The following is a summary of “Toripalimab Plus Chemotherapy for Patients With Treatment-Naive Advanced Non–Small-Cell Lung Cancer: A Multicenter Randomized Phase III Trial (CHOICE-01),” published in the January 2023 issue of Oncology by Wang, et al.

As a first-line therapy for advanced non-small-cell lung cancer (NSCLC), the CHOICE-01 research examined the efficacy and safety of toripalimab combined with chemotherapy.

Toripalimab 240 mg (n = 309) or a placebo (n = 156) was given once every three weeks in combination with chemotherapy for 4-6 cycles to patients randomly assigned 2:1 (N = 465) with advanced NSCLC who had not received treatment and had no EGFR/ALK mutations. Toripalimab or the placebo was then continued as needed along with standard care. Programmed death ligand-1 expression levels, histology, and smoking status were stratification variables. Progression-free survival (PFS) according to RECIST v1.1 was the main measure of success. Overall safety and survival were secondary endpoints.

When PFS was finally analyzed, it was shown that the toripalimab arm had significantly longer PFS than the placebo arm (median PFS, 8.4 vs. 5.6 months, hazard ratio = 0.49; 95% CI, 0.39 to 0.61; two-sided P< .0001). The toripalimab arm had a substantially longer OS than the placebo arm at the interim OS analysis (median OS not reached vs. 17.1 months, hazard ratio = 0.69; 95% CI, 0.53 to 0.92; two-sided P =.0099). In both arms, the frequency of grade 3 negative events was comparable. Regardless of programmed death ligand-1 status, treatment outcomes were comparable. Patients with a high tumor mutational burden had a significantly higher PFS in the toripalimab arm, according to genomic analysis employing whole-exome sequencing from 394 accessible tumor samples (median PFS 13.1 vs. 5.5 months, interaction P =.026). Importantly, patients receiving toripalimab had significantly better PFS and OS than those with unfavorable mutations in the focal adhesion-PI3K-Akt signaling pathway (interaction P values≤ .001).

In patients with advanced NSCLC who had not received treatment, toripalimab with chemotherapy dramatically increased PFS and OS while having a manageable safety profile. Analysis of subgroups revealed that the nonsquamous subpopulation was primarily responsible for the OS advantage.