Comparative Effectiveness of Atezolizumab, Nivolumab and Pembrolizumab in Second-Line Treatment of Advanced Non-Small...

This observational study aimed to assess the comparative effectiveness of immunotherapy (IO) in the second-line setting of advanced non-small cell lung cancer (aNSCLC).

Population-based data was obtained from the Cancer Registry of Norway (CRN) and linked with the hospital data from the Norwegian Patient Registry (NPR) and treatment data from the Norwegian Prescribed Drug Registry (NorPD). Adult patients with aNSCLC diagnosis in Norway in 2015-2021 were included. The final cohort included patients using IO in the second-line setting after first-line treatment with platinum-containing doublet chemotherapy. We performed a target trial emulating key eligibility criteria commonly used in aNSCLC randomised clinical trials (RCTs) and constructed three pair-wise 1:1 propensity score (PS)-matched comparison cohorts: atezolizumab versus pembrolizumab, atezolizumab versus nivolumab and nivolumab versus pembrolizumab. Age, sex, morphology, ECOG performance status, PD-L1 expression level, chemoradiation use and comorbidities were included in the PS. The primary outcome was overall survival (OS). Patients were followed until experiencing death, emigration or end of study. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Analyses included a total of 447 patients, 206 treated with atezolizumab, 71 nivolumab and 170 pembrolizumab. The median follow-up time was 8.4 (IQR: 3.4-20.7) months. We found no evidence of significant differences in OS in any of the three pair-wise comparisons; atezolizumab versus pembrolizumab (HR: 0.86; 95% CI: 0.65-1.12), atezolizumab versus nivolumab (HR: 0.97; 95% CI: 0.68-1.37) and nivolumab versus pembrolizumab (HR: 0.99; 95% CI: 0.67-1.49).

The study suggests no evidence of significant differences between the three IO drugs atezolizumab, nivolumab and pembrolizumab when used in second-line aNSCLC. However, wide CIs and moderate sample sizes limit definitive conclusions. These results highlight the need for larger studies to confirm potential equivalence or detect meaningful differences.