EXTENTORCH Trial Results of First-Line Toripalimab Versus Placebo Plus Chemotherapy in Extensive-Stage SCLC

Small cell lung cancer (SCLC) is associated with poor prognosis, with limited treatment options. The randomized, placebo-controlled, phase 3 EXTENTORCH trial (NCT04012606) assessed the clinical efficacy and safety of the anti–PD-1 antibody toripalimab in combination with etoposide plus platinum-based chemotherapy for the first-line treatment of patients with extended-stage SCLC (ES-SCLC); initial results of this study, presented at the 2023 ESMO annual meeting, are summarized here.

The study enrolled patients with histologically or cytologically confirmed ES-SCLC from 48 participating sites in China. Eligible patients were randomized in a 1:1 ratio to receive toripalimab (240 mg) or placebo in combination with chemotherapy consisting of etoposide and cisplatin/carboplatin (every 3 weeks for 4-6 cycles), followed by single-agent toripalimab or placebo until progressive disease, intolerable toxicity, or up to 2 years. The primary end points were progression-free survival (PFS) as assessed by the investigator and overall survival (OS). Assessment of tumor mutational burden (TMB) and genomic alterations was performed by whole-exome sequencing.

A total of 442 patients were enrolled in the EXTENTORCH trial; of these, 223 patients were randomized to the toripalimab arm and 219 patients to the placebo arm. At median follow-up of 11.8 months (data cutoff: February 28, 2022), the toripalimab arm was associated with a significant prolongation of PFS compared to the placebo arm, with a 33% reduction in risk of progression (5.8 vs 5.6 months; hazard ratio [HR], 0.667; P=.0002). At the final OS analysis (data cutoff: April 20, 2023), the PFS benefit in the toripalimab arm translated into a significant improvement in OS (14.6 vs 13.3 months; HR, 0.798; P=.0327); this OS benefit was noted despite the placebo cohort receiving ≥3 additional lines of therapy after the study treatment (59.4%) including PD-L1 inhibitor (25.6%).

Correlative analysis data (n=300) showed that improvements in PFS and OS were independent of TMB status. In the toripalimab cohort, genomic alterations in the integrin-mediated focal adhesion complex were identified as a poor prognostic factor for both PFS and OS.

Data from the safety analysis indicated that the toripalimab-based cohort exhibited a manageable safety profile. Any-grade treatment-emergent adverse events (TEAEs) occurred in 99.5% of the toripalimab + chemotherapy therapy arm compared to 100% of patients in the placebo + chemotherapy arm. Grade ≥3 TEAEs occurred in 89.6% of the toripalimab arm and 89.4% of the placebo arm. There were 7 any-grade TEAEs leading to discontinuation in the toripalimab and placebo arms, respectively.

The authors concluded that the addition of toripalimab to chemotherapy resulted in significant improvements in PFS and OS and was associated with an acceptable safety profile in patients with ES-SCLC.

Source:

Ying L. 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). Abstract presented at: ESMO Annual Meeting, October 20-24, 2023; Madrid, Spain. Abstract LBA93.