Statistical analysis
NSCLC, SD
ADVERSE EVENTS, ADENOCARCINOMA, NSCLC, EVENTS, PATHOLOGY
The primary endpoint of this study was progression‐free survival (PFS) from randomization. Secondary endpoints were the objective response rate (ORR), overall survival (OS) from randomization, and adverse events. The sample size was calculated with a one‐sided significance level of 0.05 and 80% statistical power using the case number design of Lachin and Foulkes.All data of this study were maintained in the TORG coordinating office, which was independent of the attending physicians and institutions. All data maintained in the TORG coordinating office were not available to attending physicians. The entries of all patients were conducted by physicians and assistants at each institution. The random allocation was stratified by response to induction therapy (SD, PR, and CR), pathology (adenocarcinoma vs. non‐adenocarcinoma), PS (0 vs. 1), and institution. The minimization method was applied to balance the distribution of prognostic factors between the pemetrexed group and the pemetrexed plus bevacizumab group. Zelen's method was used to balance the number of patients allocated to the two groups.Although this study proceeded with the above settings, the combination of immune checkpoint‐inhibitor and chemotherapy has been the standard first‐line therapy for advanced NSCLC since January 2019. It was expected that it would be difficult to collect new cases after 2019 in Japan; therefore, the sample size was re‐calculated with a one‐sided significance level of 0.10 and statistical power of 80% at December 2018. In this setting, a sample size of 54 patients was estimated to achieve the desired statistical power, and events in 52 of 54 patients were needed to estimate the primary endpoint. In addition, 66 patients were randomized at December 2018. Due to these circumstances, case entry was conducted until March 2019 without opening the data. When events occurred in 52 patients, all data were analyzed.