PD-1 inhibitor plus chemotherapy versus bevacizumab plus chemotherapy in patients with advanced non-squamous non-small-cell lung cancer: a pooled analysis of three randomised trials

Background To date, none of randomised trials aim to compare the efficacy of programmed death 1 (PD-1) inhibitor plus chemotherapy and bevacizumab plus chemotherapy as first-line treatment for non-squamous non-small-cell lung cancer (NSCLC). This analysis pooled prospective data to compare the survival benefits of the two regimens for advanced NSCLC without targetable genetic mutations. Methods Data were pooled from three randomised phase III clinical trials: NCT03607539 , NCT03134872 and NCT02954172 . 466 patients received PD-1 inhibitor (200 mg) plus pemetrexed (500 mg/m²) and platinum (cisplatin 75 mg/m 2 or carboplatin area under the curve (AUC) 5 mg/mL/min), while 432 patients received bevacizumab (15 mg/kg) plus paclitaxel (175 mg/m 2 ) and carboplatin (AUC 6 mg/mL/min). Propensity score matching in a 1:1 ratio was performed to balance baseline characteristics of the two arms. The endpoints of this analysis were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Results In total, 375 patients in each arm were matched. With a median follow-up of 23 months (IQR 21–26), results showed that median PFS was significantly prolonged in the PD-1 inhibitor arm than in the bevacizumab arm (10.1 vs 7.4 months; HR 0.62, 95% CI 0.52 to 0.73, p<0.001). Improved OS was also demonstrated in the PD-1 inhibitor arm (27.9 vs 20.2 months; HR 0.75 95% CI 0.61 to 0.91, p=0.004). ORR in the PD-1 inhibitor arm was 56.8%, while that in the bevacizumab arm was 45.1%. However, exploratory subgroup analysis indicated that median PFS and median OS of the two arms were comparable in patients with negative programmed death ligand 1 expression or in patients aged ≥65 years old. Conclusions PD-1 inhibitor plus chemotherapy was associated with significant survival benefits compared with bevacizumab plus chemotherapy in patients with advanced non-squamous NSCLC, which provides evidence support to guide clinical practice. Nonetheless, the comparative survival outcomes in several subgroups indicated that bevacizumab plus chemotherapy still mattered.