Study of Enzastaurin Versus Placebo With Pemetrexed for Participants With Advanced or Metastatic Lung Cancer

PFS was defined as the time from date of randomization to the first documented observation of disease progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. PFS was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death at the data inclusion cut-off date.

Time frame: Baseline to measured progressive disease up to 9.92 months

Population: All randomized participants. Twenty five (25) participants in Pemetrexed + Enzastaurin group and twenty three (23) participants in Pemetrexed + Placebo group were censored for analysis.

DDC was defined as the time from randomization to the first documented observation of disease progression or death from any cause and was limited to the participants with a best tumor response of complete response (CR), partial response (PR), or stable disease (SD). Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions or the appearance of new lesions. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. SD was defined as small changes that did not meet the above criteria. DDC was censored at the date of the last objective progression-free disease assessment for participants who did not experience PD or death.

Time frame: Baseline to measured progressive disease up to 9.92 months

Population: Randomized participants who received at least 1 dose of study drug and had a best tumor response of CR, PR, or SD. Fourteen (14) participants in Pemetrexed + Enzastaurin group and seventeen (17) participants in Pemetrexed + Placebo group were censored for analysis.

OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the date the participant was last known to be alive.

Time frame: Baseline to date of death from any cause up to 12.32 months

Population: All randomized participants. Fifty three (53) participants in Pemetrexed + Enzastaurin group and forty five (45) participants in Pemetrexed + Placebo group were censored for analysis.

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Participants with a best response of complete response (CR) or partial response (PR) were considered to have had a tumor response. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants was calculated as the total number of participants affected divided by the number of participants analyzed then multiplied by 100.

Time frame: Baseline to measured progressive disease up to 9.92 months

Population: Randomized participants who received at least 1 dose of study drug and had responses evaluated for CR or PR.

LCSS is a participant rated lung cancer instrument which consisted of 6 disease related symptoms (appetite, cough, fatigue, dyspnea, hemoptysis, and pain) and 3 quality of life (QoL) items (activity status, symptomatic distress, and overall QoL). TW in LCSS-HRQoL was measured from the date of enrollment to the first date of a 15 millimeters (mm) worsening in the 9th LCSS item on QoL. LCSS-HRQoL was measured on the 100-mm visual analogue scale (VAS) with the scores ranging from 0 (best response and very high HRQoL) to 100-mm (worse response and very low HRQoL). TW-HRQoL was censored at the date of the participant's last LCSS assessment for participant without a 15-mm increase on the 100-mm VAS.

Time frame: Baseline to disease worsening up to 10.58 months

Population: Randomized participants who had at least 1 baseline and 1 postbaseline LCSS assessment for HRQoL. Thirty (30) participants in Pemetrexed + Enzastaurin group and forty (40) participants in Pemetrexed + Placebo group were censored for the analysis.

Protein expression was measured using an Immunohistochemistry (IHC) assay from the tumor tissue samples. IHC histo-scores (H-scores) were determined separately for each of the 3 biomarkers: folate receptor alpha (FR alpha) in cytoplasm and apical membrane, thymidylate synthase (TS) in cytoplasm and nucleus, and thyroid transcription factor-1 (TTF1) in the nucleus. Tumor tissue samples were to be scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic and nuclear staining. IHC H-score was calculated using the formula: 1 \* (percentage of cells stained 1+) + 2 \* (percentage of cells stained 2+) + 3 \* (percentage of cells stained 3+), giving a minimum score of 0 to a maximum score of 300. The maximum score indicates the strongest expression.

Time frame: Tumor samples collected at baseline

Population: Randomized participants who had at least 1 biomarker expression value measured at baseline.

Reported are the deaths due to study disease and adverse events (AEs) that occurred during the 30 days after treatment discontinuation.

Time frame: End of study treatment [16 Cycles (21-day cycles, except Cycle 1 [28 days])] through 30 days after treatment discontinuation

Population: All randomized participants who received at least 1 dose of study drug.

Reported are the deaths due to study disease and adverse events (AEs) that occurred while on study treatment.

Time frame: Baseline through study completion [up to 16 Cycles (21-day cycles, except Cycle 1 [28 days])]

Population: All randomized participants who received at least 1 dose of study drug.