Toripalimab Plus Chemotherapy as First-Line Treatment For Metastatic Esophageal Squamous Cell Carcinoma

Interim analyses of the phase 3 JUPITER-06 trial demonstrated superior overall survival (OS) and progression-free survival (PFS) with the addition of toripalimab to standard first-line chemotherapy compared with chemotherapy alone in patients with advanced esophageal squamous cell carcinoma (ESCC).

“Toripalimab in combination with paclitaxel and cisplatin has the potential to become a new standard first-line therapy in patients with advanced or metastatic ESCC,” said Ruihua Xu, MD, PhD, of the Sun-Yat Sen University Cancer Center in China, during her presentation at the European Society for Medical Oncology (ESMO) Congress 2021.

Toripalimab is a humanized monoclonal antibody against PD-1 that showed promising efficacy as a first-line treatment for ESCC in combination with paclitaxel plus cisplatin in a phase 1b trial (ClinicalTrials.gov Identifier: NCT02915432).

The randomized, double-blind, placebo-controlled, multicenter, phase 3 JUPITER-06 trial (ClinicalTrials.gov Identifier: NCT03829969) enrolled 514 treatment-naive patients with ESCC. An equal number of patients were randomly assigned to receive either toripalimab in combination with paclitaxel plus cisplatin (toripalimab arm) or placebo in combination with paclitaxel plus cisplatin (placebo arm).

After a median follow-up of approximately 7.3 to 7.4 months, the research team observed a significant improvement in the median OS in the toripalimab arm (17 months) compared with the placebo arm (11 months; stratified hazard ratio [HR] for death, 0.58; 95% CI, 0.43-0.78, P =.00036).

The 1-year OS rate in the toripalimab arm was 66.0% (95% CI, 57.5-73.2) compared with 43.7% (95% CI, 34.4-52.6) in the placebo arm. The median PFS was 5.7 months for the toripalimab arm compared with 5.5 months for the placebo arm (HR, 0.58; 95% CI, 0.46-0.74; P <.00001).

The 1-year PFS rate was 27.8% (95% CI, 20.4-35.8) for the toripalimab arm compared with 6.1% (95% CI, 2.2-12.6) for the placebo arm. The stratified HR for disease progression or death was 0.58 (95% CI, 0.46-0.74; P <.00001). The OS and PFS benefits were observed across key subgroups, including all PD-L1 expression subgroups.

Among patients with PD-L1 expression with a combined positive score (CPS) greater than or equal to 1, the median OS in the toripalimab arm was 15.2 months compared with 10.9 months in the placebo arm (HR, 0.61; 95% CI, 0.44-0.87). In patients with CPS less than 1, the median OS was not reached compared with 11.6 months in the placebo arm (HR, 0.61; 95% CI, 0.30-1.25).

Grade 3 or worse adverse events (AEs) occurred at nearly similar rates in the toripalimab arm (73.2%) compared with the placebo arm (70.0%). The incidence of serious AEs was also similar (8.2% in each arm).

Immune-related AEs (irAEs) were more frequently observed in the toripalimab arm (37.0%) compared with the placebo arm (26.5%). Grade 3 or higher irAEs occurred in 6.6% of the patients in the toripalimab arm compared with 1.6% in the placebo arm.  AEs led to treatment discontinuation in 11.7% of the patients in the toripalimab arm and 6.2% of the patients in the placebo arm.  There were no new safety signals identified with the addition of toripalimab to chemotherapy.

Overall, “these results support the use of toripalimab with [paclitaxel plus cisplatin] chemotherapy as a new first-line treatment for advanced or metastatic ESCC,” Dr Xu said.

Disclosure: This research was supported by Shanghai Junshi Biosciences and Coherus Biosciences. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Xu RH, Wang F, Cui C, et al. JUPITER-06: A randomized, double-blind, phase III study of toripalimab versus placebo in combination with first-line chemotherapy for treatment naive advanced or metastatic esophageal squamous cell carcinoma (ESCC). Presented at: European Society for Medical Oncology (ESMO) Congress 2021; September 16-21, 2021. Abstract 1373MO.

This article originally appeared on Cancer Therapy Advisor