Background: Pembrolizumab-based therapy is a standard first-line option for advanced non-small-cell lung cancer (NSCLC), yet pivotal clinical-trial populations may not reflect patients encountered in routine practice. Real-world cohorts enriched for Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 and high metastatic burden remain underreported. We assessed real-world outcomes of first-line pembrolizumab in a heterogeneous cohort enriched for these. Methods: Retrospective cohort analysis of 45 patients with advanced NSCLC who received first-line pembrolizumab-based therapy (monotherapy or with platinum-based chemotherapy) at a single health maintenance organization in Israel between September 2017 and April 2020. Results: Mean age was 69.3 years (SD 9.0), 82.2% were male, 91.1% were current or former smokers, 37.8% had ECOG PS ≥2 (including 17.8% with ECOG ≥3), and 53.3% had three or more metastatic organ sites. PD-L1 expression was ≥50% in 46.7%, 1–49% in 13.3%, and <1% in 22.2%. After a median follow-up of 48.7 months (88.9% event rate), median overall survival (OS) was 8.87 months (95% CI, 5.88–14.32) and median progression-free survival (PFS) was 4.20 months (95% CI, 2.76–6.18), with an objective response rate of 46.7% and a disease control rate of 68.9%. On univariate Cox regression, the number of metastatic sites was most strongly associated with OS (HR 1.41 per site, 95% CI, 1.17–1.70, p = 0.0003). PD-L1 expression was significantly associated with both PFS (p < 0.0001) and OS (p = 0.0012), with the longest survival observed in patients with PD-L1 ≥50%. Conclusions: In this real-world cohort enriched for poor performance status and high metastatic burden, pembrolizumab-based therapy provided clinical benefit, but observed survival was substantially shorter than that reported in pivotal trials.
Koren et al. (2026) studied this question.