First-line taxane-versus pemetrexed-based chemoimmunotherapy for TTF-1–negative nonsquamous non–small cell lung cancer: a propensity score–matched study

Background Nonsquamous non–small cell lung cancer (NSCLC) negative for thyroid transcription factor–1 (TTF-1) has a poor prognosis and limited sensitivity to pemetrexed-based regimens. We performed a propensity score–matched analysis to compare atezolizumab plus carboplatin and nab-paclitaxel versus pembrolizumab plus platinum and pemetrexed as first-line therapy for such patients. Methods We analyzed patients with TTF-1–negative advanced nonsquamous NSCLC treated with atezolizumab plus carboplatin and nab-paclitaxel in a prospective, multicenter phase II trial and those treated with pembrolizumab plus platinum and pemetrexed in a retrospective real-world cohort. Propensity score matching was performed to balance prespecified baseline covariates. Progression-free survival (PFS), overall survival (OS), and the objective response rate (ORR) were compared between the two matched treatment groups. Results Among the matched cohort ( n =94), median PFS was 4.6 months for atezolizumab with carboplatin plus nab-paclitaxel and 5.4 months for pembrolizumab with platinum plus pemetrexed (HR, 0.91 [95% CI, 0.57–1.45]), whereas median OS was 18.4 and 21.0 months (HR, 1.01 [95% CI, 0.59–1.73]) and the ORR was 56.5% and 42.6%, respectively. Sensitivity analysis with inverse probability of treatment weighting for PFS in the overall and matched cohorts yielded effect estimates consistent with the primary analysis. Conclusions This study is the first propensity score–matched comparison of these two regimens for TTF-1–negative nonsquamous NSCLC. Although atezolizumab with carboplatin plus nab-paclitaxel showed a numerically higher ORR, no statistically significant difference in PFS or OS was detected between the two regimens. Trial Registration University Hospital Medical Information Network Clinical Trials Registry (UMIN000057827).