LUX-Head&Neck 2: A Phase III Trial of Afatinib (BIBW 2992... | NCT01345669

NCT01345669

ID	Type	Description	Link
2011-000392-14	EudraCT Number	EudraCT

Status Module

Description Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Afatinib (BIBW 2992)	Experimental	Once daily	Drug: Afatinib
Placebo	Placebo Comparator	Once daily	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Once daily	Placebo
Afatinib

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Disease Free Survival (DFS)	Disease Free Survival defined as the time from randomisation until documented tumour recurrence/ second primary tumour (SPT) or death from any cause, whichever occurred first.	Up to 5 years

Secondary Outcomes

Measure	Description	Time Frame
Disease Free Survival (DFS) Rate at 2 Years	Disease Free Survival (DFS) rate at 2 years. Probability of being disease free at 2 years in percentage is provided based on Kaplan-Meier method.	Up to 2 years
Percentage of Patient Deaths (Overall Survival (OS))

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Boehringer Ingelheim	Boehringer Ingelheim	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
1200.131.00171 Boehringer Ingelheim Investigational Site		Little Rock	Arkansas		United States
1200.131.00181 Boehringer Ingelheim Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
31194247	Derived	Burtness B, Haddad R, Dinis J, Trigo J, Yokota T, de Souza Viana L, Romanov I, Vermorken J, Bourhis J, Tahara M, Martins Segalla JG, Psyrri A, Vasilevskaya I, Nangia CS, Chaves-Conde M, Kiyota N, Homma A, Holeckova P, Del Campo JM, Asarawala N, Nicolau UR, Rauch D, Even C, Wang B, Gibson N, Ehrnrooth E, Harrington K, Cohen EEW; LUX-Head & Neck 2 investigators. Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial. JAMA Oncol. 2019 Aug 1;5(8):1170-1180. doi: 10.1001/jamaoncol.2019.1146.
25432788

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Afatinib (BIBW 2992)	Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Afatinib (BIBW 2992)	Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
BG001	Placebo	Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
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
	OG00043.40(16.82 to NA)Non calculable because the 75th percentile hasn't been reached OG001NA(16.69 to NA)Non calculable because the median hasn't been reached

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	DFS was analysed using a stratified log-rank test with nodal status (N0- N2a vs. N2b-N3) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1) being the stratification factors.	Log Rank		0.4806		Hazard Ratio (HR)	1.126			2-Sided	95	0.809	1.569			Hazard ratio (Afatinib vs. Placebo) from Cox proportional hazards model stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).		Superiority or Other

Secondary

Disease Free Survival (DFS) Rate at 2 Years

Disease Free Survival (DFS) rate at 2 years. Probability of being disease free at 2 years in percentage is provided based on Kaplan-Meier method.

Randomised Set, the number of patients from the randomized set those are disease free (or DFS) at 2 years.

Posted

Number

95% Confidence Interval

Probability (%)

Up to 2 years

ID	Title	Description
OG000	Afatinib (BIBW 2992)	Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
OG001	Placebo	Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.

Units	Counts
Participants

Secondary

Percentage of Patient Deaths (Overall Survival (OS))

Overall survival (OS), defined as the time from randomisation until death (regardless of cause). Due to the small event rate in both treatment arms caused by the early termination of the trial, the hazard estimate is not interpretable. Hence presented the total randomized and the percentage of patients died.

Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised)

Posted

Number

Percentage of patients

Up to 5 years

ID	Title	Description
OG000	Afatinib (BIBW 2992)	Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
OG001	Placebo	Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.

Secondary

Patients With Improved Health Related Quality of Life (HRQOL)

HRQoL questionnaires focused on 3 scales: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Improvement was defined as a score that improved from baseline by at least 10 points (on the 0-100 point scale) at any time during the study. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the study. Patients who had neither improved nor worsened were considered as stable. Percentages of patients with improvement in HRQoL are presented.

Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised)

Posted

Number

Percentage of Patients

Up to 5 years

ID	Title	Description
OG000	Afatinib (BIBW 2992)	Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
OG001	Placebo	Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.

Secondary

Time to Deterioration in Health Related Quality of Life (HRQOL)

HRQoL questionnaires focused on 3 scales: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Time to deterioration was defined as the time from randomisation to the first 10-point worsening on the 0-100 point scale. Patients with no deterioration (including those with disease recurrence/SPT) were censored at the last available HRQoL assessment date. Patients with no post-baseline assessments were censored on the day of randomisation.

Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised)

Posted

Median

Inter-Quartile Range

Months

Up to 5 years

ID	Title	Description
OG000	Afatinib (BIBW 2992)	Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
OG001	Placebo	Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.

Secondary

Health Related Quality of Life (HRQOL) Scores Over Time

HRQoL questionnaires focused on 3 scales: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Scoring of the symptom scales/items followed the European Organisation for Research and Treatment of Cancer (EORTC) scoring manual and a linear transformation of the scores to a 0-100 point scale. Higher values are better.

Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised)

Posted

Least Squares Mean

Standard Error

Unit on Scale

Baseline and 5 years

ID	Title	Description
OG000	Afatinib (BIBW 2992)	Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
OG001	Placebo	Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.

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	Afatinib (BIBW 2992)	Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.			80	411	407	411
EG001	Placebo	Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.			51	206	169	206

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected411 at risk EG0012 affected206 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Aortic valve stenosis	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Arrhythmia	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0012 affected206 at risk
Atrial flutter	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Cardiac arrest	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0011 affected206 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Deafness neurosensory	Ear and labyrinth disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Retinal tear	Eye disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Colitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0010 affected206 at risk
Duodenal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0011 affected206 at risk
Gastric perforation	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Glossitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Intestinal haemorrhage	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Large intestine polyp	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Melaena	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0011 affected206 at risk
Pancreatitis relapsing	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Asthenia	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Death	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0011 affected206 at risk
Disease recurrence	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Fatigue	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Impaired healing	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Malaise	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Mucosal inflammation	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Non-cardiac chest pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Oedema	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Sudden death	General disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Hypersensitivity	Immune system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Sarcoidosis	Immune system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Appendicitis perforated	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Carbuncle	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Cellulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0010 affected206 at risk
Cellulitis of male external genital organ	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Diverticulitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Erysipelas	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Groin infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Hepatitis E	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Lung infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0011 affected206 at risk
Oropharyngeal candidiasis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Osteomyelitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Pneumonia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0015 affected206 at risk
Respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Septic shock	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0011 affected206 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Urethritis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Accident	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Osteoradionecrosis	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0010 affected206 at risk
Patella fracture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Post procedural complication	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Radiation fibrosis	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Radiation necrosis	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Vascular graft complication	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Blood bilirubin increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Weight decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0011 affected206 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected411 at risk EG0011 affected206 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0011 affected206 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0010 affected206 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0013 affected206 at risk
Osteonecrosis of jaw	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Scleroderma	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0011 affected206 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0003 affected411 at risk EG0010 affected206 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Metastases to lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0010 affected206 at risk
Metastases to lymph nodes	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Neoplasm recurrence	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0005 affected411 at risk EG0013 affected206 at risk
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Oropharyngeal squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0011 affected206 at risk
Recurrent cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Carotid artery thrombosis	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0010 affected206 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0011 affected206 at risk
Migraine	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Partial seizures with secondary generalisation	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Presyncope	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Sciatica	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Spinal cord compression	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Syncope	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Wernicke's encephalopathy	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Device occlusion	Product Issues	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0010 affected206 at risk
Renal failure	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Renal impairment	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Urinary retention	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Balanoposthitis	Reproductive system and breast disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0013 affected206 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected411 at risk EG0010 affected206 at risk
Laryngeal dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0008 affected411 at risk EG0018 affected206 at risk
Laryngeal stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected411 at risk EG0010 affected206 at risk
Pneumothorax spontaneous	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Pulmonary alveolar haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Respiratory arrest	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Respiratory tract oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Tracheal stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Dermatitis exfoliative	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0010 affected206 at risk
Hypotension	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected411 at risk EG0011 affected206 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG0001 affected411 at risk EG0011 affected206 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.0	Systematic Assessment	EG00023 affected411 at risk EG0017 affected206 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00021 affected411 at risk EG0016 affected206 at risk
Cheilitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00022 affected411 at risk EG0011 affected206 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00033 affected411 at risk EG00120 affected206 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG000335 affected411 at risk EG00141 affected206 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00055 affected411 at risk EG00125 affected206 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00042 affected411 at risk EG00110 affected206 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00048 affected411 at risk EG00121 affected206 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00023 affected411 at risk EG0012 affected206 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00043 affected411 at risk EG00124 affected206 at risk
Oral pain	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00023 affected411 at risk EG0016 affected206 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG000107 affected411 at risk EG00112 affected206 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.0	Systematic Assessment	EG00040 affected411 at risk EG00120 affected206 at risk
Asthenia	General disorders	MedDRA 19.0	Systematic Assessment	EG00043 affected411 at risk EG00123 affected206 at risk
Fatigue	General disorders	MedDRA 19.0	Systematic Assessment	EG00061 affected411 at risk EG00121 affected206 at risk
Mucosal inflammation	General disorders	MedDRA 19.0	Systematic Assessment	EG000126 affected411 at risk EG00117 affected206 at risk
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG00029 affected411 at risk EG0017 affected206 at risk
Conjunctivitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG00021 affected411 at risk EG0012 affected206 at risk
Nasopharyngitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG00022 affected411 at risk EG00118 affected206 at risk
Paronychia	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG00085 affected411 at risk EG0014 affected206 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG00019 affected411 at risk EG00115 affected206 at risk
Weight decreased	Investigations	MedDRA 19.0	Systematic Assessment	EG00067 affected411 at risk EG00119 affected206 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.0	Systematic Assessment	EG00074 affected411 at risk EG00123 affected206 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG00013 affected411 at risk EG00117 affected206 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG00026 affected411 at risk EG0019 affected206 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG00011 affected411 at risk EG00111 affected206 at risk
Dizziness	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG00011 affected411 at risk EG00113 affected206 at risk
Dysgeusia	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG00034 affected411 at risk EG00110 affected206 at risk
Headache	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG00018 affected411 at risk EG00112 affected206 at risk
Anxiety	Psychiatric disorders	MedDRA 19.0	Systematic Assessment	EG00010 affected411 at risk EG00112 affected206 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG00035 affected411 at risk EG00130 affected206 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG00022 affected411 at risk EG00117 affected206 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG00054 affected411 at risk EG0013 affected206 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG00027 affected411 at risk EG00114 affected206 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG00022 affected411 at risk EG0012 affected206 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG000112 affected411 at risk EG0016 affected206 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG00076 affected411 at risk EG00116 affected206 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG00028 affected411 at risk EG0015 affected206 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG00030 affected411 at risk EG0010 affected206 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG00058 affected411 at risk EG00113 affected206 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG000188 affected411 at risk EG00134 affected206 at risk
Skin fissures	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG00040 affected411 at risk EG0011 affected206 at risk
Hypertension	Vascular disorders	MedDRA 19.0	Systematic Assessment	EG00018 affected411 at risk EG00112 affected206 at risk

Certain Agreements

ID	Term
D000577	Amides
D009930	Organic Chemicals
D011799	Quinazolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds