LBA93 EXTENTORCH: A randomized, phase III trial of toripalimab versus placebo, in combination with chemotherapy as a first-line therapy for patients with extensive stage small cell lung cancer (ES-SCLC)

Combinations of immunotherapy with chemotherapy as a first-line treatment for ES-SCLC have generated mixed results. The EXTENTORCH trial assessed toripalimab in combination with chemotherapy as a first-line treatment for patients with ES-SCLC (NCT04012606). Patients with histologically or cytologically confirmed ES-SCLC, stratified by gender and baseline ECOG PS (0 vs. 1) were randomized in a 1:1 ratio to receive 240 mg toripalimab or placebo plus etoposide and cisplatin/carboplatin Q3W for 4-6 cycles, followed by single-agent toripalimab or placebo until progressive disease, intolerable toxicity or up to 2-year treatment. The primary endpoints were PFS as assessed by the investigator per RECIST v1.1 and OS. Tumor mutational burden (TMB) and genomic alterations were assessed by whole-exome sequencing (WES) of tumor tissues. From Sep 2019 to May 2021, 442 patients were enrolled from 48 participating sites in China. 223 and 219 patients were randomized to the toripalimab and the placebo arms, respectively. At data cut off (28 Feb 2022), median follow-up was 11.8 months, a significant improvement in PFS was observed for toripalimab over placebo (5.8 vs. 5.6 months, HR = 0.667 [95% CI: 0.539-0.824], P = 0.0002). Despite 59.4% of patients in the placebo arm received ≥3 additional lines of therapy and 25.6% received a PD-(L)1 inhibitor after the study treatments, OS was significantly improved in the toripalimab arm (14.6 vs. 13.3 months, HR = 0.798 [95% CI: 0.648-0.982], P = 0.0327) at the final OS analysis at data cut off (20 Apr 2023). WES results from 300 patients showed that improvements in PFS and OS were similar irrespective of TMB status. Genomic alterations in integrin-mediated focal adhesion complex were associated with poor prognosis for both PFS and OS in the toripalimab arm. Toripalimab plus chemotherapy had a manageable safety profile, with no new safety signals observed. The addition of toripalimab to chemotherapy provided significant improvements in PFS and OS for patients with ES-SCLC with an acceptable safety profile.