In a Chinese phase III trial (EXTENTORCH) reported in JAMA Oncology, Cheng et al reported that the addition of the immunoglobulin G4 PD-1–blocking antibody toripalimab to first-line chemotherapy with etoposide plus cisplatin or carboplatin (EP) improved progression-free survival among patients with extensive-stage small cell lung cancer.
Study Details
In the multicenter double-blind trial, 442 eligible patients were randomly assigned between September 2019 and May 2021 to receive toripalimab at 240 mg (n = 223) or placebo (n = 229) plus EP every 3 weeks for up to four to six cycles, followed by maintenance toripalimab or placebo until disease progression, intolerable toxicity, or up to 2 years of treatment. The primary endpoint was investigator-assessed progression-free survival.
Key Findings
Median follow-up was 13.7 (range = 0.0–42.7 month). Median progression-free survival was 5.8 months (95% confidence interval [CI] =5.6–6.8 months) in the toripalimab group vs 5.6 months (95% CI= 5.5–5.7 months) in the control group (hazard ratio [HR] = 0.67, 95% CI = 0.54–0.82, P < .001). Rates at 6 and 12 months were 47.1% vs 36.3% and 18.1% vs 4.9%.
Median overall survival was 14.6 months (95% CI = 12.9–16.6 months) in the toripalimab group vs 13.3 months (95% CI = 11.8–14.4 months) in the control group (HR = 0.80, 95% CI = 0.65–0.98, P = .03). Rates at 12 and 24 months were 63.1% vs 54.9% and 25.9% vs 19.5%.
Whole-exome sequencing data from 300 patients indicated that low intratumor heterogeneity, HLA-A11+ HLA-B62−haplotype, wild-type KMT2D and COL4A4, and sequence variations in CTNNA2 or SCN4A correlated with favorable progression-free and overall survival in the toripalimab group.
Grade ≥ 3 adverse events occurred in 89.6% of the toripalimab group and 89.4% of the control group; the most common in both groups were decreased neutrophils (74.3% vs 75.0%), decreased white blood cell counts (38.7% vs 44.9%), and anemia (40.6% vs 34.7%). Serious adverse events occurred in 50% vs 37.5% of patients. Adverse events led to treatment discontinuation in 12.6% vs 7.9%. Fatal adverse events occurred in 12 patients (5.4%) in the toripalimab group vs 7 patients (3.3%) in the control group.
The investigators concluded; “In this phase 3 randomized clinical trial, adding toripalimab to first-line chemotherapy demonstrated significant improvements in [progression-free and overall survival] for patients with [extensive-stage small cell lung cancer].The treatment exhibited an acceptable safety profile, supporting this combination regimen as a new treatment option for patients with [extensive-stage small cell lung cancer].”
Ying Cheng, MD, of the Department of Oncology, Jilin Cancer Hospital, Changchun, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Shanghai Junshi Biosciences Co Ltd. For full disclosures of all study authors, visit JAMANetwork.com.
