Study of Pembrolizumab (MK-3475) Versus Investigator's Ch... | NCT02564263

ID	Type	Description
163145	Registry Identifier	JAPAN-CTI
MK-3475-181	Other Identifier	Merck
KEYNOTE-181	Other Identifier	Merck
2015-002782-32	EudraCT Number

Label	Type	Description	Intervention Names
Pembrolizumab	Experimental	Participants received pembrolizumab 200 mg, intravenously (IV) on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).	Biological: pembrolizumab
Chemotherapy	Active Comparator	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).	Drug: paclitaxel Drug: docetaxel Drug: irinotecan

Name	Type	Description	Arm Group Labels	Other Names
pembrolizumab	Biological	200 mg administered as IV infusion on Day 1 of every 21-day cycle	Pembrolizumab

Measure	Description	Time Frame
Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus	OS was defined as the time from randomization to death due to any cause. Median OS in participants with SCC of the esophagus is presented.	Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)	OS was defined as the time from randomization to death due to any cause. Median OS in participants with a PD-L1 CPS ≥10 is presented.	Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
Overall Survival (OS) in All Participants	OS was defined as the time from randomization to death due to any cause. Median OS in all participants is presented.	Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)

Measure	Description	Time Frame
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS as assessed by blinded independent central review per RECIST 1.1 in all participants is presented.

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

PubMed Identifier	Type	Citation	Retractions
33026938	Result	Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, Doi T, Moriwaki T, Kim SB, Lee SH, Bennouna J, Kato K, Shen L, Enzinger P, Qin SK, Ferreira P, Chen J, Girotto G, de la Fouchardiere C, Senellart H, Al-Rajabi R, Lordick F, Wang R, Suryawanshi S, Bhagia P, Kang SP, Metges JP; KEYNOTE-181 Investigators. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020 Dec 10;38(35):4138-4148. doi: 10.1200/JCO.20.01888. Epub 2020 Oct 7.
34730989

Label	URL
Merck Oncology Clinical Trial Information	View source

ID	Title	Description
FG000	Pembrolizumab	Participants received pembrolizumab 200 mg, intravenously (IV) on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
FG001	Chemotherapy

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 25, 2021	Feb 9, 2023

ID	Title	Description
BG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
BG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000314 BG001314 BG002628

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

Primary

Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus

OS was defined as the time from randomization to death due to any cause. Median OS in participants with SCC of the esophagus is presented.

The efficacy analysis population consisted of all randomized participants with SCC of the esophagus. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
OG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).

Units	Counts
Participants	OG000198 OG001203

Title

Denominators

Categories

Title	Measurements
	OG0008.2(6.7 to 10.3) OG0017.1(6.1 to 8.2)

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		0.00894	One-sided p-value based on stratified log-rank test	Hazard Ratio (HR)	0.77			2-Sided	95	0.63	0.96			Cox regression model with treatment as a covariate stratified by geographic region (Asia vs RoW)		Superiority

Primary

Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

OS was defined as the time from randomization to death due to any cause. Median OS in participants with a PD-L1 CPS ≥10 is presented.

The efficacy analysis population consisted of all randomized participants with a PD-L1 CPS ≥10. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
OG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).

Units	Counts
Participants

Primary

Overall Survival (OS) in All Participants

OS was defined as the time from randomization to death due to any cause. Median OS in all participants is presented.

The efficacy analysis population consisted of all randomized participants. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
OG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).

Units	Counts
Participants

Secondary

Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS as assessed by blinded independent central review per RECIST 1.1 in all participants is presented.

The efficacy analysis population consisted of all randomized participants. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
OG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).

Secondary

Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants

ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. The percentage of all participants who experienced a CR or PR is presented.

The efficacy analysis population consisted of all randomized participants. Participants were included in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
OG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).

Secondary

Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus

The efficacy analysis population consisted of all randomized participants with SCC of the esophagus. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
OG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).

Secondary

Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

The efficacy analysis population consisted of all randomized participants with a PD-L1 CPS ≥10. Participants were included in the treatment group to which they were randomized.

Posted

Median

95% Confidence Interval

Months

Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
OG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).

Secondary

Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus

ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. The percentage of participants with SCC of the esophagus who experienced a CR or PR is presented.

The efficacy analysis population consisted of all randomized participants with SCC of the esophagus. Participants were included in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
OG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).

Secondary

Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)

ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. The percentage of participants with a PD-L1 CPS ≥10 who experienced a CR or PR is presented.

The efficacy analysis population consisted of all randomized participants with a PD-L1 CPS ≥10. Participants were included in the treatment group to which they were randomized.

Posted

Number

95% Confidence Interval

Percentage of Participants

Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
OG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).

Secondary

Number of Participants Experiencing an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who experienced ≥1 AE is presented.

The analysis population consisted of all randomized participants who received at least 1 dose of study treatment. Participants were included in the treatment group to which they were randomized.

Posted

Count of Participants

Participants

Through End-of-Trial Analysis data cutoff date of 14-Mar-2022 (up to approximately 6 years)

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
OG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).

Secondary

Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE)

The analysis population consisted of all randomized participants who received at least 1 dose of study treatment. Participants were included in the treatment group to which they were randomized.

Posted

Count of Participants

Participants

Through End-of-Trial Analysis data cutoff date of 14-Mar-2022 (up to approximately 6 years)

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg IV on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).
OG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0015 events5 affected296 at risk EG0020 events0 affected5 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG00124 events22 affected296 at risk EG0020 events0 affected5 at risk
Immune thrombocytopenia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0015 events4 affected296 at risk EG0020 events0 affected5 at risk
Acute left ventricular failure	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0003 events2 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Myocarditis	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Tachycardia	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Tracheo-oesophageal fistula	Congenital, familial and genetic disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Hypercalcaemia of malignancy	Endocrine disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Hypophysitis	Endocrine disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Cataract	Eye disorders	MedDRA 24.1	Systematic Assessment	EG0002 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0003 events3 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Colitis	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0003 events3 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Constipation	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0014 events4 affected296 at risk EG0020 events0 affected5 at risk
Diverticulum oesophageal	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG00012 events11 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0014 events4 affected296 at risk EG0020 events0 affected5 at risk
Gastrointestinal hypomotility	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Intestinal perforation	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0013 events3 affected296 at risk EG0020 events0 affected5 at risk
Oesophageal fistula	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Oesophageal haemorrhage	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0004 events4 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Oesophageal obstruction	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0003 events3 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Oesophageal perforation	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Oesophageal stenosis	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Oesophageal ulcer	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Peritoneal adhesions	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0013 events3 affected296 at risk EG0020 events0 affected5 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0015 events5 affected296 at risk EG0020 events0 affected5 at risk
Asthenia	General disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Chest pain	General disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Death	General disorders	MedDRA 24.1	Systematic Assessment	EG0005 events5 affected314 at risk EG00110 events10 affected296 at risk EG0020 events0 affected5 at risk
Fatigue	General disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
General physical health deterioration	General disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Pyrexia	General disorders	MedDRA 24.1	Systematic Assessment	EG0004 events4 affected314 at risk EG0014 events4 affected296 at risk EG0020 events0 affected5 at risk
Strangulated hernia	General disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 24.1	Systematic Assessment	EG0003 events3 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Liver injury	Hepatobiliary disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Appendicitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
Bacteraemia	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Beta haemolytic streptococcal infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Bronchitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
Candida infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Cellulitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Device related sepsis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Empyema	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Hepatic infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Herpes zoster	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
Infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
Liver abscess	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Lower respiratory tract infection viral	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Mediastinitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Peritonitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Pneumonia	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG00015 events14 affected314 at risk EG00126 events22 affected296 at risk EG0020 events0 affected5 at risk
Pneumonia aspiration	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG00013 events12 affected314 at risk EG0015 events5 affected296 at risk EG0020 events0 affected5 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
Pneumonia necrotising	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Pulmonary sepsis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Respiratory tract infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0003 events3 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
Sepsis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0004 events4 affected314 at risk EG0014 events3 affected296 at risk EG0020 events0 affected5 at risk
Septic shock	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Stoma site infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Tracheitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Tracheostomy infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Urinary tract infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Varicella zoster virus infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Vascular device infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Anastomotic fistula	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Anastomotic leak	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Foreign body in gastrointestinal tract	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Gastrostomy failure	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Radiation pneumonitis	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Tracheal injury	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Tracheal obstruction	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Hepatic enzyme increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Liver function test increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Neutrophil count decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0013 events3 affected296 at risk EG0020 events0 affected5 at risk
Weight decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
White blood cell count decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
White blood cell count increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0014 events4 affected296 at risk EG0020 events0 affected5 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0003 events3 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Type 1 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Fistula inflammation	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Polymyositis	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Head and neck cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Bell's palsy	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Cerebellar stroke	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Cerebral infarction	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Demyelination	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Dyskinesia	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Dystonia	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Facial paralysis	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Guillain-Barre syndrome	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Haemorrhagic stroke	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Headache	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Hemiparesis	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Neuralgia	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Radiculopathy	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Spinal cord compression	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Vocal cord paralysis	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Device dislocation	Product Issues	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Device occlusion	Product Issues	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Completed suicide	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Confusional state	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Delirium	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Prostatitis	Reproductive system and breast disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0010 events0 affected296 at risk EG0021 events1 affected5 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0002 events1 affected314 at risk EG0012 events2 affected296 at risk EG0020 events0 affected5 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0007 events7 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0003 events3 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Pulmonary necrosis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Stridor	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Tracheal fistula	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Upper airway obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Dermal cyst	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0020 events0 affected5 at risk
Haemorrhage	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk
Shock haemorrhagic	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0020 events0 affected5 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG00060 events52 affected314 at risk EG001110 events83 affected296 at risk EG0022 events1 affected5 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG00165 events36 affected296 at risk EG0020 events0 affected5 at risk
Hypothyroidism	Endocrine disorders	MedDRA 24.1	Systematic Assessment	EG00040 events37 affected314 at risk EG0017 events7 affected296 at risk EG0021 events1 affected5 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0007 events7 affected314 at risk EG0012 events2 affected296 at risk EG0021 events1 affected5 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG00036 events34 affected314 at risk EG00132 events27 affected296 at risk EG0020 events0 affected5 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG00016 events14 affected314 at risk EG00119 events17 affected296 at risk EG0020 events0 affected5 at risk
Constipation	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG00063 events56 affected314 at risk EG00163 events56 affected296 at risk EG0020 events0 affected5 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG00065 events38 affected314 at risk EG001120 events79 affected296 at risk EG0021 events1 affected5 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0007 events6 affected314 at risk EG00113 events11 affected296 at risk EG0021 events1 affected5 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG00044 events40 affected314 at risk EG00127 events26 affected296 at risk EG0021 events1 affected5 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG00066 events59 affected314 at risk EG001110 events83 affected296 at risk EG0020 events0 affected5 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0009 events9 affected314 at risk EG00130 events28 affected296 at risk EG0020 events0 affected5 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG00045 events37 affected314 at risk EG00174 events53 affected296 at risk EG0020 events0 affected5 at risk
Asthenia	General disorders	MedDRA 24.1	Systematic Assessment	EG00048 events45 affected314 at risk EG00158 events43 affected296 at risk EG0020 events0 affected5 at risk
Fatigue	General disorders	MedDRA 24.1	Systematic Assessment	EG00070 events67 affected314 at risk EG001121 events87 affected296 at risk EG0020 events0 affected5 at risk
Malaise	General disorders	MedDRA 24.1	Systematic Assessment	EG00018 events15 affected314 at risk EG00126 events19 affected296 at risk EG0020 events0 affected5 at risk
Oedema peripheral	General disorders	MedDRA 24.1	Systematic Assessment	EG00020 events19 affected314 at risk EG00119 events19 affected296 at risk EG0020 events0 affected5 at risk
Pyrexia	General disorders	MedDRA 24.1	Systematic Assessment	EG00041 events31 affected314 at risk EG00158 events45 affected296 at risk EG0020 events0 affected5 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG00017 events12 affected314 at risk EG00115 events13 affected296 at risk EG0022 events1 affected5 at risk
Alanine aminotransferase increased	Investigations	MedDRA 24.1	Systematic Assessment	EG00026 events22 affected314 at risk EG00116 events10 affected296 at risk EG0020 events0 affected5 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 24.1	Systematic Assessment	EG00033 events26 affected314 at risk EG00116 events14 affected296 at risk EG0021 events1 affected5 at risk
Blood creatinine increased	Investigations	MedDRA 24.1	Systematic Assessment	EG00011 events8 affected314 at risk EG0014 events3 affected296 at risk EG0021 events1 affected5 at risk
Blood sodium decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0021 events1 affected5 at risk
Blood thyroid stimulating hormone increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0004 events3 affected314 at risk EG0013 events3 affected296 at risk EG0021 events1 affected5 at risk
Lymphocyte count decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG00010 events9 affected314 at risk EG00115 events9 affected296 at risk EG0021 events1 affected5 at risk
Neutrophil count decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected314 at risk EG001113 events50 affected296 at risk EG0020 events0 affected5 at risk
Weight decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG00039 events39 affected314 at risk EG00143 events34 affected296 at risk EG0021 events1 affected5 at risk
White blood cell count decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG001114 events52 affected296 at risk EG0020 events0 affected5 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG00082 events76 affected314 at risk EG00197 events76 affected296 at risk EG0021 events1 affected5 at risk
Gout	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0010 events0 affected296 at risk EG0021 events1 affected5 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG00021 events16 affected314 at risk EG00114 events14 affected296 at risk EG0020 events0 affected5 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG00013 events8 affected314 at risk EG0017 events6 affected296 at risk EG0021 events1 affected5 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG00023 events17 affected314 at risk EG00116 events15 affected296 at risk EG0020 events0 affected5 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG00015 events15 affected314 at risk EG00140 events29 affected296 at risk EG0020 events0 affected5 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG00027 events19 affected314 at risk EG00124 events17 affected296 at risk EG0020 events0 affected5 at risk
Iron deficiency	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected314 at risk EG0011 events1 affected296 at risk EG0021 events1 affected5 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG00026 events24 affected314 at risk EG00122 events19 affected296 at risk EG0020 events0 affected5 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG00040 events38 affected314 at risk EG00127 events24 affected296 at risk EG0020 events0 affected5 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG00010 events8 affected314 at risk EG00131 events25 affected296 at risk EG0020 events0 affected5 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG00010 events8 affected314 at risk EG0019 events8 affected296 at risk EG0021 events1 affected5 at risk
Dementia Alzheimer's type	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0010 events0 affected296 at risk EG0021 events1 affected5 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0007 events6 affected314 at risk EG00128 events25 affected296 at risk EG0020 events0 affected5 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0003 events3 affected314 at risk EG00153 events52 affected296 at risk EG0020 events0 affected5 at risk
Insomnia	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG00025 events25 affected314 at risk EG00142 events16 affected296 at risk EG0020 events0 affected5 at risk
Irritability	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected314 at risk EG0011 events1 affected296 at risk EG0021 events1 affected5 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG00046 events40 affected314 at risk EG00133 events30 affected296 at risk EG0020 events0 affected5 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG00036 events31 affected314 at risk EG00121 events17 affected296 at risk EG0020 events0 affected5 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG0004 events4 affected314 at risk EG00188 events88 affected296 at risk EG0020 events0 affected5 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG00027 events23 affected314 at risk EG0018 events8 affected296 at risk EG0021 events1 affected5 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG00024 events20 affected314 at risk EG00127 events25 affected296 at risk EG0020 events0 affected5 at risk

ID	Term
D004938	Esophageal Neoplasms
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D006258	Head and Neck Neoplasms
D004066	Digestive System Diseases
D004935	Esophageal Diseases
D005767	Gastrointestinal Diseases

ID	Term
C582435	pembrolizumab
D017239	Paclitaxel
D000077143	Docetaxel
D000077146	Irinotecan

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D004224	Diterpenes
D013729	Terpenes
D002166	Camptothecin
D000470	Alkaloids
D006571	Heterocyclic Compounds

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pembrolizumab First Course	Participants received pembrolizumab 200 mg, intravenously (IV) on Day 1 of every 21-day (3-week) cycle for up to 35 administrations (up to approximately 25 months).	305	314	127	314	285	314
EG001	Chemotherapy	Participants received Investigator's choice of paclitaxel 80-100 mg/m^2 IV on Days 1, 8, and 15 of every 28-day (4-week) cycle, OR docetaxel 75 mg/m^2 IV on Day 1 of every 21-day (3-week) cycle, OR irinotecan 180 mg/m^2 IV on Day 1 of every 14-day (2-week) cycle (up to approximately 19 months).	305	314	121	296	281	296
EG002	Pembrolizumab Second Course	Qualified participants who received pembrolizumab as a first course and stopped the first course of pembrolizumab due to complete response (CR) or completed the first course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional).	3	5	1	5	5	5