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

March 2022 Cancer trials Nalinee Pandey
TRACHEA (windpipe) and ESOPHAGUS in Cross Section, 3X. The trachea (larger circular structure) shows an inner lining composed of ciliated cells, and a C-shaped supporting tracheal cartilage composed of hyaline cartilage. The esophagus is the smaller, flatter tube located posterior to the trachea, the darker inner lining is stratified squamous epithelium. This image also shows part of the lobes of the thyroid gland.

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.


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.


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


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).