Long-term survival comparison of first-line pembrolizumab versus pembrolizumab plus chemotherapy for patients with advanced non-small cell lung cancer: A multicenter propensity-matched cohort study

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BACKGROUND: Pembrolizumab is currently used as a first-line therapy for EGFR- and ALK-negative advanced non-small cell lung cancer (NSCLC). However, whether pembrolizumab alone (P-mono) or combined with platinum chemotherapy (P-combo) provides superior long-term benefit remains unclear. METHODS: We retrospectively analyzed 392 patients with PD-L1 TPS ≥ 1 % treated first-line with P-mono (n = 194) or P-combo (n = 198) between 2019 and 2021. Propensity-score matching across 13 baseline variables yielded two well-balanced cohorts of 97 patients each, with a median follow-ups of 42.8 and 44.1 months, respectively. RESULTS: P-combo prolonged overall survival (OS) (median 31.8 vs 20.7 months; hazard ratio [HR] 0.67, 95 % confidence interval [CI] 0.46-0.96) and progression-free survival (12.5 vs 7.0 months; HR 0.59, 95 %CI 0.43-0.81). The 3- and 4-year OS rates were 49.8 % and 42.7 %, respectively, with P-combo, compared with 28.1 % and 22.3 % with P-mono. The 48-month restricted mean survival time also favored P-combo (p = 0.039). Additionally, greater benefits were observed among patients aged < 75 years, with ECOG performance status 0-1, PD-L1 TPS 1-49 %, and those using proton-pump inhibitors. Grade ≥ 3 treatment-related adverse events (TRAEs) were more frequent with P-combo (35 % vs 20 %, p = 0.024). However, treatment-related deaths (2 % each) and pneumonitis incidence and severity were comparable; cumulative toxicity curves plateaued after 3 years. CONCLUSIONS: These findings suggest that P-combo showed a durable survival advantage over monotherapy and acceptable TRAEs in patients with PD-L1-positive NSCLC, identifying clinical subgroups most likely to benefit. Prospective randomized trials are warranted to validate these observations and guide optimal first-line treatment strategies.

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