Comparative effectiveness of pembrolizumab-chemotherapy versus chemotherapy with/without bevacizumab in unresectable, locally advanced or metastatic non-small cell lung cancer: a Chinese multicenter real-world analysis emphasizing PD-L1-negative populations.

Abstract

Background: Current limited evidence suggests that the use of pembrolizumab combined with chemotherapy may be effective for treatment-naïve patients with metastatic non-small cell lung cancer (NSCLC) and negative programmed cell death ligand 1 (PD-L1) expression, but real-world data are relatively scarce. This retrospective cohort study analyzed the efficacy, adverse events, and prognostic factors in these patients treated with chemotherapy with or without pembrolizumab.

Methods: This retrospective study analyzed the data of patients with unresectable, locally advanced or metastatic NSCLC without sensitive epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) or proto-oncogene receptor tyrosine kinase (ROS1) alterations who had negative PD-L1 expression and received first-line pembrolizumab plus chemotherapy (the Pembro group) or platinum-based dual chemotherapy with or without bevacizumab (the Chemo group). The efficacy outcomes and safety profiles of the two groups were compared.

Results: The study included 246 patients (Pembro group, n=114; Chemo group, n=132). The median follow-up period was 28.3 months. The Pembro group significantly prolonged progression-free survival (PFS) compared with the Chemo group [9.5 months, 95% confidence interval (CI): 7.5-11.5 vs. 7.2 months, 95% CI: 5.7-8.7; hazard ratio (HR) =0.64, 95% CI: 0.46-0.87; P=0.004]. Squamous cell lung cancer (SCC) patients demonstrated substantial PFS benefit (13.8 months, 95% CI: 3.2-24.1 vs. 4.8 months, 95% CI: 3.4-6.2; P<0.001), while non-SCC patients showed comparable PFS (9.3 months, 95% CI: 7.6-11.0 vs. 8.0 months, 95% CI: 6.0-10.0; P=0.56). Overall survival (OS) favored the Pembro group (21.2 months, 95% CI: 16.0-26.4 vs. 20.1 months, 95% CI: 15.5-24.7; HR =0.71, 95% CI: 0.50-1.00; P=0.052). The SCC patients in the Pembro group demonstrated a significant survival benefit with a median OS that was not reached, compared to 14.2 months (95% CI: 6.3-22.1) in the chemo group (HR =0.42, 95% CI: 0.22-0.78; P=0.007). Grade ≥3 non-immune-related adverse events (non-irAEs) occurred more often in the Pembro group (46.8%) than the Chemo group (33.1%, P=0.03). Moreover, 45 (39.5%) patients experienced 63 irAEs, and no grade 5 or new irAEs were observed.

Conclusions: Pembrolizumab combined with chemotherapy may prolong survival in patients with PD-L1-negative advanced NSCLC, particularly those with squamous histology.