Comparative real-world survival of first-line atezolizumab, nivolumab, and pembrolizumab in older patients with metastatic non-small cell lung cancer.

[BACKGROUND] Although immune checkpoint inhibitors (ICIs) have significantly improved overall survival (OS) for patients with metastatic non-small cell lung cancer (mNSCLC), there is a paucity of comparative effectiveness evidence to inform optimal first-line treatment selection.

[OBJECTIVE] To compare OS among older patients with mNSCLC who received first-line atezolizumab, nivolumab, or pembrolizumab.

[METHODS] This retrospective cohort study used the 2014-2020 Surveillance, Epidemiology, and End Results-Medicare data and included patients aged 66 years or older, diagnosed with mNSCLC, and treated with first-line atezolizumab, nivolumab, or pembrolizumab. OS was compared using unadjusted, multivariable-adjusted, and propensity score matching (PSM) Cox proportional hazards models. Sensitivity and subgroup analyses by patient histology (squamous and nonsquamous) were also conducted.

[RESULTS] The study cohort included 4,635 patients, 112 treated with atezolizumab, 251 with nivolumab, and 4,272 with pembrolizumab. Pembrolizumab was associated with a significant survival advantage compared with atezolizumab (multivariable-adjusted hazard ratio [HR], 0.67; 95% CI, 0.53-0.84; PSM HR, 0.69; 95% CI, 0.54-0.87) and nivolumab (multivariable-adjusted HR, 0.83; 95% CI, 0.69-0.99) in both main analyses and sensitivity analyses. The OS difference between nivolumab and atezolizumab was inconclusive (multivariable-adjusted HR, 0.73; 95% CI, 0.46-1.16; PSM HR, 0.65; 95% CI, 0.41-1.04). In subgroup analyses, differences in OS between pembrolizumab and nivolumab were not observed among patients with squamous histology (multivariable-adjusted HR, 0.85; 95% CI, 0.65-1.11; PSM HR, 1.15; 95% CI, 0.89-1.49).

[CONCLUSIONS] In this population-based study, first-line pembrolizumab was associated with a significant OS benefit compared with atezolizumab and nivolumab among older adults with mNSCLC. For patients with squamous histology, OS differences between pembrolizumab and nivolumab were not observed. These findings support pembrolizumab as the preferred first-line treatment for older patients with mNSCLC, while highlighting the need for further investigation into the effectiveness of nivolumab specifically within squamous histology subgroups.