Toripalimab Plus Chemotherapy in Advanced Lung Cancer: CHOICE-01 Trial

The efficacy and safety of toripalimab in combination with chemotherapy as a first-line treatment for advanced non-small-cell lung cancer (NSCLC) were investigated in the CHOICE-01 study. A total of 465 patients who had not received any prior treatment for advanced non-small cell lung cancer (NSCLC) and did not have EGFR/ALK mutations were subjected to a random assignment in a ratio of 2:1. The patients were administered toripalimab 240 mg (n=309) or placebo (n=156) once every 3 weeks along with chemotherapy for 4-6 cycles. This was followed by maintaining toripalimab or placebo once every 3 weeks, along with standard care. The stratification factors comprised the programmed death ligand-1 expression status, histology, and smoking status. The principal objective was assessing progression-free survival (PFS) as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoints encompassed the patients’ overall survival (OS) and safety. Upon conducting the final progression-free survival (PFS) analysis, it was observed that the toripalimab arm exhibited a significantly longer PFS than the placebo arm (with a median PFS of 8.4 months versus 5.6 months, respectively).

The hazard ratio was calculated to be 0.49 with a 95% confidence interval of 0.39 to 0.61 and a two-sided P < .0001. Upon conducting the interim overall survival analysis, it was observed that the toripalimab arm exhibited a considerably longer OS than the placebo arm. The median OS was not reached in the toripalimab arm, whereas it was 17.1 months in the placebo arm. The hazard ratio was 0.69, and the two-sided P =0.0099, with a 95% confidence interval of 0.53 to 0.92. The frequency of adverse events of grade ≥ 3 was comparable in both groups. The therapeutic outcomes were consistent irrespective of the programmed death ligand-1 status. The examination of genomic data through whole-exome sequencing of 394 tumor samples indicated that patients with elevated tumor mutational burden demonstrated notably improved PFS in the toripalimab treatment group (with a median PFS of 13.1 months compared to 5.5 months in the control group, with an interaction P=.026). Notably, individuals exhibiting mutations in the focal adhesion-PI3K-Akt signaling pathway demonstrated considerably improved PFS and OS in the toripalimab group (interaction P values ≤ .001).

The combination of Toripalimab and chemotherapy has significantly improved PFS and overall survival OS among patients with advanced non-small cell lung cancer (NSCLC) who have not received prior treatment. Additionally, this treatment approach has been found to have a manageable safety profile. The analysis of subgroups indicated that the nonsquamous subpopulation primarily influenced the overall survival benefit.

Source:https://pubmed.ncbi.nlm.nih.gov/36206498/

Clinical Trail:https://clinicaltrials.gov/ct2/show/NCT03856411

Wang Z, Wu L, Li B, Cheng Y, Li X, Wang X, Han L, Wu X, Fan Y, Yu Y, Lv D, Shi J, Huang J, Zhou S, Han B, Sun G, Guo Q, Ji Y, Zhu X, Hu S, Zhang W, Wang Q, Jia Y, Wang Z, Song Y, Wu J, Shi M, Li X, Han Z, Liu Y, Yu Z, Liu AW, Wang X, Zhou C, Zhong D, Miao L, Zhang Z, Zhao H, Yang J, Wang D, Wang Y, Li Q, Zhang X, Ji M, Yang Z, Cui J, Gao B, Wang B, Liu H, Nie L, He M, Jin S, Gu W, Shu Y, Zhou T, Feng J, Yang X, Huang C, Zhu B, Yao Y, Tang X, Yu J, Maher E, Feng H, Yao S, Keegan P, Wang J. Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non-Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01). J Clin Oncol. 2023 Jan 20;41(3):651-663. doi: 10.1200/JCO.22.00727. Epub 2022 Oct 7. PMID: 36206498; PMCID: PMC9870236.