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.