Immunotherapy as first-line treatment for patients with advanced esophageal squamous cell carcinomas

March 2022 Cancer trials Nalinee Pathak

The addition of toripalimab to chemotherapy significantly improved progression-free survival (PFS) and overall survival (OS) in untreated patients with advanced esophageal squamous cell carcinomas (ESCC). The phase III JUPITER-6 trial findings published in the journal Cancer cell provide solid evidence for using immune checkpoint inhibitors (ICBs) as first-line treatment for ESCC patients.

The current standard of care for ESCC patients is platinum-based chemotherapy. In a phase 1b trial, toriplaimab, a humanised monoclonal antibody against PD-1, has shown high efficacy when combined with paclitaxel plus cisplatin (TP). The combination was evaluated in phase III, JUPITER-6 trial for its effectiveness for advanced or metastatic ESCC.

JUPITER-6 study

The double-blind,phase-III, JUPITER-6 study enrolled 514 ESCC patients. They were randomly (1:1) administered toripalimab (240 mg) or placebo in combination with TP Q3W up to 6 cycles, followed by toripalimab or placebo maintenance. The study’s primary endpoints were PFS and OS.

Results

At a median follow up of 7.4 and 7.3 months in the two treatment arms, the OS was significantly improved from 11.0  (Placebo arm) to 17.0 months with toripalimab treatment (HR=0.58 [95% CI: 0.43-0.78], P=0.00037). Similar improvement was also observed in PFS for toripalimab over placebo (HR=0.58 [95% CI: 0.46-0.74], P<0.00001). Grade ≥3 adverse events (AEs) and fatal AEs were similar in both the treatment arms, however, AEs related discontinuation (11.7% vs 6.2%), immune-related AEs (37.0% vs 26.5%) and Grade ≥3 irAEs (6.6% vs. 1.6%) were more frequent in toriplaimab arm.

Conclusion

The findings of the JUPITER-3 trial support the use of toripolimab plus chemotherapy as first-line therapy for advanced or metastatic ESCC.

Reference

Wang, Z.-X. et al. Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-centre phase 3 trial. Cancer Cell 40, 277-288.e3 (2022).

 

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