Trial With Cetuximab in Maintenance Therapy After Platinu... | NCT00820755

Description Module

Brief Summary

This open-label, randomized, multinational, non-comparative, phase IIIb trial with 2 parallel groups will screen about 1400 subjects with stage IIIB non-small cell lung cancer (NSCLC) with pleural effusion or stage IV NSCLC. It is expected that of approximately 1200 (85 percent) subjects who will be included, about 1000 will be Caucasian; about 120 Asian, and the remainder (about 80) will be of other ethnic origin (that is neither Caucasian nor Asian). Approximately 480 (40 percent) subjects are expected to be free of progression at the end of combination treatment with cetuximab and platinum-based chemotherapy. These subjects will be eligible for randomization to intravenous cetuximab maintenance therapy with either 500 milligram per square meter (mg/m^2) every 2 weeks or 250 mg/m^2 weekly (q1w); about 240 subjects are expected per group.

The trial will be performed in a community practice setting, with approximately 230 centers participating in the trial worldwide (planned countries are Argentina, Australia, Austria, Belgium, Brazil, Chile, China, Colombia, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Mexico, Netherlands, Poland, Portugal, Russia, Singapore, Slovakia, South Africa, South Korea, Spain, Switzerland, Taiwan, Turkey, United Kingdom and Venezuela). With noncompetitive enrollment, approximately 4 to 8 subjects are expected to be enrolled at each center. Enrollment in the individual centers is generally limited to a maximum of 8 subjects. If any of these subjects does not receive trial treatment for any reason or discontinue all trial treatment at the first visit, additional subjects may be enrolled until 8 subjects were treated. The primary endpoint of the trial will be overall survival time from inclusion into the trial to death. Additional secondary efficacy endpoints will be time to treatment failure, tumor response, and disease control rate. Other endpoints will include safety and toxicity, compliance with maintenance therapy, subject satisfaction and translational research (TR) (for subjects with tumor samples available).

Label	Type	Intervention Names
Cetuximab 250 mg/m^2 q1w + Platinum-based Doublet Chemotherapy	Active Comparator	Drug: Cetuximab plus Platinum-based Doublet Chemotherapy
Cetuximab 500 mg/m^2 every 2 weeks	Active Comparator	Drug: Cetuximab 500 mg/m^2
Cetuximab 250 mg/m^2 weekly	Active Comparator	Drug: Cetuximab 250 mg/m^2

Name	Type	Description	Arm Group Labels	Other Names
Cetuximab plus Platinum-based Doublet Chemotherapy	Drug	Single first dose of cetuximab 400 mg/m^2 infusion will be administered intravenously over 120 minutes (min) followed by cetuximab 250 mg/m^2 intravenous infusion over 60 min q1w with background platinum-based doublet chemotherapy up to maximum of 6 cycles, until progressive disease, unacceptable toxicity, or withdrawal of consent. Platinum based doublet chemotherapy will be administered as intravenous infusion as per study center included: vinorelbine 25 mg/m^2 on Day 1 (D1) and Day 8 (D8)+cisplatin 80 mg/m^2 on D1; or gemcitabine 1250 mg/m^2 on D1 and D8+cisplatin 75 mg/m^2 on D1; or gemcitabine 1000 mg/m^2 on D1 and D8+carboplatin at dose to reach area under curve (AUC)5 milligramhour/milliliter (mghr/mL) on D1; or Docetaxel 75 mg/m^2 on D1+cisplatin 75 mg/m^2 on D1; or paclitaxel 175 mg/m^2 on D1+cisplatin 80 mg/m^2 on D1; or paclitaxel 200 mg/m^2 on D1+carboplatin at dose to reach AUC6 mg*hr/mL on D1, of each 3-week treatment cycle for a maximum of 6 cycles.

Measure	Description	Time Frame
Overall Survival (OS) Time	The OS time is defined as the time from trial inclusion to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier.	Time from trial inclusion to death or last day known to be alive, reported between day of first participant included, that is, Jan 2009 until cut-off date (17 Dec 2011)
Percentage of Participants With 1-year Overall Survival	The OS time is defined as the time from trial inclusion to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier. Percentage of participants who were still alive until one year after the last participant was included (March 2010).	Time from trial inclusion to death or last day known to be alive, reported between day of first participant included, that is, Jan 2009 until one year after the last participant was included (March 2010)

Measure	Description	Time Frame
Overall Survival (OS) Time (From Randomization to Cetuximab Maintenance Regimen Until Death)	The OS time is defined as the time from randomization in cetuximab maintenance regimen to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier.	Time from randomization in cetuximab maintenance regimen to death or last day known to be alive, reported between day of first participant randomized, that is, May 2009 until cut-off date (17 Dec 2011)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject has given written informed consent before any trial-related activities are carried out
Male or female, greater than or equal to (>=)18 years of age at the time of informed consent, inpatient or outpatient
Diagnosis of histologically or cytologically confirmed NSCLC, stage IIIB NSCLC with pleural effusion or stage IV
Presence of at least 1 uni-dimensionally measurable index lesion, whereby index lesions must not lie in a previously irradiated area
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at inclusion in the trial
White blood count>= 3 * 10^9 per liter (/L) with neutrophils >= 1.5 * 10^9 /L , platelet count >=100 * 10^9 /L , and hemoglobin >= 5.6 millimole per liter (mmol/L) (9 gram per deciliter [g/dL])
Total bilirubin less than or equal to (=<)1.5 * upper limit of normal (ULN) range
Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) =< 5 * ULN
Glomerular filtration rate (GFR) >=60 milliliter per minute (mL/min). The creatinine clearance (CrCl) estimated based on the Cockroft-Gault formula is used as a surrogate for the GFR
Effective contraception that is, barrier method (condoms, diaphragm), oral, injectable or implant birth control, for both male and female subjects during the whole trial period and for at least 6 months after the end of trial treatment, if the risk of conception exists
Recovered from relevant toxicities prior to inclusion in the trial

Exclusion Criteria:

Previous exposure to Epidermal Growth Factor Receptor (EGFR)-targeting therapy
Previous chemotherapy for NSCLC; neo-adjuvant or adjuvant (radio-)chemotherapy is allowed if it was finished 6 months prior to start of trial treatment
Major surgery within 30 days prior to inclusion in the trial
Prior chest irradiation within 90 days prior to inclusion in the trial (palliative radiation of bone lesions is allowed)
Participation in another clinical trial or treatment with any investigational agent(s) within 30 days prior to inclusion in the trial
Concurrent chronic systemic immune therapy, chemotherapy for disease other than cancer, or hormone therapy for the treatment of cancer not indicated in the trial protocol
Documented or symptomatic brain metastasis
Pre-existing ascites Grade >= 2 and/or pericardial effusion Grade >= 2
Superior vena cava syndrome contra-indicating hydration
Previous malignancy in the last 5 years except basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix
Active infection (infection requiring intravenous antibiotics), including active tuberculosis, known and declared human immunodeficiency virus (HIV)
Myocardial infarction within 6 months prior to inclusion into the trial, uncontrolled congestive heart failure; or any current Grade 3 or 4 cardio-vascular disorder despite treatment
Known hypersensitivity reaction to any of the components of trial treatments
Symptomatic peripheral neuropathy National Cancer Institute-Common Toxicity Criteria (NCI-CTC) Grade >= 2 and/or ototoxicity Grade >= 2, except if due to trauma or mechanical impairment due to tumor mass
History of significant neurologic or psychiatric disorders including dementia, seizures, bipolar disorder
Medical or psychological condition that would not permit the subject to complete the trial or sign informed consent
Legal incapacity or limited legal capacity
Known drug abuse
Pregnancy (absence to be confirmed by serum beta-human chorionic gonadotropin [beta-HCG test]) or lactation period

Name	Affiliation	Role
Steffen Heeger, MD MSc	Merck KGaA, Darmstadt, Germany	Study Director

PubMed Identifier	Type	Citation	Retractions
25195590	Derived	Heigener DF, Pereira JR, Felip E, Mazal J, Manzyuk L, Tan EH, Merimsky O, Sarholz B, Esser R, Gatzemeier U. Weekly and every 2 weeks cetuximab maintenance therapy after platinum-based chemotherapy plus cetuximab as first-line treatment for non-small cell lung cancer: randomized non-comparative phase IIIb NEXT trial. Target Oncol. 2015 Jun;10(2):255-65. doi: 10.1007/s11523-014-0336-7. Epub 2014 Sep 9.

ID	Title	Description
FG000	Cetuximab 250 mg/m^2 q1w + Platinum-based Doublet Chemotherapy	Combination Phase: Single first dose of cetuximab 400 milligram per square meter (mg/m^2) infusion administered intravenously over 120 minutes (min) followed by cetuximab 250 mg/m^2 intravenous infusion over 60 min weekly (q1w) with background platinum-based doublet chemotherapy up to maximum of 6 cycles, until progressive disease, unacceptable toxicity, or withdrawal of consent. Platinum based doublet chemotherapy infusion intravenously as per study center included: vinorelbine 25 mg/m^2 on Day 1 (D1) and Day 8 (D8)+cisplatin 80 mg/m^2 on D1; or gemcitabine 1250 mg/m^2 on D1 and D8+cisplatin 75 mg/m^2 on D1; or gemcitabine 1000 mg/m^2 on D1 and D8+carboplatin at dose to reach area under curve (AUC)5 mghour/milliliter (mgh/mL) on D1; or Docetaxel 75 mg/m^2 on D1+cisplatin 75 mg/m^2 on D1; or paclitaxel 175 mg/m^2 on D1+cisplatin 80 mg/m^2 on D1; or paclitaxel 200 mg/m^2 on D1+carboplatin at dose to reach AUC6 mg*h/mL on D1, of each 3-week treatment cycle for a maximum of 6 cycles.

ID	Title	Description
BG000	Cetuximab 250 mg/m^2 q1w + Platinum-based Doublet Chemotherapy	Combination Phase: Single first dose of cetuximab 400 milligram per square meter (mg/m^2) infusion administered intravenously over 120 minutes (min) followed by cetuximab 250 mg/m^2 intravenous infusion over 60 min weekly (q1w) with background platinum-based doublet chemotherapy up to maximum of 6 cycles, until progressive disease, unacceptable toxicity, or withdrawal of consent. Platinum based doublet chemotherapy infusion intravenously as per study center included: vinorelbine 25 mg/m^2 on Day 1 (D1) and Day 8 (D8)+cisplatin 80 mg/m^2 on D1; or gemcitabine 1250 mg/m^2 on D1 and D8+cisplatin 75 mg/m^2 on D1; or gemcitabine 1000 mg/m^2 on D1 and D8+carboplatin at dose to reach area under curve (AUC)5 mghour/milliliter (mgh/mL) on D1; or Docetaxel 75 mg/m^2 on D1+cisplatin 75 mg/m^2 on D1; or paclitaxel 175 mg/m^2 on D1+cisplatin 80 mg/m^2 on D1; or paclitaxel 200 mg/m^2 on D1+carboplatin at dose to reach AUC6 mg*h/mL on D1, of each 3-week treatment cycle for a maximum of 6 cycles.

Units	Counts
Participants	BG000583

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) Time

The OS time is defined as the time from trial inclusion to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier.

Intention-to-treat (ITT) maintenance analysis set included all participants who were included in ITT (all the participants enrolled in this study) analysis set, judged to be progression-free (based on computer tomography [CT] or magnetic resonance imaging [MRI] scan) by the Investigator and randomized to maintenance therapy.

Posted

Median

95% Confidence Interval

months

Time from trial inclusion to death or last day known to be alive, reported between day of first participant included, that is, Jan 2009 until cut-off date (17 Dec 2011)

ID	Title	Description
OG000	Cetuximab 500 mg/m^2 Every 2 Weeks	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 500 mg/m^2 as intravenous infusion every 2 weeks, until progressive disease (PD), unacceptable toxicity, or withdrawal of consent.
OG001	Cetuximab 250 mg/m^2 Weekly	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 250 mg/m^2 as intravenous infusion weekly, until PD, unacceptable toxicity, or withdrawal of consent.

Units	Counts
Participants	OG000157 OG001154

Title

Denominators

Categories

Title	Measurements
	OG00016.1(13.6 to 18.2) OG00115.5(13.2 to 19.7)

Secondary

Overall Survival (OS) Time (From Randomization to Cetuximab Maintenance Regimen Until Death)

The OS time is defined as the time from randomization in cetuximab maintenance regimen to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier.

ITT maintenance analysis set included all participants who were included in ITT (all the participants enrolled in this study) analysis set, judged to be progression-free (based on CT or MRI scan) by the Investigator and randomized to maintenance therapy.

Posted

Median

95% Confidence Interval

months

Time from randomization in cetuximab maintenance regimen to death or last day known to be alive, reported between day of first participant randomized, that is, May 2009 until cut-off date (17 Dec 2011)

ID	Title	Description
OG000	Cetuximab 500 mg/m^2 Every 2 Weeks	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 500 mg/m^2 as intravenous infusion every 2 weeks, until progressive disease (PD), unacceptable toxicity, or withdrawal of consent.
OG001	Cetuximab 250 mg/m^2 Weekly	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 250 mg/m^2 as intravenous infusion weekly, until PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Time to Treatment Failure

Time to treatment failure is defined as the time from trial inclusion to date of either first occurrence of progression, discontinuation of treatment due to progression or adverse event, withdrawal of consent or lost to follow up, start of further anticancer therapy, or death, whichever is earlier. Participants without events are censored either at the time of their last drug intake, or on the day of inclusion (Day 1) if they received no study drug.

Posted

Median

95% Confidence Interval

months

Time from trial inclusion to treatment failure or last drug intake, reported between day of first participant included, that is, Jan 2009 until cut-off date (17 Dec 2011)

ID	Title	Description
OG000	Cetuximab 500 mg/m^2 Every 2 Weeks	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 500 mg/m^2 as intravenous infusion every 2 weeks, until progressive disease (PD), unacceptable toxicity, or withdrawal of consent.
OG001	Cetuximab 250 mg/m^2 Weekly	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 250 mg/m^2 as intravenous infusion weekly, until PD, unacceptable toxicity, or withdrawal of consent.

Secondary

Time to Treatment Failure (From Randomization to Cetuximab Maintenance Regimen Until Death)

Time from randomization in cetuximab maintenance regimen to date of either first occurrence of progression, discontinuation of treatment due to progression or adverse event, withdrawal of consent or lost to follow up, start of further anticancer therapy, or death, whichever is earlier. Participants without events are censored either at the time of their last drug intake, or on the day of randomization (Day 1 of maintenance therapy) if they received no study drug.

Posted

Median

95% Confidence Interval

months

Time from randomization in cetuximab maintenance regimen to treatment failure or last drug intake, reported between day of first participant randomized, that is, May 2009 until cut-off date (17 Dec 2011)

ID	Title	Description
OG000	Cetuximab 500 mg/m^2 Every 2 Weeks	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 500 mg/m^2 as intravenous infusion every 2 weeks, until progressive disease (PD), unacceptable toxicity, or withdrawal of consent.
OG001	Cetuximab 250 mg/m^2 Weekly

Secondary

Percentage of Participants With Best Unconfirmed Tumor Response in the Combination Therapy Phase

The response rate is defined as the percentage of participants having achieved complete response (CR) or partial response (PR) as the unconfirmed best overall response (BOR) according to centrally reviewed investigator assessments based on an independent review charter (IRC). As per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: CR = Disappearance of all target lesions; PR = at least 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

ITT analysis set included all participants enrolled in this study.

Posted

Number

95% Confidence Interval

percentage of participants

Evaluations were performed every 2 cycles during combination therapy period until progression and at the end of combination therapy period, reported between day of first participant included, that is, Jan 2009, until cut-off date, (17 Dec 2011)

ID	Title	Description
OG000	Cetuximab 250 mg/m^2 q1w + Platinum-based Doublet Chemotherapy	Combination Phase: Single first dose of cetuximab 400 milligram per square meter (mg/m^2) infusion administered intravenously over 120 minutes (min) followed by cetuximab 250 mg/m^2 intravenous infusion over 60 min weekly (q1w) with background platinum-based doublet chemotherapy up to maximum of 6 cycles, until progressive disease, unacceptable toxicity, or withdrawal of consent. Platinum based doublet chemotherapy infusion intravenously as per study center included: vinorelbine 25 mg/m^2 on Day 1 (D1) and Day 8 (D8)+cisplatin 80 mg/m^2 on D1; or gemcitabine 1250 mg/m^2 on D1 and D8+cisplatin 75 mg/m^2 on D1; or gemcitabine 1000 mg/m^2 on D1 and D8+carboplatin at dose to reach area under curve (AUC)5 mghour/milliliter (mgh/mL) on D1; or Docetaxel 75 mg/m^2 on D1+cisplatin 75 mg/m^2 on D1; or paclitaxel 175 mg/m^2 on D1+cisplatin 80 mg/m^2 on D1; or paclitaxel 200 mg/m^2 on D1+carboplatin at dose to reach AUC6 mg*h/mL on D1, of each 3-week treatment cycle for a maximum of 6 cycles.

Secondary

Percentage of Participant With Best Unconfirmed Tumor Response for the Whole Study Period

The response rate is defined as the percentage of participants having achieved CR and PR as the BOR according to IRC assessment in combination therapy phase and radiological assessments (based on response evaluation criteria in solid tumors [RECIST] Version 1.0) in the maintenance therapy phase. As per RECIST v1.0 for target lesions and assessed by MRI: CR = Disappearance of all target lesions; PR = at least 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Posted

Number

95% Confidence Interval

percentage of participants

Evaluations were performed every 2 cycles during combination therapy and 6-weekly during maintenance therapy period until progression and at end of both periods, reported between day of first participant included, Jan 2009 until cut-off date (17 Dec 2011)

ID	Title	Description
OG000	Cetuximab 500 mg/m^2 Every 2 Weeks	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 500 mg/m^2 as intravenous infusion every 2 weeks, until progressive disease (PD), unacceptable toxicity, or withdrawal of consent.
OG001

Secondary

Percentage of Participants With Disease Control in the Combination Therapy Phase

The disease control rate is defined as the percentage of participants having achieved complete response or partial response or stable disease as the unconfirmed BOR according to IRC assessment.

ITT analysis set included all participants enrolled in this study.

Posted

Number

95% Confidence Interval

percentage of participants

ID	Title	Description
OG000	Cetuximab 250 mg/m^2 q1w + Platinum-based Doublet Chemotherapy	Combination Phase: Single first dose of cetuximab 400 milligram per square meter (mg/m^2) infusion administered intravenously over 120 minutes (min) followed by cetuximab 250 mg/m^2 intravenous infusion over 60 min weekly (q1w) with background platinum-based doublet chemotherapy up to maximum of 6 cycles, until progressive disease, unacceptable toxicity, or withdrawal of consent. Platinum based doublet chemotherapy infusion intravenously as per study center included: vinorelbine 25 mg/m^2 on Day 1 (D1) and Day 8 (D8)+cisplatin 80 mg/m^2 on D1; or gemcitabine 1250 mg/m^2 on D1 and D8+cisplatin 75 mg/m^2 on D1; or gemcitabine 1000 mg/m^2 on D1 and D8+carboplatin at dose to reach area under curve (AUC)5 mghour/milliliter (mgh/mL) on D1; or Docetaxel 75 mg/m^2 on D1+cisplatin 75 mg/m^2 on D1; or paclitaxel 175 mg/m^2 on D1+cisplatin 80 mg/m^2 on D1; or paclitaxel 200 mg/m^2 on D1+carboplatin at dose to reach AUC6 mg*h/mL on D1, of each 3-week treatment cycle for a maximum of 6 cycles.

Secondary

Percentage of Participants With Disease Control for the Whole Study Period

The disease control rate is defined as the percentage of participants having achieved complete response or partial response or stable disease as the unconfirmed best overall response according to IRC assessment in combination therapy phase and radiological assessments (based on RECIST Version 1.0 criteria) in the maintenance therapy phase.

Posted

Number

95% Confidence Interval

percentage of participants

ID	Title	Description
OG000	Cetuximab 500 mg/m^2 Every 2 Weeks	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 500 mg/m^2 as intravenous infusion every 2 weeks, until progressive disease (PD), unacceptable toxicity, or withdrawal of consent.
OG001	Cetuximab 250 mg/m^2 Weekly	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 250 mg/m^2 as intravenous infusion weekly, until PD, unacceptable toxicity, or withdrawal of consent.

Primary

Percentage of Participants With 1-year Overall Survival

The OS time is defined as the time from trial inclusion to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whichever is earlier. Percentage of participants who were still alive until one year after the last participant was included (March 2010).

Posted

Number

95% Confidence Interval

percentage of participants

Time from trial inclusion to death or last day known to be alive, reported between day of first participant included, that is, Jan 2009 until one year after the last participant was included (March 2010)

ID	Title	Description
OG000	Cetuximab 500 mg/m^2 Every 2 Weeks	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 500 mg/m^2 as intravenous infusion every 2 weeks, until progressive disease (PD), unacceptable toxicity, or withdrawal of consent.
OG001	Cetuximab 250 mg/m^2 Weekly	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 250 mg/m^2 as intravenous infusion weekly, until PD, unacceptable toxicity, or withdrawal of consent.

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cetuximab 250 mg/m^2 q1w + Platinum-based Doublet Chemotherapy	Combination Phase: Single first dose of cetuximab 400 milligram per square meter (mg/m^2) infusion administered intravenously over 120 minutes (min) followed by cetuximab 250 mg/m^2 intravenous infusion over 60 min weekly (q1w) with background platinum-based doublet chemotherapy up to maximum of 6 cycles, until progressive disease, unacceptable toxicity, or withdrawal of consent. Platinum based doublet chemotherapy infusion intravenously as per study center included: vinorelbine 25 mg/m^2 on Day 1 (D1) and Day 8 (D8)+cisplatin 80 mg/m^2 on D1; or gemcitabine 1250 mg/m^2 on D1 and D8+cisplatin 75 mg/m^2 on D1; or gemcitabine 1000 mg/m^2 on D1 and D8+carboplatin at dose to reach area under curve (AUC)5 mghour/milliliter (mgh/mL) on D1; or Docetaxel 75 mg/m^2 on D1+cisplatin 75 mg/m^2 on D1; or paclitaxel 175 mg/m^2 on D1+cisplatin 80 mg/m^2 on D1; or paclitaxel 200 mg/m^2 on D1+carboplatin at dose to reach AUC6 mg*h/mL on D1, of each 3-week treatment cycle for a maximum of 6 cycles.	243	583	564	583
EG001	Cetuximab 500 mg/m^2 Every 2 Weeks	Participants who were free of disease progression after combination therapy, they administered with cetuximab 500 mg/m^2 intravenously for 2 weeks, for up to PD, development of unacceptable toxicities, or withdrawal of consent after the end of combination therapy.	30	156	121	156
EG002	Cetuximab 250 mg/m^2 Weekly	Participants who were free of disease progression at the end of combination therapy, entered in the maintenance therapy period. In the maintenance period, participants received cetuximab 250 mg/m^2 as intravenous infusion weekly, until PD, unacceptable toxicity, or withdrawal of consent.	33	155	136	155

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0006 affected583 at risk EG0011 affected156 at risk EG0021 affected155 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG00013 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0008 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00011 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0009 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0022 affected155 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Asthenia	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0008 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Fatigue	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0006 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Pyrexia	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0009 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Non-cardiac chest pain	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Oedema peripheral	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0012 affected156 at risk EG0021 affected155 at risk
Platelet count decreased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG0005 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Alanine aminotransferase increased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
White blood cell count decreased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Neutrophil count decreased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG0003 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0004 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0005 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Dizziness	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Headache	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00010 affected583 at risk EG0012 affected156 at risk EG0022 affected155 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0003 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Bone marrow failure	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Febdrile bone marrow aplasia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG00020 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Granulocytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG00032 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG0004 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Angina unstable	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Arrhythmia superaventricular	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0003 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Cardiac arrest	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Cardiac failure	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Cardiovascular insufficiency	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Electromechanical dissociation	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Myocardial infarction	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Pericardial effusion	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0011 affected156 at risk EG0021 affected155 at risk
Pericarditis	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Right ventricular dysfunction	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Tachycardia	Cardiac disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Aplasia	Congenital, familial and genetic disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Reflux oesophagitis	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Death	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0003 affected583 at risk EG0012 affected156 at risk EG0020 affected155 at risk
Device leakage	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Disease progression	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0012 affected156 at risk EG0021 affected155 at risk
General physical health deterioration	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0004 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Infusion related reaction	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Multi-organ failure	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Organ failure	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pain	General disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 14.0	Non-systematic Assessment	EG0003 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Anaphylactic shock	Immune system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 14.0	Non-systematic Assessment	EG0008 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Anorectal infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Bronchitis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Cellulitis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Device related infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Empyema	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Febrile infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Herpes zoster	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Kidney infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0005 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Lower respiratory tract infection bacterial	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Lung infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Neutropenic sepsis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pneumonia	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG00017 affected583 at risk EG0014 affected156 at risk EG0024 affected155 at risk
Pseudomembranous colitis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pyothorax	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Respiratory tract infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Sepsis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0003 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Septic shock	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Skin infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0012 affected156 at risk EG0020 affected155 at risk
Anastomotic ulcer	Injury, poisoning and procedural complications	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Blood creatinine increased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
C-Reactive protein increased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0004 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Malignant pleural effusion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pericardial effusion malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0003 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0003 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Cognitive disorder	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Convulsion	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0011 affected156 at risk EG0021 affected155 at risk
Dementia Alzheimer's type	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pyramidal tract syndrome	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Spinal cord compression	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Syncope	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Disorientation	Psychiatric disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Haematuria	Renal and urinary disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Renal failure	Renal and urinary disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Bronchostenosis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0006 affected583 at risk EG0012 affected156 at risk EG0022 affected155 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0005 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00012 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Respiratory acidosis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pruritus generalised	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Aortic thrombosis	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0003 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Femoral artery embolism	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hypotension	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0003 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Thrombophlebitis	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Diplopia	Eye disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Melaena	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Mesenteric artery thrombosis	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Bronchopneumonia	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Endocarditis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Neutropenic infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Pulmonary tuberculosis	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Operative haemorrhage	Injury, poisoning and procedural complications	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Renal injury	Injury, poisoning and procedural complications	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Fasciitis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Altered state of consciousness	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Mental impairment	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Hydropneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0011 affected156 at risk EG0020 affected155 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Arterial thrombosis	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Circulatory collapse	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Hypersensitivity	Immune system disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0004 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0005 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0001 affected583 at risk EG0010 affected156 at risk EG0021 affected155 at risk
Hypertension	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG0002 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG000134 affected583 at risk EG0019 affected156 at risk EG00215 affected155 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG00072 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG000208 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Non-systematic Assessment	EG000112 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 14.0	Non-systematic Assessment	EG00013 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00021 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00031 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG000109 affected583 at risk EG0013 affected156 at risk EG00212 affected155 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG000120 affected583 at risk EG0016 affected156 at risk EG00215 affected155 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00036 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG000212 affected583 at risk EG0013 affected156 at risk EG0029 affected155 at risk
Odynophagia	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG0005 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00047 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Non-systematic Assessment	EG000122 affected583 at risk EG0012 affected156 at risk EG0028 affected155 at risk
Asthenia	General disorders	MedDRA 14.0	Non-systematic Assessment	EG000124 affected583 at risk EG0016 affected156 at risk EG00216 affected155 at risk
Chills	General disorders	MedDRA 14.0	Non-systematic Assessment	EG00016 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Fatigue	General disorders	MedDRA 14.0	Non-systematic Assessment	EG000114 affected583 at risk EG0017 affected156 at risk EG00213 affected155 at risk
Influenza like illness	General disorders	MedDRA 14.0	Non-systematic Assessment	EG00011 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Mucosal Inflammation	General disorders	MedDRA 14.0	Non-systematic Assessment	EG00067 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Non-cardiac chest pain	General disorders	MedDRA 14.0	Non-systematic Assessment	EG00023 affected583 at risk EG0018 affected156 at risk EG0027 affected155 at risk
Oedema peripheral	General disorders	MedDRA 14.0	Non-systematic Assessment	EG00021 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pyrexia	General disorders	MedDRA 14.0	Non-systematic Assessment	EG00069 affected583 at risk EG0019 affected156 at risk EG00210 affected155 at risk
Paronychia	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG00030 affected583 at risk EG0019 affected156 at risk EG00212 affected155 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.0	Non-systematic Assessment	EG00024 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Alanine aminotransferase increased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG00026 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Haemoglobin decreased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG00040 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Neutrophil count decreased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG00019 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Platelet count decreased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG00040 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
White blood cell count decreased	Investigations	MedDRA 14.0	Non-systematic Assessment	EG00020 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG000112 affected583 at risk EG0018 affected156 at risk EG00213 affected155 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG00037 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG00069 affected583 at risk EG0019 affected156 at risk EG00214 affected155 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 14.0	Non-systematic Assessment	EG00014 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00033 affected583 at risk EG0015 affected156 at risk EG00211 affected155 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00030 affected583 at risk EG0016 affected156 at risk EG0028 affected155 at risk
Hypercreatinaemia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0005 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00026 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00031 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Dizziness	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG00035 affected583 at risk EG0014 affected156 at risk EG0028 affected155 at risk
Dysgeusia	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG00028 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Headache	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG00029 affected583 at risk EG0017 affected156 at risk EG0029 affected155 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG00026 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Peripheral motor neuropathy	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG0008 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 14.0	Non-systematic Assessment	EG00038 affected583 at risk EG0019 affected156 at risk EG0026 affected155 at risk
Insomnia	Psychiatric disorders	MedDRA 14.0	Non-systematic Assessment	EG00031 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00069 affected583 at risk EG00114 affected156 at risk EG00214 affected155 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00049 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00043 affected583 at risk EG00120 affected156 at risk EG00222 affected155 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00017 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00015 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Non-systematic Assessment	EG00013 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG000306 affected583 at risk EG00140 affected156 at risk EG00240 affected155 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG000109 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00083 affected583 at risk EG00111 affected156 at risk EG00216 affected155 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00051 affected583 at risk EG00110 affected156 at risk EG0026 affected155 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00046 affected583 at risk EG0019 affected156 at risk EG00211 affected155 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG00031 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0006 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Hypertension	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG00019 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Phlebitis	Vascular disorders	MedDRA 14.0	Non-systematic Assessment	EG00013 affected583 at risk EG0010 affected156 at risk EG0020 affected155 at risk
Conjunctivitis	Eye disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0017 affected156 at risk EG00210 affected155 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG00110 affected156 at risk EG0026 affected155 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG0012 affected156 at risk EG0028 affected155 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 14.0	Non-systematic Assessment	EG0000 affected583 at risk EG00111 affected156 at risk EG00213 affected155 at risk

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins