62P 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 randomized trials

BackgroundTo date, none of randomized 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.MethodsData were pooled from three randomized phase III clinical trials: NCT03607539, NCT03134872 and NCT02954172. 466 patients received PD-1 inhibitor (200mg) plus pemetrexed (500 mg/m2) and platinum (cisplatin 75 mg/m 2 or carboplatin AUC 5 mg/mL/min) while 432 patients received bevacizumab (15 mg/kg) plus paclitaxel (175 mg/m2) 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).ResultsTotally, 375 patients in each arm were matched. With a median follow-up of 23 months (IQR 21-26), median PFS was significantly prolonged in the PD-1 inhibitor arm than in the bevacizumab arm (10.1 vs 7.4 months, hazard ratio [HR] 0.62, [95% CI 0.52-0.73], p<0.001). Improved OS was also demonstrated in PD-1 inhibitor arm (27.9 versus 20.2 months, HR 0.75, [0.61-0.91], p=0.004). ORR in PD-1 inhibitor arm was 56.8% while 45.1% in bevacizumab arm. However, exploratory subgroup analysis indicated that median PFS and median OS of the two arms were comparable in patients with negative PD-L1 expression, or patients aged ≥ 65 years old.ConclusionsPD-1 inhibitor plus chemotherapy was associated with significant survival benefits compared to bevacizumab plus chemotherapy in patients with advanced non-squamous NSCLC, which could provide evidence support to guide clinical practice. Nonetheless, the comparative survival outcomes in several subgroups indicated that bevacizumab plus chemotherapy still mattered.Clinical trial identificationNCT03607539, NCT03134872, NCT02954172.Legal entity responsible for the studyShandong Cancer Hospital.FundingJiangsu Hengrui Medicine and Innovent Biologics, Inc.DisclosureX. Meng: Financial Interests, Personal, Invited Speaker: Innovent Biologics, Inc. L. Xing: Financial Interests, Personal, Invited Speaker: Innovent Biologics, Inc. L. Zhang: Financial Interests, Personal, Invited Speaker: Innovent Biologics, Inc. C. Zhou: Financial Interests, Personal, Invited Speaker: Jiangsu Hengrui Medicine. J. Yu: Financial Interests, Personal, Invited Speaker: Jiangsu Hengrui Medicine. All other authors have declared no conflicts of interest. BackgroundTo date, none of randomized 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. To date, none of randomized 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. MethodsData were pooled from three randomized phase III clinical trials: NCT03607539, NCT03134872 and NCT02954172. 466 patients received PD-1 inhibitor (200mg) plus pemetrexed (500 mg/m2) and platinum (cisplatin 75 mg/m 2 or carboplatin AUC 5 mg/mL/min) while 432 patients received bevacizumab (15 mg/kg) plus paclitaxel (175 mg/m2) 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). Data were pooled from three randomized phase III clinical trials: NCT03607539, NCT03134872 and NCT02954172. 466 patients received PD-1 inhibitor (200mg) plus pemetrexed (500 mg/m2) and platinum (cisplatin 75 mg/m 2 or carboplatin AUC 5 mg/mL/min) while 432 patients received bevacizumab (15 mg/kg) plus paclitaxel (175 mg/m2) 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). ResultsTotally, 375 patients in each arm were matched. With a median follow-up of 23 months (IQR 21-26), median PFS was significantly prolonged in the PD-1 inhibitor arm than in the bevacizumab arm (10.1 vs 7.4 months, hazard ratio [HR] 0.62, [95% CI 0.52-0.73], p<0.001). Improved OS was also demonstrated in PD-1 inhibitor arm (27.9 versus 20.2 months, HR 0.75, [0.61-0.91], p=0.004). ORR in PD-1 inhibitor arm was 56.8% while 45.1% in bevacizumab arm. However, exploratory subgroup analysis indicated that median PFS and median OS of the two arms were comparable in patients with negative PD-L1 expression, or patients aged ≥ 65 years old. Totally, 375 patients in each arm were matched. With a median follow-up of 23 months (IQR 21-26), median PFS was significantly prolonged in the PD-1 inhibitor arm than in the bevacizumab arm (10.1 vs 7.4 months, hazard ratio [HR] 0.62, [95% CI 0.52-0.73], p<0.001). Improved OS was also demonstrated in PD-1 inhibitor arm (27.9 versus 20.2 months, HR 0.75, [0.61-0.91], p=0.004). ORR in PD-1 inhibitor arm was 56.8% while 45.1% in bevacizumab arm. However, exploratory subgroup analysis indicated that median PFS and median OS of the two arms were comparable in patients with negative PD-L1 expression, or patients aged ≥ 65 years old. ConclusionsPD-1 inhibitor plus chemotherapy was associated with significant survival benefits compared to bevacizumab plus chemotherapy in patients with advanced non-squamous NSCLC, which could provide evidence support to guide clinical practice. Nonetheless, the comparative survival outcomes in several subgroups indicated that bevacizumab plus chemotherapy still mattered. PD-1 inhibitor plus chemotherapy was associated with significant survival benefits compared to bevacizumab plus chemotherapy in patients with advanced non-squamous NSCLC, which could provide evidence support to guide clinical practice. Nonetheless, the comparative survival outcomes in several subgroups indicated that bevacizumab plus chemotherapy still mattered.