As reported in the Journal of Clinical Oncology by Wang et al, a Chinese phase III trial (CHOICE-01) has shown prolonged progression-free survival with the addition of the anti–PD-1 monoclonal antibody toripalimab to platinum-based chemotherapy in the first-line treatment of patients with advanced non–small cell lung cancer (NSCLC) without EGFR/ALK alterations.

Study Details

The multicenter, double-blind trial included 465 patients. They were randomly assigned 2:1 between April 2019 and August 2020 to receive toripalimab at 240 mg (n = 309) or placebo (n = 156) every 3 weeks in combination with chemotherapy for four to six cycles, followed by maintenance toripalimab or placebo every 3 weeks. Chemotherapy consisted of nab-paclitaxel plus carboplatin among patients with squamous disease (147 in the toripalimab group, 73 in the placebo group) and pemetrexed plus cisplatin or carboplatin in those with nonsquamous disease (162 and 83, respectively).

The primary endpoint was investigator-assessed progression-free survival.

Progression-Free Survival  

At final analysis (data cutoff in October 2021), median progression-free survival was 8.4 months (95% confidence interval [CI] = 7.7–9.6 months) in the toripalimab group vs 5.6 months (95% CI = 5.5–6.8 months) in the placebo group (hazard ratio [HR] = 0.49, 95% CI = 0.39–0.61, P < .0001). Rates at 1 year were 36.7% vs 17.2%.

By the data cutoff date (October 2021), 13% vs 65% of patients had received subsequent anti–PD-1/PD-L1 treatment. At the second interim analysis of overall survival (median follow-up = 16.2 months), performed at the time of final progression-free survival analysis, median overall survival was not reached in the toripalimab group (95% CI = 21.7 months to not evaluable) vs 17.1 months (95% CI = 14.4–22.2 months) in the placebo group (HR = 0.69, 95% CI = 0.53–0.92, P = .0099). Rates at 1 and 2 years were 74.0% vs 72.8% and 51.2% vs 33.9%, respectively.

Outcomes did not differ according to PD-L1 status. According to the investigators, whole-exome sequencing analysis data from 394 patients indicated significantly better progression-free survival among patients in the toripalimab group with vs without high tumor mutational burden, and improved progression-free and overall survival among those with vs without mutations in the focal adhesion-PI3K-Akt signaling pathway.

Adverse Events

Grade ≥ 3 adverse events occurred in 79% of patients in the toripalimab group vs 82% of the placebo group, most commonly hematologic adverse events including neutropenia (56% vs 54%) and leukopenia (36% vs 42%). Serious adverse events occurred in 45% vs 35% of patients.

Adverse events led to discontinuation of toripalimab vs placebo in 14% vs 3%. Immune-related adverse events occurred in 49% vs 21% and were grade ≥ 3 in 16% vs 2%. Fatal adverse events occurred in 5.5% vs 2.6% of patients.  

The investigators concluded, “Toripalimab plus chemotherapy significantly improves progression-free survival and overall survival in patients with treatment-naive advanced NSCLC while having a manageable safety profile.”

Jie Wang, MD, of the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Shanghai Junshi Biosciences, National Key Research and Development Project, National Natural Sciences Foundation of China, and others. For full disclosures of the study authors, visit ascopubs.org.