Study of Pembrolizumab (MK-3475) or Placebo With Chemorad... | NCT03040999

NCT03040999

ID	Type	Description
MK-3475-412	Other Identifier	MSD
173640	Registry Identifier	JAPIC-CTI
KEYNOTE-412	Other Identifier	MSD
2016-003934-25	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pembrolizumab + Cisplatin + CRT	Experimental	Participants receive a priming dose of pembrolizumab before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with pembrolizumab.	Biological: Pembrolizumab Drug: Cisplatin Radiation: Accelerated Fractionation (AFX) Radiotherapy Radiation: Standard Fractionation (SFX) Radiotherapy
Placebo + Cisplatin + CRT	Placebo Comparator	Participants receive placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with placebo.	Drug: Placebo Drug: Cisplatin Radiation: Accelerated Fractionation (AFX) Radiotherapy Radiation: Standard Fractionation (SFX) Radiotherapy

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	Administered as an intravenous (IV) infusion every 3 weeks (Q3W)	Pembrolizumab + Cisplatin + CRT

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Event-free Survival (EFS)	EFS was defined as the time from date of randomization to the date of first record of any of the following events: death due to any cause; progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR) or biopsy as indicated for locoregional progression or recurrence or distant metastasis. As well as the first record of the following types of surgery: salvage surgery for persistent or residual disease at the primary tumor site requiring surgical removal when invasive cancer is present on final pathology; neck dissection or surgery (performed for clinical or radiological disease progression per RECIST 1.1) ≤ 20 weeks from end of CRT when invasive cancer is present; or neck dissection or surgery >20 weeks from end of CRT when invasive cancer is present. The non-parametric Kaplan-Meier method was used to estimate the EFS curve in each treatment group.	Up to approximately 62 months

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the time from the date of randomization to the date of death due to any cause. Participants without documented death at the time of analysis were censored at the date the participant was last known to be alive. The non-parametric Kaplan-Meier method was used to estimate the survival curve in each treatment group.	Up to approximately 62 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has a pathologically proven new diagnosis of oropharyngeal p16 positive, oropharyngeal p16 negative, or larynx/hypopharynx/oral cavity (independent of p16) squamous cell carcinoma. Participants with oral cavity tumors need to have unresectable disease. Participants with multiple synchronous tumors are not eligible for the study.
Has provided tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker analysis from a core or excisional biopsy. If an excisional or incisional biopsy has been performed, participants remain eligible for the study provided the residual disease meets the staging criteria required for the trial (e.g., excisional biopsy of a lymph node with residual T4 primary). Prior surgical debulking, including tonsillectomy, for the head and neck cancer under study is not allowed.
Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan or magnetic resonance imaging, based on RECIST version 1.1
Is eligible for definitive CRT and not considered for primary surgery based on investigator decision
Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days prior to receiving the first dose of study therapy
Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 180 days after the last dose of study therapy

Exclusion Criteria:

Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy
Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in clinical studies with pembrolizumab
Has received a live vaccine within 30 days prior to the first dose of study therapy
Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer
Has had prior systemic therapy, targeted therapy, radiotherapy treatment or radical surgery for head and neck cancer under study
Has not recovered from major surgery prior to starting study therapy
Has known active Hepatitis B or C
Has known history of Human Immunodeficiency Virus (HIV)
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has had previous allogeneic tissue/solid organ transplant
Has active infection requiring systemic therapy
Has a history of severe hypersensitivity reaction to pembrolizumab, Cisplatin or radiotherapy or their analogs
Is pregnant or breast feeding or expecting to conceive or father children throughout the study period and for up to 180 days after the last dose of study therapy

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
UCLA Medical Center ( Site 0273)		Los Angeles	California	90095	United States
University of California San Francisco ( Site 0274)

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38561010	Derived	Machiels JP, Tao Y, Licitra L, Burtness B, Tahara M, Rischin D, Alves G, Lima IPF, Hughes BGM, Pointreau Y, Aksoy S, Laban S, Greil R, Burian M, Hetnal M, Delord JP, Mesia R, Taberna M, Waldron JN, Simon C, Gregoire V, Harrington KJ, Swaby RF, Zhang Y, Gumuscu B, Bidadi B, Siu LL; KEYNOTE-412 Investigators. Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2024 May;25(5):572-587. doi: 10.1016/S1470-2045(24)00100-1. Epub 2024 Mar 29.
32490686

Label	URL
Merck Clinical Trial Information	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Nov 21, 2022

Arm/Group Information

ID	Title	Description
BG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.
BG001	Placebo + CRT + Placebo	On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00058.8± 9.0 BG00158.6± 7.8 BG00258.7± 8.4

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00071 BG00173 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00047 BG00159 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0002 BG0010 BG002

Human Papilloma Virus (HPV) Status

Participants were assessed for HPV status using immunohistochemistry (IHC) analysis with CINtec® p16 histology assay. Positive p16 expression was defined as a strong and diffuse nuclear and cytoplasmic staining in 70% or more of the tumor cells.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Positive	BG000109 BG001

Disease stage at baseline

Disease status at baseline was done using the American Joint Committee on Cancer (AJCC) Staging manual for head and neck cancers. AJCC7 for patients enrolled before Jan 1, 2018, and AJCC8 for those enrolled on or after Jan 1, 2018. Stages progress from best (II) to worst prognosis (IVb). Stage II: Large tumor size and/or limited local spread; Stage III: Large tumor size and/or limited local spread and/or spread to neck lymph nodes (NLNs); Stage IVa: Moderately advanced locally and/or spread to NLNs; Stage IVb: Very advanced locally and/or spread to NLNs with extranodal extension.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
AJCC7 III	BG0008 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Secondary

Overall Survival (OS)

OS was defined as the time from the date of randomization to the date of death due to any cause. Participants without documented death at the time of analysis were censored at the date the participant was last known to be alive. The non-parametric Kaplan-Meier method was used to estimate the survival curve in each treatment group.

All randomized participants based on the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Up to approximately 62 months

ID	Title	Description
OG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.
OG001	Placebo + CRT + Placebo	On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.

Units	Counts
Participants	OG000402 OG001402

Title

Denominators

Categories

Title	Measurements
	OG000NA(NA to NA)NA = median, upper limit, and lower limit were not reached due to insufficient number of participants with an event. OG001NA(NA to NA)NA = median, upper limit, and lower limit were not reached due to insufficient number of participants with an event.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank	One-sided p-value based on log-rank test stratified by human papilloma virus (HPV) status and overall cancer stage.	0.1997		Hazard Ratio (HR)	0.90			2-Sided	95	0.71	1.15			Based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by HPV status and overall cancer stage.		Superiority

Secondary

Number of Participants Who Experienced an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy. The number of participants who experienced an AE is presented.

All randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Up to approximately 88 months

ID	Title	Description
OG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.
OG001	Placebo + CRT + Placebo

Secondary

Number of Participants Who Discontinued Study Drug Due to an AE

All randomized participants who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Up to approximately 15 months

ID	Title	Description
OG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.
OG001	Placebo + CRT + Placebo

Secondary

Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) Score

The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of cancer patients. For Global Health Status (GHS) (Item 29), participants are asked "How would you rate your overall health during the past week?" Individual items are scored on a 7-point (1=very poor to 7=excellent). Raw scores for each scale are standardized into a range of 0 to 100 by linear transformation, with a higher score indicating a better level of function and better overall GHS. A change from baseline of 10 points on the 100-point EORTC QLQ-C30 scale is considered as clinically relevant. Analysis based on a constrained longitudinal data analysis (cLDA) model with the patient reported outcomes (PRO) scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of human papilloma virus (HPV) status and overall cancer stage.

Participants with at least one patient reported outcome (PRO) assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a scale

Baseline and up to week 45

ID	Title	Description
OG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.

Secondary

Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Questionnaire (EORTC QLQ-H&N35) Swallowing Score

EORTC QLQ Head and Neck Questionnaire (H&N35) measures QoL in head and neck cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in swallowing was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a scale

Baseline and up to Week 45

ID	Title	Description
OG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.

Secondary

Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Questionnaire (EORTC QLQ-H&N35) Speech Score

EORTC QLQ Head and Neck Questionnaire (H&N35) measures QoL in head and neck cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the speech scale (Items 30-32) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in speech was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a scale

Baseline and up to Week 45

ID	Title	Description
OG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.

Secondary

Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Questionnaire (EORTC QLQ-H&N35) Pain Symptom Score

EORTC QLQ Head and Neck Questionnaire (H&N35) measures QoL in head and Neck Cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in pain symptoms was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a scale

Baseline and up to Week 45

ID	Title	Description
OG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.

Secondary

Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning Score

The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of cancer patients. Participant responded to 5 questions from the EORTC QLQ-C30 about their physical functioning scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100, where a higher score indicates a better physical functioning. A change from baseline of 10 points on the 100-point scale is considered as clinically relevant. Analysis was based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

Participants with at least one PRO assessment available for this specific endpoint and who had received at least 1 dose of study intervention.

Posted

Least Squares Mean

95% Confidence Interval

Scores on a scale

Baseline and up to Week 45

ID	Title	Description
OG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.

Primary

Event-free Survival (EFS)

EFS was defined as the time from date of randomization to the date of first record of any of the following events: death due to any cause; progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR) or biopsy as indicated for locoregional progression or recurrence or distant metastasis. As well as the first record of the following types of surgery: salvage surgery for persistent or residual disease at the primary tumor site requiring surgical removal when invasive cancer is present on final pathology; neck dissection or surgery (performed for clinical or radiological disease progression per RECIST 1.1) ≤ 20 weeks from end of CRT when invasive cancer is present; or neck dissection or surgery >20 weeks from end of CRT when invasive cancer is present. The non-parametric Kaplan-Meier method was used to estimate the EFS curve in each treatment group.

All randomized participants based on the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Up to approximately 62 months

ID	Title	Description
OG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pembrolizumab + CRT + Pembrolizumab	On Cycle 1 Day 1 (each cycle is 21 days), participants received a priming dose of 200 mg Pembrolizumab followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of pembrolizumab (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with pembrolizumab.	156	402	245	398	398	398
EG001	Placebo + CRT + Placebo	On Cycle 1 Day 1 (each cycle is 21 days), participants received placebo followed by 100 mg/m^2 Cisplatin PLUS 70 Gray (Gy) Radiotherapy (accelerated (AFX) or standard fractionation radiotherapy (SFX)) on Day 8 of Cycles 1, 2 and Cycle 3 (SFX RT regimen only). During CRT, participants received 2 doses of placebo (Day 1 of Cycles 2 and 3) and up to 3 cycles of Cisplatin (2 cycles during AFX and 3 cycles during SFX RT). Participants also received up to an additional 14 cycles of placebo alone as maintenance therapy for a total of 17 cycles of placebo (approximately 1 year). If cisplatin and/or radiation therapy was discontinued, the participant may continue on treatment with placebo.	178	402	197	398	396	398

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Agranulocytosis	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0005 events4 affected398 at risk EG0011 events1 affected398 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG00026 events24 affected398 at risk EG0017 events7 affected398 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Lymphadenitis	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0013 events3 affected398 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Cardiac arrest	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0010 events0 affected398 at risk
Cardiac failure	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Sinus node dysfunction	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Hypophysitis	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Eyelid ptosis	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Vitreous detachment	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Achlorhydria	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Colitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected398 at risk EG0011 events1 affected398 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected398 at risk EG0012 events2 affected398 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected398 at risk EG0014 events4 affected398 at risk
Duodenal perforation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00011 events11 affected398 at risk EG00113 events12 affected398 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected398 at risk EG0010 events0 affected398 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Gastric perforation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events2 affected398 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Gastric ulcer perforation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Haematochezia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected398 at risk EG0016 events5 affected398 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00019 events17 affected398 at risk EG0018 events7 affected398 at risk
Neutropenic colitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected398 at risk EG0010 events0 affected398 at risk
Oesophageal obstruction	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Oesophageal stenosis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected398 at risk EG0010 events0 affected398 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Pneumatosis intestinalis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Salivary hypersecretion	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Small intestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected398 at risk EG0010 events0 affected398 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00012 events12 affected398 at risk EG00113 events12 affected398 at risk
Tongue oedema	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events2 affected398 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00017 events15 affected398 at risk EG00111 events10 affected398 at risk
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0013 events3 affected398 at risk
Chest pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Complication associated with device	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Condition aggravated	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Death	General disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected398 at risk EG0018 events8 affected398 at risk
Face oedema	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Facial pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0014 events4 affected398 at risk
Fibrosis	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
General physical health deterioration	General disorders	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected398 at risk EG0013 events3 affected398 at risk
Impaired healing	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Malaise	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0013 events3 affected398 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG00010 events10 affected398 at risk EG0019 events9 affected398 at risk
Swelling	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Vascular device occlusion	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Vascular stent thrombosis	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Cholangitis sclerosing	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0010 events0 affected398 at risk
Hepatitis fulminant	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0010 events0 affected398 at risk
Hypersensitivity	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0010 events0 affected398 at risk
Abdominal abscess	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Abscess jaw	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Abscess neck	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0011 events1 affected398 at risk
Appendicitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Arthritis infective	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Bacteraemia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events2 affected398 at risk
Bacterial sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Bronchitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0005 events4 affected398 at risk EG0013 events3 affected398 at risk
Bronchitis bacterial	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Candida sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Catheter site abscess	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Catheter site infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Cellulitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected398 at risk EG0013 events3 affected398 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0011 events1 affected398 at risk
Dermatitis infected	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Device related infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0011 events1 affected398 at risk
Device related sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Empyema	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Epiglottitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Erysipelas	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Fungaemia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Gangrene	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Gastroenteritis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Genitourinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Hepatitis B reactivation	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Herpes zoster	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Infected fistula	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Infectious pleural effusion	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Intervertebral discitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Laryngitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Lung abscess	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Mediastinitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Meningitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Meningitis aseptic	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Neutropenic sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Ophthalmic herpes zoster	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Oral bacterial infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Oral candidiasis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events2 affected398 at risk
Otitis media	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Parotitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Pharyngitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00049 events43 affected398 at risk EG00133 events25 affected398 at risk
Pneumonia aspiration	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00012 events12 affected398 at risk EG0016 events5 affected398 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Post procedural infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events1 affected398 at risk
Respiratory syncytial virus bronchitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected398 at risk EG0011 events1 affected398 at risk
Sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00012 events12 affected398 at risk EG0017 events7 affected398 at risk
Septic shock	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected398 at risk EG0012 events2 affected398 at risk
Skin bacterial infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Staphylococcal infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events2 affected398 at risk
Stoma site cellulitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Stoma site infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0012 events2 affected398 at risk
Streptococcal bacteraemia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Systemic infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0010 events0 affected398 at risk
Tracheitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0013 events2 affected398 at risk
Tracheobronchitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Tracheostomy infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Tuberculosis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected398 at risk EG0011 events1 affected398 at risk
Urosepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected398 at risk EG0010 events0 affected398 at risk
Vascular access site infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events2 affected398 at risk
Vascular device infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0011 events1 affected398 at risk
Viral infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Wound infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0010 events0 affected398 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0014 events2 affected398 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Arterial injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Chest injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Gastrostomy failure	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Gastrostomy tube site complication	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Osteoradionecrosis	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0012 events2 affected398 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Radiation associated pain	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Radiation necrosis	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events2 affected398 at risk
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Stoma complication	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Tracheal obstruction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events1 affected398 at risk
Tracheostomy malfunction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Unintentional medical device removal	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Vascular pseudoaneurysm	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0010 events0 affected398 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected398 at risk EG0010 events0 affected398 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Blood bilirubin increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Blood creatinine increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0004 events3 affected398 at risk EG0013 events2 affected398 at risk
C-reactive protein increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events2 affected398 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Lipase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Neutrophil count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected398 at risk EG0015 events5 affected398 at risk
Platelet count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0012 events2 affected398 at risk
Weight decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected398 at risk EG0012 events2 affected398 at risk
White blood cell count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected398 at risk EG0019 events7 affected398 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected398 at risk EG0015 events5 affected398 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00010 events9 affected398 at risk EG0016 events5 affected398 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0011 events1 affected398 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected398 at risk EG0013 events3 affected398 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00010 events10 affected398 at risk EG0013 events3 affected398 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0011 events1 affected398 at risk
Latent autoimmune diabetes in adults	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected398 at risk EG0011 events1 affected398 at risk
Tumour lysis syndrome	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Type 1 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events2 affected398 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Joint effusion	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Trismus	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events2 affected398 at risk
Follicular lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Follicular thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Infected neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Lip and/or oral cavity cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Neoplasm swelling	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Neuroendocrine carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Oesophageal squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Rectal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected398 at risk EG0011 events1 affected398 at risk
Tumour inflammation	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Cerebral venous sinus thrombosis	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0010 events0 affected398 at risk
Epilepsy	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Syncope	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected398 at risk EG0014 events2 affected398 at risk
Vocal cord paralysis	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Device breakage	Product Issues	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Device dislocation	Product Issues	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Alcohol abuse	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Alcohol withdrawal syndrome	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Alcoholism	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Confusional state	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Delirium	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0013 events3 affected398 at risk
Depression	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Drug abuse	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Insomnia	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Panic attack	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG00041 events33 affected398 at risk EG00133 events30 affected398 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0015 events5 affected398 at risk
Dysuria	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
End stage renal disease	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Renal injury	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Tubulointerstitial nephritis	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0012 events2 affected398 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0012 events2 affected398 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0010 events0 affected398 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected398 at risk EG0012 events2 affected398 at risk
Epiglottic oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Laryngeal cyst	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Laryngeal fistula	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Laryngeal haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Laryngeal necrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0009 events9 affected398 at risk EG0015 events5 affected398 at risk
Oropharyngeal fistula	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0013 events2 affected398 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Pharyngeal haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected398 at risk EG0015 events3 affected398 at risk
Pharyngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected398 at risk EG0014 events4 affected398 at risk
Pharyngeal necrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Pharyngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Pharyngeal swelling	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Pharyngeal ulceration	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0011 events1 affected398 at risk
Pneumonia lipoid	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00011 events10 affected398 at risk EG0013 events3 affected398 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected398 at risk EG0012 events2 affected398 at risk
Respiratory acidosis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected398 at risk EG0010 events0 affected398 at risk
Stridor	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0013 events2 affected398 at risk
Tracheal stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Drug reaction with eosinophilia and systemic symptoms	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Pemphigoid	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Haemorrhage	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Hypotension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Jugular vein thrombosis	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected398 at risk EG0010 events0 affected398 at risk
Peripheral artery thrombosis	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Phlebitis	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk
Venous thrombosis limb	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected398 at risk EG0011 events1 affected398 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG000298 events229 affected398 at risk EG001287 events205 affected398 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG00029 events28 affected398 at risk EG00135 events33 affected398 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG00084 events80 affected398 at risk EG00151 events49 affected398 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG00083 events75 affected398 at risk EG00192 events88 affected398 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG00043 events40 affected398 at risk EG00135 events33 affected398 at risk
Hypothyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG000110 events100 affected398 at risk EG00158 events54 affected398 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00023 events22 affected398 at risk EG00113 events13 affected398 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG000218 events179 affected398 at risk EG001213 events174 affected398 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG000121 events88 affected398 at risk EG001106 events82 affected398 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG000206 events191 affected398 at risk EG001194 events173 affected398 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00034 events26 affected398 at risk EG00126 events25 affected398 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG000190 events177 affected398 at risk EG001185 events165 affected398 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00031 events30 affected398 at risk EG00121 events19 affected398 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG000324 events222 affected398 at risk EG001337 events232 affected398 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00096 events87 affected398 at risk EG00198 events89 affected398 at risk
Oral pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00030 events28 affected398 at risk EG00123 events22 affected398 at risk
Saliva altered	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00023 events22 affected398 at risk EG00126 events26 affected398 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG000279 events249 affected398 at risk EG001259 events232 affected398 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG000204 events131 affected398 at risk EG001168 events116 affected398 at risk
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG00093 events74 affected398 at risk EG00189 events73 affected398 at risk
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG000150 events126 affected398 at risk EG001137 events118 affected398 at risk
Localised oedema	General disorders	MedDRA 27.0	Systematic Assessment	EG00029 events26 affected398 at risk EG00129 events28 affected398 at risk
Oedema peripheral	General disorders	MedDRA 27.0	Systematic Assessment	EG00026 events21 affected398 at risk EG00120 events18 affected398 at risk
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG00094 events64 affected398 at risk EG00155 events43 affected398 at risk
Nasopharyngitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00015 events14 affected398 at risk EG00120 events20 affected398 at risk
Oral candidiasis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00085 events77 affected398 at risk EG00171 events60 affected398 at risk
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00025 events23 affected398 at risk EG00123 events21 affected398 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG00035 events26 affected398 at risk EG00121 events17 affected398 at risk
Radiation skin injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG000260 events254 affected398 at risk EG001244 events242 affected398 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG000100 events79 affected398 at risk EG00174 events60 affected398 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00078 events59 affected398 at risk EG00149 events41 affected398 at risk
Blood creatinine increased	Investigations	MedDRA 27.0	Systematic Assessment	EG000128 events92 affected398 at risk EG001129 events87 affected398 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00061 events47 affected398 at risk EG00140 events36 affected398 at risk
Lymphocyte count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG000143 events95 affected398 at risk EG001147 events109 affected398 at risk
Neutrophil count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG000228 events166 affected398 at risk EG001240 events152 affected398 at risk
Platelet count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG000150 events97 affected398 at risk EG001120 events83 affected398 at risk
Weight decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG000192 events179 affected398 at risk EG001201 events183 affected398 at risk
White blood cell count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG000224 events127 affected398 at risk EG001236 events135 affected398 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG000115 events104 affected398 at risk EG001126 events115 affected398 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00049 events44 affected398 at risk EG00148 events38 affected398 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00044 events31 affected398 at risk EG00151 events35 affected398 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00038 events27 affected398 at risk EG00152 events36 affected398 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00041 events31 affected398 at risk EG00150 events33 affected398 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00051 events41 affected398 at risk EG00141 events33 affected398 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00048 events38 affected398 at risk EG00142 events31 affected398 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG000142 events100 affected398 at risk EG001108 events74 affected398 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG000163 events110 affected398 at risk EG001144 events96 affected398 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG000109 events79 affected398 at risk EG001109 events71 affected398 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00033 events30 affected398 at risk EG00132 events19 affected398 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00034 events25 affected398 at risk EG00134 events28 affected398 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00026 events21 affected398 at risk EG00114 events14 affected398 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00038 events35 affected398 at risk EG00138 events36 affected398 at risk
Trismus	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00014 events12 affected398 at risk EG00125 events23 affected398 at risk
Dizziness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00042 events30 affected398 at risk EG00128 events24 affected398 at risk
Dysgeusia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG000137 events132 affected398 at risk EG001139 events134 affected398 at risk
Headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00046 events39 affected398 at risk EG00154 events49 affected398 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00036 events34 affected398 at risk EG00142 events39 affected398 at risk
Anxiety	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG00024 events22 affected398 at risk EG00114 events14 affected398 at risk
Insomnia	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG00061 events57 affected398 at risk EG00150 events43 affected398 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG00074 events52 affected398 at risk EG00153 events39 affected398 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00075 events65 affected398 at risk EG00171 events64 affected398 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00052 events49 affected398 at risk EG00169 events62 affected398 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00024 events20 affected398 at risk EG00126 events20 affected398 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00040 events32 affected398 at risk EG00132 events25 affected398 at risk
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00010 events10 affected398 at risk EG00125 events25 affected398 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00098 events91 affected398 at risk EG00179 events72 affected398 at risk
Pharyngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00052 events51 affected398 at risk EG00148 events48 affected398 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG00045 events39 affected398 at risk EG00150 events42 affected398 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00015 events15 affected398 at risk EG00123 events22 affected398 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00018 events17 affected398 at risk EG00121 events21 affected398 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00028 events27 affected398 at risk EG00121 events19 affected398 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00057 events52 affected398 at risk EG00134 events27 affected398 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00070 events59 affected398 at risk EG00126 events24 affected398 at risk
Hypertension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG00026 events21 affected398 at risk EG00138 events33 affected398 at risk

ID	Term
D006258	Head and Neck Neoplasms
D000077195	Squamous Cell Carcinoma of Head and Neck
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D002294	Carcinoma, Squamous Cell
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type

ID	Term
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds
D013812	Therapeutics