Adding the PD-1 inhibitor toripalimab to chemotherapy significantly improved survival compared with chemotherapy alone in patients with advanced non–small cell lung cancer (NSCLC) without EGFR/ALK mutations, according to research presented during the 2022 ASCO Monthly Plenary Series.¹

At the prespecified final progression-free survival analysis, the 1-year progression-free survival rates more than doubled with the combination of toripalimab and histology-specific doublet chemotherapy vs doublet chemotherapy alone (36.7% vs 17.2%). Interim overall survival analysis of the CHOICE-01 study also showed significantly longer overall survival with the triplet regimen compared with the placebo arm.

Jie Wang, MD, PhD

“These results support the use of toripalimab with chemotherapy as first-line therapy for patients with advanced NSCLC without EGFR/ALK mutations,” said lead study author Jie Wang, MD, PhD, of the National Cancer Center and Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

For this double-blind, placebo-controlled, multicenter phase III trial, 465 patients with treatment-naive advanced NSCLC without EGFR/ALK mutations were randomly assigned to receive toripalimab at 240 mg (309 patients) or placebo (156 patients) in combination with chemotherapy for four to six cycles. This was followed by maintenance of toripalimab or placebo plus standard care until disease progression, intolerable toxicity, or completion of 2 years of treatment.

Dr. Wang and colleagues stratified patients by PD-L1 expression status, histology, and smoking status. The primary endpoint was progression-free survival by investigator per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included progression-free survival by a blinded independent review committee, overall survival, and safety.

Significant Improvements in Outcomes

At the cutoff date of October 31, 2021, data showed a significant improvement in progression-free survival for patients randomly assigned to toripalimab vs placebo. The median progression-free survival was 8.4 months with the triplet regimen vs 5.6 months with chemotherapy alone (hazard ratio [HR] = 0.49; P < .0001). Improvements in progression-free survival were observed across key subgroups, including histology and PD-L1 expression.

Genomic analysis using whole-exome sequencing revealed that patients with high tumor mutational burden (> 10 mutations per million base pairs) had significantly better progression-free survival with toripalimab vs placebo (13.1 vs 5.5 months). “Patients with mutations in the FA-PI3K-Akt pathway or IL-7 signaling pathways also achieved significantly better progression-free survival and overall survival in the toripalimab arm,” added Dr. Wang.

Additionally, interim overall survival analysis showed significantly longer overall survival with toripalimab vs the placebo. Median overall survival has still not been reached with the triplet regimen compared with 17.1 months with chemotherapy alone.

Dr. Wang noted that crossover was allowed, and most patients in the placebo arm crossed over to receive the investigational agent at the time of progressive disease.

Of note, no new safety signals were observed, according to Dr. Wang, and the incidence of grade 3 or greater adverse events was similar between the two arms (78.6% vs 82.1%). Adverse events leading to discontinuation of treatment (14.3% vs 3.2%) and fatal adverse events (5.5% vs 2.6%), however, were more frequent with toripalimab than the placebo. 

DISCLOSURE: Dr. Wang reported no conflicts of interest.

REFERENCE

1. Wang J, Wang, Z, Wu L, et al: Final progression-free survival, interim overall survival, and biomarker analyses of CHOICE-01. 2022 ASCO Monthly Plenary Series. Abstract 362936. Presented March 15, 2022.