KEY TAKEAWAYS
- A phase 3 trial CHOICE-01 study aimed to evaluate the PFS of advanced NSCLC patients treated with toripalimab in combination with chemotherapy.
- 465 patients with advanced NSCLC were randomly assigned to receive either toripalimab 240 mg or a placebo in combination with chemotherapy for 4-6 cycles.
- The trial found that toripalimab, in combination with chemotherapy, significantly improved both PFS and OS compared to chemotherapy alone.
- The trial also found that patients with high TMB of at least 10 mutations per million base pairs exhibited notably improved PFS in the toripalimab treatment group.
- The administration of toripalimab in combination with chemotherapy as the primary treatment option for patients with advanced NSCLC who lack EGFR/ALK
The administration of Toripalimab, an anti-PD-1 agent, in conjunction with chemotherapy, has demonstrated noteworthy enhancements in both progression-free survival (PFS) and overall survival (OS) in the primary treatment of advanced non-small cell lung cancer (NSCLC), irrespective of the tumor’s PD-L1 expression. A WES analysis was conducted to identify potential biomarkers correlating with survival outcomes. A total of 465 patients who had advanced non-small cell lung cancer, had not received any prior treatment, and did not have EGFR/ALK mutations were subjected to randomization in a 2:1 ratio. The patients were then administered either toripalimab 240 mg (n = 309) or placebo (n = 156) in combination with chemotherapy for 4-6 cycles. Following this, the patients were given the maintenance of toripalimab or placebo along with standard care until they experienced disease progression, intolerable toxicity, or completed 2 years of treatment. The stratification factors encompassed PD-L1 expression status, histology, and smoking status. The principal objective was progression-free survival as determined by the investigator according to the Response Evaluation Criteria in Solid Tumors version 1.1.
The secondary endpoints comprised progression-free survival (PFS) evaluated by a blinded independent review committee (BIRC), overall survival (OS), and safety. At the predetermined final progression-free survival (PFS) analysis, conducted on October 31, 2021, a notable enhancement in PFS, as evaluated by the investigator, was detected in the toripalimab group compared to the placebo group. The hazard ratio (HR) was 0.49 (95% CI: 0.39-0.61), with a two-sided P< 0.0001. The median PFS was 8.4 months in the toripalimab group and 5.6 months in the placebo group. The one-year progression-free survival rates were 36.7% compared to 17.2%. The post-progression survival (PFS) evaluated by the Beijing Immunooncology Research Group (BIRC) exhibited a statistically significant increase in the group treated with toripalimab. Enhancements in progression-free survival (PFS) were noted in important subcategories, encompassing histological and PD-L1 expression factors. Upon conducting an interim analysis of the overall survival (OS), it was observed that the arm administered with toripalimab exhibited a significantly longer OS than the placebo arm. The hazard ratio (HR) was calculated to be 0.69 with a 95% CI of 0.52-0.92 and a two-sided P=0.0099.
The median OS for the toripalimab arm was not reached, whereas for the placebo arm, it was 17.1 months. The frequency of Grade ≥3 adverse events (AEs) was comparable between both groups, with a percentage of 78.6% in one arm and 82.1% in the other. Adverse events (AEs) resulting in discontinuation of toripalimab/placebo were observed at a higher rate in the toripalimab group (14.3%) compared to the placebo group (3.2%). Fatal AEs were also more frequent in the toripalimab arm (5.5%) than in the placebo arm (2.6%). The Whole Exome Sequencing (WES) findings of 394 patients indicate that individuals with high tumor mutational burden (TMB) of at least 10 mutations per million base pairs exhibit notably improved progression-free survival (PFS) in the toripalimab treatment group compared to the placebo group (with median PFS of 13.1 months versus 5.5 months, respectively). This observation is statistically significant, as evidenced by an interaction of P=0.026. Furthermore, individuals exhibiting mutations in the FAK-PI3K-Akt pathway or IL-7 signaling pathways demonstrated notably improved progression-free survival (PFS) and overall survival (OS) upon receiving the toripalimab chemotherapy combination (interaction P values ≤ 0.01). Incorporating toripalimab in the chemotherapy regimen for patients with advanced non-small cell lung cancer resulted in improved progression-free survival and overall survival rates compared to chemotherapy alone while maintaining a tolerable safety profile. The findings substantiate the administration of toripalimab in conjunction with chemotherapy as the primary treatment option for patients with advanced non-small cell lung cancer who lack EGFR/ALK mutations.
Source:https://meetings.asco.org/abstracts-presentations/208949
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03856411
Jie Wang, Zhijie Wang, Lin Wu, Baolan Li, Ying Cheng, Xiaoling Li, Xicheng Wang, Liang Han, Xiaohong Wu, Yun Fan, Yan Yu, Dongqing Lv, Jianhua Shi, Jianjin Huang, Shaozhang Zhou, Baohui Han, Guogui Sun, Qisen Guo, Youxin Ji, Xiaoli Zhu/Final progression-free survival, interim overall survival, and biomarker analyses of CHOICE-01: A phase 3 study of toripalimab versus placebo in combination with first-line chemotherapy for advanced NSCLC without EGFR/ALK mutations/J Clin Oncol 40, 2022 (suppl 16; abstr 9028) DOI10.1200/JCO.2022.40.16_suppl.9028
