Comparison of efficacy and safety between PD-1 inhibitors and PD- L1 inhibitors plus platinum-etoposide as first-line treatment for extensive-stage small-cell lung cancer: a multicenter, real-world analysis

Background: Immunotherapy in combination with platinum-etoposide (EP) chemotherapy has been approved as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, real-world (RW) data regarding the use of immune checkpoint inhibitors (ICIs) in ES-SCLC are lacking. We aimed to assess the differences between programmed death protein 1 (PD-1) inhibitors and programmed death ligand 1 (PD-L1) inhibitors plus EP chemotherapy as first-line treatment for ES SCLC. Methods: We conducted a real-world, multicenter, retrospective cohort, controlled study to compare the prognosis, efficacy, and safety of PD-1 and PD-L1 inhibitors along with chemotherapy for patients with ES-SCLC. Each patient received up to six cycles of etoposide, carboplatin, or cisplatin combined with ICIs drugs, including PD-1 and PD-L1 inhibitors. The primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were investigator-assessed objective response rate (ORR), disease control rate (DCR), and duration of response (DOR)according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results: Between January 2017 and December 2021, 194 patients with ES-SCLC from three clinical centers in a PLA general hospital were included in our study, including 93 patients in the PD-1 group and 101 patients in the PD-L1 group. At the time of data cutoff, progression-free survival in the PD-1 group (median PFS, 6.8months; 95%CI, 5.3-8.1) was similar to the PD-L1 group (median PFS, 6.4months; 95%CI, 5.5-7.5); the stratified hazard ratio for PFS was 1.12 (95%CI, 0.83-1.53; P=0.452). The median OS was similar in the PD-1 and PD-L1 group (15.8m vs 17.7m, P = 0.566); the hazard ratio was 0.90 (95% CI, 0.62-1.30, P=0.566). The two groups had comparable investigator-assessed confirmed objective response rates (ORR) (76.3% vs 76.2%) and median duration of response (DOR) (6.2m vs 6.1m). Adverse effects (AEs) related discontinuation occurred in 4(4.3%) patients in the PD-1 group and 2(2.0%) patients in the PD-L1 group. Deaths due to AEs of any cause occurred in 2(2.2%) patients in the PD-1 inhibitor group and 1(1.0%) patient in the PD-L1 inhibitor group, separately. Conclusions: Our research revealed that no significant differences in efficacy or prognosis were observed between PD-1 inhibitor + EP chemotherapy and PD-L1 inhibitor + EP chemotherapy. The two groups seemed to have comparable safety profiles, but the number of discontinuation or death events is too few to draw a firm conclusion.