A Study for Non-Smoker Patients With Nonsquamous Non-Smal... | NCT00550173

ID	Type	Description	Link
H3E-MC-S103	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
Pemetrexed + Erlotinib	Experimental	Pemetrexed 500 milligrams per meter squared (mg/m^2) of body surface area, administered by intravenous (IV) infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Drug: pemetrexed Drug: erlotinib
Erlotinib	Active Comparator	Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.	Drug: erlotinib
Pemetrexed	Active Comparator	Pemetrexed 500 mg/m^2 of body surface area, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.	Drug: pemetrexed

Name	Type	Description	Arm Group Labels	Other Names
pemetrexed	Drug	500 milligrams per meter squared (mg/m^2), intravenous (IV), every (q) 21 days until progression or unacceptable toxicity develops	Pemetrexed Pemetrexed + Erlotinib

Measure	Description	Time Frame
Progression-Free Survival (PFS)	PFS is defined as the time from randomization to the first date of progressive disease (PD; either objectively determined or clinical progression) or death from any cause. PD was defined as at least a 20% increase in sum of longest diameter of target lesions as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines. Time to disease progression was censored at the date of death.	Randomization to measured PD up to 38 months

Measure	Description	Time Frame
Percentage of Participants With a Tumor Response of Complete Response (CR) or Partial Response (PR) [Tumor Response Rate (TRR)]	TRR was defined as the number of responders (complete or partial) divided by the number of participants qualified for tumor response, as assessed using the RECIST version 1.0 guideline, multiplied by 100. RECIST guidelines: CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; PR was defined as at least a 30% decrease in sum of longest diameter of target lesions.

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.		Barretos		14784700

PubMed Identifier	Type	Citation	Retractions
23890768	Derived	Lee DH, Lee JS, Kim SW, Rodrigues-Pereira J, Han B, Song XQ, Wang J, Kim HK, Sahoo TP, Digumarti R, Wang X, Altug S, Orlando M. Three-arm randomised controlled phase 2 study comparing pemetrexed and erlotinib to either pemetrexed or erlotinib alone as second-line treatment for never-smokers with non-squamous non-small cell lung cancer. Eur J Cancer. 2013 Oct;49(15):3111-21. doi: 10.1016/j.ejca.2013.06.035. Epub 2013 Jul 24.

ID	Title	Description
FG000	Pemetrexed + Erlotinib	Pemetrexed 500 milligrams per meter squared (mg/m^2) of body surface area, administered by intravenous (IV) infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
FG001

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

Progression-Free Survival (PFS)

PFS is defined as the time from randomization to the first date of progressive disease (PD; either objectively determined or clinical progression) or death from any cause. PD was defined as at least a 20% increase in sum of longest diameter of target lesions as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines. Time to disease progression was censored at the date of death.

Qualified Intent to Treat (Q-ITT) Population defined as all participants with nonsquamous histology, who were randomized to therapy.

Posted

Median

95% Confidence Interval

months

Randomization to measured PD up to 38 months

ID	Title	Description
OG000	Pemetrexed + Erlotinib	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG001	Erlotinib	Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG002	Pemetrexed	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.

Units	Counts
Participants	OG00078 OG00182 OG00280

Title

Denominators

Categories

Title	Measurements
	OG0007.4(4.4 to 12.9) OG0013.8(2.7 to 6.3) OG0024.4(3.0 to 6.0)

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 OG002	Overall; Global null hypothesis was rejected at 2-sided 0.2 significance level.	Regression, Cox	Model is adjusted to covariates ECOG PS (0/1 vs.2), histological subtype (adeno vs. non-adeno), race (East Asian and non-East Asian) and gender.	0.003	If global test across 3 arms is significant at a 2-sided 0.2 level, then conduct 2-sided pairwise tests between combination and each single agent under the global model. Significance is claimed only if both the global and pairwise tests p<0.05.												No	Superiority or Other

Secondary

Percentage of Participants With a Tumor Response of Complete Response (CR) or Partial Response (PR) [Tumor Response Rate (TRR)]

TRR was defined as the number of responders (complete or partial) divided by the number of participants qualified for tumor response, as assessed using the RECIST version 1.0 guideline, multiplied by 100. RECIST guidelines: CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; PR was defined as at least a 30% decrease in sum of longest diameter of target lesions.

Q-ITT Population - Tumor Analyzable (Q-ITT-TA) Population: defined as all participants with nonsquamous histology, who were randomized to therapy and had measurable or evaluable lesions at baseline.

Posted

Number

percentage of participants

Randomization to measured disease progression up to 38 months

ID	Title	Description
OG000	Pemetrexed + Erlotinib	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG001	Erlotinib	Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.

Secondary

Overall Survival (OS)

OS is defined as the time from randomization to the date of death from any cause.

Q-ITT Population: defined as all participants with nonsquamous histology, who were randomized to therapy. Survival time was censored at the date of last contact for participants who were still alive or lost to follow-up, number of participants censored 35 (pemetrexed plus erlotinib), 44 (erlotinib) and 31 (pemetrexed).

Posted

Median

95% Confidence Interval

months

Baseline to date of death from any cause up to 45.5 months

ID	Title	Description
OG000	Pemetrexed + Erlotinib	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG001	Erlotinib	Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG002	Pemetrexed	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.

Secondary

Number of Participants With Adverse Events

A summary of serious and all other non-serious adverse events (AEs), which include AEs reported for pharmacological toxicity, is located in the Reported Adverse Event module.

Safety Population defined as non-squamous participants who received at least 1 dose of study therapy (pemetrexed plus erlotinib or pemetrexed or erlotinib). One participant was assigned to pemetrexed (single therapy) but received erlotinib (single therapy) at first cycle and this lead to the discrepancy of participants for the safety analysis.

Posted

Number

participants

Randomization up to 39 months

ID	Title	Description
OG000	Pemetrexed + Erlotinib	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG001	Erlotinib	Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG002	Pemetrexed	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.

Secondary

Percentage of Participants With CR, PR, and Stable Disease (SD) - Disease Control Rate (DCR)

DCR was defined as the percentage of participants with CR, PR, or SD divided by the number of randomized and treated participants as assessed using the RECIST criteria. CR was defined as the disappearance of all target lesions; PR was defined as 1) at least a 30% decrease in sum of longest diameter of target lesions or 2) complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions; PD was defined as at least a 20% increase in sum of longest diameter of target lesions; SD was defined as small changes that did not meet the above criteria.

Q-ITT-TA Population: defined as all participants, with nonsquamous histology, who were randomized to therapy and had measurable or evaluable lesions at baseline.

Posted

Number

percentage of participants

Randomization to disease progression up to 38 months

ID	Title	Description
OG000	Pemetrexed + Erlotinib	Pemetrexed 500 mg/m^2 of body surface area, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG001	Erlotinib	Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.

Secondary

Time to Worsening of Symptoms (TWS) on Lung Cancer Symptoms Scale (LCSS)

TWS assessed using the LCSS a participant rated lung cancer instrument which consisted of 9 disease related symptoms and quality of life (QoL) items, with 6 subscales related to major lung cancer symptoms (appetite, cough, fatigue, dyspnea, hemoptysis, and pain) and 3 summation items related to QoL (activity status, symptomatic distress, and overall QoL). Each item is marked on a visual analog scale (VAS) 0 (low symptoms/QoL items) to 100 (high symptoms/QoL items). The mean of the 6 subscales is used to calculate the average symptom burden index. TWS was measured from the date of study enrollment to the first date of a worsening in any 1 of the 6 LCSS symptom-specific items (as defined by a VAS 15-mm increase from baseline in the patient-reported score for any of these 6 items).

A subset of the Q-ITT Population that included participants with LCSS results; Q-ITT Population: defined as all participants, with nonsquamous histology, who were randomized to therapy.

Posted

Median

95% Confidence Interval

months

Randomization to first date of worsening of any of 6 LCSS symptom specific items or up to 12.4 months

ID	Title	Description
OG000	Pemetrexed + Erlotinib	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG001	Erlotinib

Secondary

Number of Participants With Mutated or Non-Mutated Epidermal Growth Factor Receptor (EGFR) Genotype Status

EGFR mutation status was defined as: participants with any mutations detected were categorized as mutated and participants without any mutations detected were categorized as non-mutated.

A subset of the Q-ITT Population who had EGFR samples; Q-ITT Population: defined as all participants with nonsquamous histology, who were randomized to therapy.

Posted

Number

participants

Randomization to date of PD or death up to 38 months

ID	Title	Description
OG000	Pemetrexed + Erlotinib	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG001	Erlotinib	Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG002	Pemetrexed	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.

Secondary

Probability of OS at 12 Months

OS time is censored at the date of last contact for participants who were still alive or lost to follow-up.

Q-ITT Population: defined as all participants with nonsquamous histology, who were randomized to therapy.

Posted

Number

95% Confidence Interval

percent chance of survival

Month 12

ID	Title	Description
OG000	Pemetrexed + Erlotinib	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG001	Erlotinib	Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
OG002	Pemetrexed	Pemetrexed 500 mg/m^2 of BSA, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0023 events3 affected80 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Arrhythmia	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Myocardial infarction	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Pericardial effusion	Cardiac disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0004 events4 affected78 at risk EG0010 events0 affected83 at risk EG0022 events2 affected80 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Gastritis	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0011 events1 affected83 at risk EG0021 events1 affected80 at risk
Asthenia	General disorders	MedDRA 14.1	Systematic Assessment	EG0003 events2 affected78 at risk EG0012 events2 affected83 at risk EG0021 events1 affected80 at risk
Death	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Irritability	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Mucosal inflammation	General disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Pyrexia	General disorders	MedDRA 14.1	Systematic Assessment	EG0003 events3 affected78 at risk EG0012 events2 affected83 at risk EG0021 events1 affected80 at risk
Sudden death	General disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0021 events1 affected80 at risk
Hepatitis acute	Hepatobiliary disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Abscess	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Bronchitis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Device related infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Herpes zoster	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Pneumonia	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected78 at risk EG0011 events1 affected83 at risk EG0021 events1 affected80 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Respiratory tract infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0014 events3 affected83 at risk EG0020 events0 affected80 at risk
Respiratory tract infection bacterial	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Sepsis	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Subcutaneous abscess	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA 14.1	Systematic Assessment	EG0002 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Haemoglobin decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
White blood cell count decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0011 events1 affected83 at risk EG0021 events1 affected80 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0022 events2 affected80 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected78 at risk EG0010 events0 affected83 at risk EG0024 events4 affected80 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0012 events2 affected83 at risk EG0023 events3 affected80 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0021 events1 affected80 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Metastases to meninges	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Metastatic pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Dizziness	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Hemiplegia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Nervous system disorder	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Neurotoxicity	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Radicular pain	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Renal failure chronic	Renal and urinary disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected78 at risk EG0016 events6 affected83 at risk EG0021 events1 affected80 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0010 events0 affected83 at risk EG0020 events0 affected80 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0022 events2 affected80 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0020 events0 affected80 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Hypertension	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk
Hypotension	Vascular disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0010 events0 affected83 at risk EG0021 events1 affected80 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG00014 events11 affected78 at risk EG0015 events3 affected83 at risk EG0029 events7 affected80 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG00027 events6 affected78 at risk EG0010 events0 affected83 at risk EG00213 events5 affected80 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG00026 events14 affected78 at risk EG0012 events2 affected83 at risk EG00221 events8 affected80 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.1	Systematic Assessment	EG00087 events12 affected78 at risk EG0010 events0 affected83 at risk EG00230 events7 affected80 at risk
Blepharitis	Eye disorders	MedDRA 14.1	Systematic Assessment	EG0004 events4 affected78 at risk EG00116 events11 affected83 at risk EG0020 events0 affected80 at risk
Conjunctivitis	Eye disorders	MedDRA 14.1	Systematic Assessment	EG0005 events4 affected78 at risk EG0011 events1 affected83 at risk EG0021 events1 affected80 at risk
Lacrimation increased	Eye disorders	MedDRA 14.1	Systematic Assessment	EG0005 events4 affected78 at risk EG0014 events4 affected83 at risk EG0024 events4 affected80 at risk
Vision blurred	Eye disorders	MedDRA 14.1	Systematic Assessment	EG0001 events1 affected78 at risk EG0016 events5 affected83 at risk EG0021 events1 affected80 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00011 events5 affected78 at risk EG0015 events5 affected83 at risk EG0023 events3 affected80 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0009 events6 affected78 at risk EG00120 events11 affected83 at risk EG0026 events6 affected80 at risk
Constipation	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00014 events10 affected78 at risk EG0019 events7 affected83 at risk EG00210 events8 affected80 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00065 events29 affected78 at risk EG00170 events29 affected83 at risk EG00210 events8 affected80 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0006 events5 affected78 at risk EG00111 events7 affected83 at risk EG0026 events5 affected80 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG0008 events4 affected78 at risk EG0018 events6 affected83 at risk EG0021 events1 affected80 at risk
Nausea	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00040 events21 affected78 at risk EG00111 events10 affected83 at risk EG00224 events17 affected80 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00049 events15 affected78 at risk EG00115 events9 affected83 at risk EG0021 events1 affected80 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.1	Systematic Assessment	EG00037 events25 affected78 at risk EG00111 events10 affected83 at risk EG00214 events12 affected80 at risk
Asthenia	General disorders	MedDRA 14.1	Systematic Assessment	EG00016 events12 affected78 at risk EG0017 events6 affected83 at risk EG00222 events6 affected80 at risk
Chest pain	General disorders	MedDRA 14.1	Systematic Assessment	EG0004 events4 affected78 at risk EG00112 events12 affected83 at risk EG0023 events3 affected80 at risk
Fatigue	General disorders	MedDRA 14.1	Systematic Assessment	EG00033 events20 affected78 at risk EG00111 events9 affected83 at risk EG00224 events17 affected80 at risk
Mucosal inflammation	General disorders	MedDRA 14.1	Systematic Assessment	EG00027 events14 affected78 at risk EG0018 events7 affected83 at risk EG0025 events3 affected80 at risk
Oedema	General disorders	MedDRA 14.1	Systematic Assessment	EG0003 events3 affected78 at risk EG0011 events1 affected83 at risk EG0024 events4 affected80 at risk
Oedema peripheral	General disorders	MedDRA 14.1	Systematic Assessment	EG00024 events8 affected78 at risk EG0011 events1 affected83 at risk EG0027 events6 affected80 at risk
Pyrexia	General disorders	MedDRA 14.1	Systematic Assessment	EG00021 events11 affected78 at risk EG0014 events3 affected83 at risk EG00214 events9 affected80 at risk
Herpes zoster	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0005 events5 affected78 at risk EG0011 events1 affected83 at risk EG0022 events2 affected80 at risk
Paronychia	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG00011 events7 affected78 at risk EG00116 events14 affected83 at risk EG0020 events0 affected80 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG00010 events7 affected78 at risk EG0018 events4 affected83 at risk EG0023 events3 affected80 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.1	Systematic Assessment	EG0005 events4 affected78 at risk EG0011 events1 affected83 at risk EG0021 events1 affected80 at risk
Alanine aminotransferase increased	Investigations	MedDRA 14.1	Systematic Assessment	EG00019 events13 affected78 at risk EG0011 events1 affected83 at risk EG0029 events8 affected80 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 14.1	Systematic Assessment	EG00019 events12 affected78 at risk EG0015 events3 affected83 at risk EG0028 events7 affected80 at risk
Creatinine renal clearance decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0011 events1 affected83 at risk EG0027 events6 affected80 at risk
Haemoglobin decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG00021 events10 affected78 at risk EG00113 events4 affected83 at risk EG0027 events5 affected80 at risk
Neutrophil count decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG00070 events16 affected78 at risk EG0019 events1 affected83 at risk EG00221 events7 affected80 at risk
Platelet count decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG00011 events6 affected78 at risk EG0010 events0 affected83 at risk EG00220 events5 affected80 at risk
Weight decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG0005 events4 affected78 at risk EG0017 events7 affected83 at risk EG0026 events5 affected80 at risk
White blood cell count decreased	Investigations	MedDRA 14.1	Systematic Assessment	EG00077 events16 affected78 at risk EG00115 events2 affected83 at risk EG00217 events8 affected80 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG00039 events23 affected78 at risk EG00124 events15 affected83 at risk EG00231 events19 affected80 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0009 events8 affected78 at risk EG0014 events4 affected83 at risk EG00210 events7 affected80 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 14.1	Systematic Assessment	EG0007 events5 affected78 at risk EG0015 events4 affected83 at risk EG0026 events6 affected80 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0007 events4 affected78 at risk EG0013 events3 affected83 at risk EG0025 events5 affected80 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0003 events3 affected78 at risk EG0019 events8 affected83 at risk EG0029 events9 affected80 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0007 events4 affected78 at risk EG0015 events3 affected83 at risk EG0026 events3 affected80 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 14.1	Systematic Assessment	EG0006 events5 affected78 at risk EG0018 events5 affected83 at risk EG0024 events4 affected80 at risk
Dizziness	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG00012 events10 affected78 at risk EG0012 events2 affected83 at risk EG0025 events5 affected80 at risk
Headache	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG00016 events14 affected78 at risk EG00111 events8 affected83 at risk EG0025 events5 affected80 at risk
Paraesthesia	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0004 events4 affected78 at risk EG0010 events0 affected83 at risk EG0022 events2 affected80 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 14.1	Systematic Assessment	EG0004 events3 affected78 at risk EG0010 events0 affected83 at risk EG0025 events5 affected80 at risk
Insomnia	Psychiatric disorders	MedDRA 14.1	Systematic Assessment	EG00018 events10 affected78 at risk EG00114 events10 affected83 at risk EG0026 events5 affected80 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG00018 events15 affected78 at risk EG00132 events28 affected83 at risk EG00217 events13 affected80 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG00012 events10 affected78 at risk EG00110 events10 affected83 at risk EG00210 events10 affected80 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0002 events2 affected78 at risk EG00111 events8 affected83 at risk EG0021 events1 affected80 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0006 events5 affected78 at risk EG0012 events1 affected83 at risk EG0021 events1 affected80 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0007 events5 affected78 at risk EG0017 events6 affected83 at risk EG0022 events2 affected80 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 14.1	Systematic Assessment	EG0004 events4 affected78 at risk EG00121 events13 affected83 at risk EG0022 events2 affected80 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG00010 events6 affected78 at risk EG0013 events3 affected83 at risk EG0022 events1 affected80 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0009 events9 affected78 at risk EG0012 events2 affected83 at risk EG0024 events2 affected80 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG00019 events10 affected78 at risk EG0015 events5 affected83 at risk EG0022 events1 affected80 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG00015 events12 affected78 at risk EG00126 events25 affected83 at risk EG0022 events2 affected80 at risk
Nail disorder	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0003 events3 affected78 at risk EG0016 events6 affected83 at risk EG0021 events1 affected80 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG00025 events17 affected78 at risk EG00135 events20 affected83 at risk EG0025 events4 affected80 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG00057 events41 affected78 at risk EG00152 events43 affected83 at risk EG00214 events8 affected80 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0005 events5 affected78 at risk EG00114 events12 affected83 at risk EG0020 events0 affected80 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 14.1	Systematic Assessment	EG0000 events0 affected78 at risk EG0012 events2 affected83 at risk EG0026 events6 affected80 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
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005971	Glutamates
D024342	Amino Acids, Acidic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000600	Amino Acids, Dicarboxylic
D011799	Quinazolines

ID	Title	Description
BG000	Pemetrexed + Erlotinib	Pemetrexed 500 mg/m^2 of body surface area, administered by IV infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
BG001	Erlotinib	Erlotinib 150 mg, administered orally once daily in each 21-day cycle until disease progression or unacceptable toxicity developed or up to 38 months.
BG002	Pemetrexed	Pemetrexed 500 mg/m^2 of body surface area, administered by IV infusion on Day 1 of each 21-day cycle until progression or unacceptable toxicity developed or up to 38 months.
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pemetrexed + Erlotinib	Participants received pemetrexed 500 milligrams per meter squared (mg/m^2) of body surface area, administered by intravenous (IV) infusion on Day 1 plus erlotinib 150 mg orally once daily on Day 2 through Day 14 of each 21 day cycle until disease progression or unacceptable toxicity developed up to 39 months.	25	78	72	78
EG001	Erlotinib	Participants received erlotinib 150 mg, administered orally once daily in each 21 day cycle until disease progression or unacceptable toxicity developed up to 39 months.	18	83	76	83
EG002	Pemetrexed	Participants received pemetrexed 500 mg/m^2 of body surface area, administered by intravenous (IV) infusion on Day 1 of each 21 day cycle until progression or unacceptable toxicity developed up to 39 months.	22	80	67	80