Surgery after induced anti-PD-L1 therapy and chemotherapy for stage I‒III small-cell lung cancer: a phase 2 trial (LungMate-005).

Immunochemotherapy has shown promising outcomes in treating small-cell lung cancer. To explore whether surgery after immunochemotherapy benefits patients with stage I‒III small-cell lung cancer, we conducted a phase II trial (NCT04539977). Eligible patients received four cycles of anti-PD-L1 antibody (TQB2450) therapy and chemotherapy, followed by surgery or radiotherapy and one-year maintenance immunotherapy (TQB2450). Forty patients were enrolled between December 2020 and January 2023. Thirty-eight (95.0%) patients had stage III disease. We found that the objective response rate, as the primary endpoint of this study, was 92.5% (95% CI: 83.9%‒100%) in the intention-to-treat population. At a median follow-up of 25.8 months, the median event-free survival (EFS) was 16.2 months. The median overall survival (OS) was not reached. The major pathological response and pathological complete response rate of operative patients (n = 21) were 61.9% and 42.9%, respectively. The 24-month EFS and 24-month OS of operative patients were 61.9% and 85.7%, respectively. All patients with N1 disease (n = 9) underwent surgery, with the 24-month EFS of 66.7% and 24-month OS of 88.9%. The most common TQB2450-specific adverse event was rash of grade 1‒2 (12.5%). We further explored the biomarker of immunochemotherapy and molecular changes during immunochemotherapy through bulk-RNA sequencing and whole-exome sequencing. We demonstrated that PRSS8 was a potential biomarker for poor effectiveness of immunochemotherapy. In conclusion, surgery after neoadjuvant immunochemotherapy is feasible for treating patients with stage I‒III small-cell lung cancer.