Efficacy and safety of anti-PD-1 inhibitor versus anti-PD-L1 inhibitor in first-line treatment of extensive-stage small cell lung cancer: a multicenter retrospective study

Abstract

Background: Immunotherapy targeting PD-1/PD-L1 has revolutionized the treatment of extensive-stage small cell lung cancer (ES-SCLC). However, clinical trials suggest differential efficacy of anti-PD-1 agents and anti-PD-L1 agents in first-line treatment of ES-SCLC. This retrospective multicenter study aimed to compare the efficacy and safety of anti-PD-1 agents versus anti-PD-L1 agents in first-line treatment of ES-SCLC in real-world practice.

Methods: Patients with pathologically or cytologically confirmed ES-SCLC treated with platinum plus etoposide combined with anti-PD-1 or PD-L1 agents as first-line treatment in different centers of PLA General Hospital between January 2017 and October 2021 were included for this study. Survival outcomes and safety were compared between patients receiving anti-PD-1 and PD-L1 agents.

Results: Of the total 154 included patients, 68 received anti-PD-1 agents plus chemotherapy (PD-1 group), and 86 received anti-PD-L1 agents plus chemotherapy (PD-L1 group). Progression-free survival (PFS) and overall survival (OS) in the entire cohort were 7.6 months (95% confidence interval [CI]: 6.5-8.2 months) and 17.4 months (95% CI: 15.3-19.3 months), respectively. Median PFS and OS were comparable between the PD-1 group and PD-L1 group (PFS: 7.6 months vs. 8.3 months, HR = 1.13, 95% CI: 0.79-1.62, p = 0.415; OS: 26.9 months vs. 25.6 months, HR = 0.96, 95% CI: 0.63-1.47, p = 0.859. The objective response rate and disease control rate were comparable between the two groups: 79.4% vs. 79.1% and 92.6% vs. 94.2%, respectively. The 6-month, 12-month, and 18-month PFS and OS rates were slightly higher in the PD-L1 group than in the PD-1 group, while the 24-month PFS rate was slightly higher in the PD-1 group than in the PD-L1 group. Stratified analysis showed that locoregional thoracic radiotherapy and normal lactate dehydrogenase level were independent predictors of better OS in ES-SCLC patients treated with first-line chemotherapy plus ICI. Adverse events were not significantly different between the two groups.

Conclusions: Anti-PD-1 agents and anti-PD-L1 agents combined with chemotherapy as first-line treatment for ES-SCLC are comparably effective and well tolerated.

Keywords: Anti-PD-1/PD-L1; Immunotherapy; Lactate dehydrogenase; Locoregional thoracic radiotherapy; Small cell lung cancer.

Fig. 1

Workflow of this study

Fig. 2

Kaplan-Meier curve of PFS and OS. A: PFS between PD-1 group and PD-L1 group; B: OS between PD-1 group and PD-L1 group

Fig. 3

Predictors of PFS and OS in whole patients. A: Patients without liver metastases had longer PFS; B: Patients received locoregional thoracic radiotherapy had longer PFS; C: Patients with normal LDH had longer OS; D: Patients received locoregional thoracic radiotherapy had longer OS

Fig. 4

Stratified analysis of PFS in patients of PD-1 group or PD-L1 group. A: In PD-1 group, locoregional thoracic radiotherapy was related with better PFS; B-C: In PD-L1 group, liver metastases and locoregional thoracic radiotherapy were related with better PFS