First-line pembrolizumab for metastatic NSCLC in lower-middle-income countries: bridging the efficacy-effectiveness gap

Pembrolizumab is a standard first-line therapy for advanced/metastatic non-small cell lung cancer (a/mNSCLC) lacking actionable mutations. Data from lower-middle-income countries (LMICs) remain scarce. From January 2019 to June 2024, we prospectively analyzed 78 a/mNSCLC patients receiving pembrolizumab-based first-line therapy. Endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and conditional survival probabilities. With a median follow-up of 27 months, median OS was 21 months (95% CI: 12.2-30.8) and median PFS 6.3 months (95% CI: 5.5-10.1). At first response evaluation (2 months), partial response was seen in 47.4% (37/78), stable disease in 16.7% (13/78). Next-generation sequencing (85% tested) revealed non-actionable mutations in 70%; notably, 4 of 6 long-term survivors harbored KRAS mutations. PD-L1 TPS ≥ 50% significantly lowered progression and mortality risk. Age, performance status (ECOG), and disease response significantly influenced the OS. The conditional survival probability for an additional 6 months after surviving the first 6 months was 78.1% (90% in patients with controlled disease). Real-world LMIC data demonstrated comparable effectiveness of pembrolizumab-based therapy in a/mNSCLC despite a higher proportion of adverse prognostic factors. More studies in diverse clinical settings are needed to provide a reliable estimate of benefit.