PD-1/PD-L1 inhibitors plus chemotherapy versus chemotherapy alone for TKIs-resistant, EGFR-Mutant, advanced non-small-cell lung cancer: a phase 3 RCTs based meta-analysis.

Background: Immunotherapy combined with chemotherapy has emerged as a potential strategy to overcome tyrosine kinase inhibitors (TKIs)-resistant for advanced non-small-cell lung cancer (NSCLC); however, the efficacy and safety of PD-1/PD-L1 inhibitors plus chemotherapy (PIC) compared to chemotherapy alone require further investigation.

Research design and methods: Phase III randomized controlled trials (RCTs) were systematically searched from 6 databases. Pooled hazard ratios (HRs) for survival outcomes and risk ratios (RRs) for responses and adverse events (AEs) were calculated.

Results: Three phase III RCTs were included in the final analysis. The PIC therapy significantly improved overall survival (OS) (HR: 0.86, 95% CI: 0.75-1.00, p = 0.04) and progression-free survival (PFS) (HR: 0.78, 95% CI: 0.68-0.90, p = 0.0005) compared to chemotherapy alone. While PIC therapy improved survival in the overall population, no significant benefit was observed for patients with brain metastases and non-sensitizing EGFR mutations. However, the incidence of immune-related AEs (irAEs) (RR: 2.02, 95% CI: 1.45-2.81, p < 0.0001) and grade 3-5 irAEs (RR: 2.02, 95% CI: 1.03-3.98, p = 0.04) were increased.

Conclusions: PIC therapy may provide a survival benefit for patients with TKIs-resistant, EGFR-mutant advanced NSCLC. Moreover, this potential benefit should be weighed against the increased risk of irAEs.

Registration: PROSPERO (CRD42024615907).