A Study of Pemetrexed, Carboplatin and Bevacizumab in Participants With Nonsquamous Non-Small Cell Lung Cancer

Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive.

Overall Response Rate (ORR) is the number of participants with a Complete Response (CR) and Partial Response (PR) divided by the total number of randomized participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.0) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared to baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions.

Disease Control Rate (DCR) is the number of participants with a Complete Response (CR), Partial Response (PR), and Stable Disease (SD) divided by the total number of randomized participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.0) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared with baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions compared with the smallest sum of the longest diameter recorded since the start of treatment or the appearance of 1 or more new lesion(s). Stable Disease (SD) was defined as small changes that did not meet above criteria.

Progression free survival (PFS) is defined as the time from date of randomization to the date of objective disease progression or death due to any cause. Participants were censored at date of last PFS assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy, whichever was earlier.

Time to progressive disease was defined as the time from randomization to the first date of objective disease progression. Participants were censored at date of last PFS assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy, whichever was earlier.

Safety and toxicity profile was defined as serious and other non-serious adverse events. A summary of serious and all other non-serious adverse events is located in the Reported Adverse Event module.

Length of hospitalization in participants hospitalized during the study or within 30 days of discontinuation regardless of whether the hospitalization was or was not due to study drug.

The FACT-G is a validated instrument used to measure quality of life (QOL) in participants with cancer consisting of the 27-item questionnaire and is organized into subscales, each designed to assess a QOL domain: physical well-being (PWB)-7 items; social/family well-being (SWB)-7 items; emotional well-being (EWB)-6 items; functional well-being (FWB)-7 items. Each item uses a 5 point rating scale (0="not at all" and 4=equals "very much"). FACT-G Total is the sum of the scores of all 4 subscales and ranges from 0 to 108. Higher scores indicate better QOL. Least squares mean (LSmean) change is calculated using the linear-mixed model (LMM) analysis controlled for treatment, baseline value, time point and treatment by time point interaction.

FACT-L is a valid instrument used to measure quality of life (QOL) in participants with cancer consisting of the 27-item FACT-General (G) and 9-item lung cancer subscale (LCS). FACT-G is organized into subscales: physical well-being (PWB)-7 items; social/family well-being (SWB)-7 items; emotional well-being (EWB)-6 items; functional well-being (FWB)-7 items. Each item uses a 5 point rating scale (0="not at all" and 4=equals "very much"). FACT-L Total Score=4 subscales + LCS and ranges from 0 to 144. Trial Outcome Index-Lung (TOI-L)=PWB+FWB+LCS and ranges from 0 to 92. Higher scores indicate better QOL. Least squares mean (LSmean) change is calculated using the linear-mixed model (LMM) analysis controlled for treatment, baseline value, time point and treatment by time point interaction.

FACT/GOG-Ntx is a validated instrument used to measure quality of life (QOL) in participants with cancer and neurotoxicity (Ntx) consisting of 27-item FACT-General (G) and 11-item Ntx subscale. FACT-G is organized into domain subscales: physical well-being (PWB)-7 items; social/family well-being (SWB)-7 items; emotional well-being (EWB)-6 items; functional well-being (FWB)-7 items; each uses a 5 point rating scale (0="not at all" and 4=equals "very much"). FACT/GOG-Ntx Total Score=sum 5 subscales and ranges from 0-152. Ntx Trial Outcome Index (TOI-Ntx)=PWB+FWB+NTX and range from 0-100. For all FACT scales, higher scores indicate better QOL. Least squares mean (LSmean) change is calculated using the linear-mixed model (LMM) analysis controlled for treatment, baseline value, time point and treatment by time point interaction.

Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form.

Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form.

Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form.

Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form.

Epidermal Growth Factor Receptor (EGFR) mutations were measured by polymerase chain reaction (PCR).

Nuclear Thyroid Transcription Factor-1 (TTF-1) expression was measured using an Immunohistochemistry (IHC) assay which were scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system, and H score is a calculated using formula: 1x(percentage of cells stained 1+) + 2x(percentage of cells stained 2+) + 3x(percentage of cells stained 3+). TTF-1 Positive have an H score >0 and TTF-1 Negative have an H score=0. Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive.

Cytoplasmic and nuclear Thymidylate Synthase (TS) expression was measured using an Immunohistochemistry (IHC) assay which were scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic and nuclear staining, and H score was calculated using formula: 1x(percentage of cells stained 1+) + 2x(percentage of cells stained 2+) + 3x(percentage of cells stained 3+). TS Positive have an H score >0 and TS Negative have an H score=0. Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive.

Cytoplasmic and membrane Folate Receptor Alpha (FR-α) expression was measured using an Immunohistochemistry (IHC) assay which were scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic or membrane staining, and H score is a calculated using formula: 1x(percentage of cells stained 1+) + 2x(percentage of cells stained 2+) + 3x(percentage of cells stained 3+). FR-α Positive have an H score >0 and FR-α Negative have an H score=0. Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive.