Study of Taxane/Carboplatin +/- Cetuximab as First-Line Treatment for Patients With Advanced/Metastatic Non-Small Cell Lung Cancer

Interval between randomization date & earliest date of disease progression/death due to any cause, assessed by the Independent Radiology Review Committee (IRRC) using modified World Health Organization (WHO) criteria to define progressive disease (PD): \>=25% increase in sum of products of diameters (SOPD) of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion. If no progression/death, date of last tumor assessment used. For participants who had no on-study tumor assessments & were still alive, date of randomization used.

Time frame: From randomization to evidence of disease progression/death or date of last tumor assessment (up to 26 months).

Population: All randomized participants (intention to treat population).

Median number of months of response (time from first occurrence of CR/PR to date of PD/death, \[per IRRC assessment,using modified WHO criteria\]) calculated for participants whose best response=CR/PR.For participants who did not progress/die, date of last tumor assessment used.CR:disappearance of all index/non-index lesions;PR:\>= 50% reduction in SOPD of index lesions compared with baseline, no evidence of progression.No new lesions present.PD:\>=25% increase in SOPD of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion.

Time frame: Time from first occurrence of CR or PR (whichever was recorded first) to the date of PD, death or date of last tumor assessment (up to 19 months).

Population: All randomized participants with a best response of CR or PR.

The median number of months of survival was defined as the time from randomization to the date of death. For participants who did not die, the date of last contact was used.

Time frame: From randomization to death or date of last contact (up to 41 months).

Population: All randomized participants (intention to treat population).

The median number of months to response was calculated for participants whose best response was CR or PR. It was defined as the time from the first dose of study therapy to the first date that criteria for PR or CR (whichever occurred first)were met. Response was assessed by the IRRC, using the modified WHO criteria: CR: disappearance of all index/non-index lesions; PR: \>= 50% reduction in the SOPD of index lesions compared with the baseline SOPD, with no evidence of progression. To qualify as CR or PR, no new lesions could be present.

Time frame: Time from first dose of study therapy to the date of PR or CR, whichever occurred first (up to 13 months).

Population: All randomized participants with a best response of CR or PR.

Symptoms were assessed using the FACT-LCS questionnaire. This 7-item scale has scores ranging from 0 (severely symptomatic) to 28 (symptom-free). Symptomatic progression was defined as \>= 2-point decrease from baseline in score (maintained for 2 consecutive assessments at least 3 weeks apart). Time to symptomatic progression was defined as the time from randomization to date of symptoms worsening. For participants with no symptom progression, the date of the last symptom assessment was used. See also Outcome Measure 15.

Time frame: From randomization to evidence of disease progression/death or date of last symptom assessment (up to 33 weeks).

Population: All randomized participants who completed baseline FACT-LCS questionnaire (ie, completed questionnaire \<=14 days prior to treatment, or if they were never treated, \<=14 days prior to randomization) and who had a baseline score greater than or equal to 2. As the median was not reached, no data are presented here (see Outcome Measure 15).

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). The results presented are stratified according to which drug was discontinued.

Time frame: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

Population: All treated participants.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs that were categorized under the composite term acneform rash were of particular importance. These AEs were: rash, rash pustular, rash erythematous, dermatitis acneiform, dermatitis exfoliative, rash papular, rash pruritic, rash generalised, rash macular, rash maculo-papular, acne, acne pustular, skin desquamation and dry skin.

Time frame: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

Population: All treated participants.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs that were categorized under the composite term cardiac AE were of particular importance. These AEs, coded as preferred or other level Medical Dictionary for Regulatory Activities \[MedDRA\] terms were: coronary artery disorders, cardiac arrhythmias, heart failures not elsewhere classified, left ventricular failures, sudden cardiac death, cardiac death and sudden death.

Time frame: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

Population: All treated participants.

AE=any new untoward medical occurrence or worsening of pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs that were categorized under the composite term infusion reaction were of particular importance. These AEs were: infusion-related reaction, hypersensitivity, anaphylactic reaction, anaphylactic shock, and anaphylactoid reaction regardless of when they occurred. The terms dyspnea, pyrexia and chills were also grouped under infusion reaction, provided the onset date of these toxicities occurred on the first day of study treatment.

Time frame: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

Population: All treated participants.

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). An SAE was defined as an AE that resulted in death, was life-threatening, required hospitalization (or prolongation of existing hospitalization), or was an important medical event.

Time frame: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

Population: All treated participants. The AEs represented here include SAEs, which are not included in the AE count represented in the AE xml upload section. As such, these numbers may not match.

Abnormalities were graded according to the NCI CTC, version 3.0. The scale is graded from 1 (least severe) to 4 (life threatening). Grade 3 and 4 criteria are defined as follows: Hyperglycemia (non-fasting): Grade 3, serum glucose \>13.9 - 27.8 mmol/L; Grade 4 \>27.8 mmol/L or acidosis. Hypomagnesemia: Grade 3, serum magnesium \>1.23 - 3.30 mmol/L; Grade 4 \>3.30 mmol/L. Hyponatremia: Grade 3, serum sodium \<130 - 120 mmol/L; Grade 4 \<120 mmol/L. Low albumin: Grade 3, serum albumin \<20 g/L; Grade 4 not applicable.

Time frame: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

Population: All treated participants.

Abnormalities were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0. The scale is graded from 1 (least severe) to 4 (life threatening). Grade 3 and 4 criteria are defined as follows: Neutropenia: Grade 3, neutrophils \<1.0 - 0.5 x 10\^9/L; Grade 4, \<0.5 x 10\^9/L. Leukopenia: Grade 3, leukocytes \<2.0 - 1.0 x 10\^9/L; Grade 4, \<1.0 x 10\^9/L. Thrombocytopenia: Grade 3, platelets \<50.0 - 25.0 x 10\^9/L; Grade 4, \<25.0 x 10\^9/L. Anemia: Grade 3, hemoglobin \<4.9 - 4.0 millimoles (mmol)/L, Grade 4, \<4.0 mmol/L.

Time frame: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

Population: All treated participants.

Participants were to complete log to collect information on unscheduled visits to physicians,clinics,hospitals & other unscheduled major procedures.If asked, participants were to complete and return log to site upon routinely scheduled visits.The purpose of this exploratory analysis was to understand the economical implications as a secondary objective.This was not a pivotal study & therefore not needed to support any arguments with regulatory authorities concerning cost-benefit,hence,it was not necessary to conduct this analysis. There is no intent on conducting this analysis in the future.

Time frame: Day 1 of each cycle of treatment, at the end of study therapy evaluation and at the first follow-up visit (6 weeks after the end of study therapy evaluation).

Population: This analysis was not performed.

Tumor response was defined as the number of participants whose best response was CR or PR, per the IRRC assessment, using the modified WHO criteria: CR: disappearance of all index/non-index lesions; PR: \>= 50% reduction in the SOPD of index lesions compared with the baseline SOPD, with no evidence of progression. To qualify as CR or PR, no new lesions could be present.

Time frame: From randomization to end of study drug therapy (up to 174 weeks).

Population: All randomized participants (intention to treat population).

Disease control was defined as the number of participants whose best response was CR, PR, or SD, per the IRRC assessment, using the modified WHO criteria: CR: disappearance of all index/non-index lesions; PR:\>= 50% reduction in the SOPD of index lesions compared with the baseline SOPD, with no evidence of progression (to qualify as CR or PR, no new lesions could be present); SD: participants who did not meet the criteria for CR, PR, or PD (PD:\>=25% increase in SOPD of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion).

Time frame: From randomization to end of study drug therapy (up to 174 weeks).

Population: All randomized participants (intention to treat population).

Symptoms were assessed using the Functional Assessment of Cancer Therapy - Lung Cancer Subscale (FACT-LCS) questionnaire. This 7-item scale has scores ranging from 0 (severely symptomatic in all symptoms assessed) to 28 (symptom-free on all symptoms assessed). Symptom response (improvement) was defined as \>= 2-point increase from baseline in score (maintained for 2 consecutive assessments, at least 3 weeks apart). Participants with a baseline score of \>= 27 were not evaluable, as it would not have been possible to show an improvement. Participants with no baseline data were also not evaluable.

Time frame: From randomization to evidence of disease progression/death or date of last symptom assessment (up to 33 weeks).

Population: All randomized participants who completed a baseline FACT-LCS questionnaire (ie, who completed a questionnaire \<=14 days prior to treatment, or if they were never treated, \<=14 days prior to randomization) and who had a baseline score of 26 or less.

Symptoms were assessed using the FACT-LCS questionnaire. This 7-item scale has scores ranging from 0 (severely symptomatic) to 28 (symptom-free). The median change from baseline score was calculated at 3-weekly intervals. See also Outcome Measure 8.

Time frame: From randomization to evidence of disease progression/death or date of last symptom assessment (up to 33 weeks).

Population: All randomized participants who completed a baseline FACT-LCS questionnaire (ie, completed questionnaire \<=14 days prior to treatment, or if they were never treated, \<=14 days prior to randomization). n = number of participants with a score at both the baseline and at the specified time point (each arm respectively).