Esophageal cancer is among the top most common cancers worldwide and is the sixth leading cause of cancer-related mortality worldwide.1 The primary histologic types of esophageal cancer are squamous-cell carcinoma and adenocarcinoma.1 Males have an increased risk of developing both types of esophageal cancer, and it is common for patients to be diagnosed at an advanced stage, which leads to poor prognosis.1 Esophageal squamous-cell carcinoma (ESCC) has a higher incidence in Eastern Asia and Africa, with China accounting for >50% of global cases.2 Neoadjuvant chemotherapy and chemoradiotherapy have improved 5-year survival rates over the past few decades, and with the introduction of immunotherapy there is promising evidence that it may improve survival rates.2 Currently, pembrolizumab and nivolumab, both PD-1 inhibitors, have approval as second-line treatment for patients with advanced ESCC.2 Toripalimab is also an anti–PD-1 antibody that is being studied along with neoadjuvant chemotherapy in patients with advanced ESCC.2 At the European Society for Medical Oncology Congress 2021, Xu and colleagues presented data from the JUPITER-06 clinical trial that investigated toripalimab versus placebo in combination with first-line chemotherapy as frontline treatment for advanced or metastatic ESCC. This randomized, double-blind, phase 3 trial included 514 patients divided into 2 treatment arms. Treatment arm 1 received 240 mg of toripalimab in combination with paclitaxel plus cisplatin every 3 weeks for up to 6 treatment cycles followed by toripalimab maintenance. Arm 2 received 240 mg of placebo along with paclitaxel plus cisplatin every 3 weeks for up to 6 treatment cycles followed by placebo maintenance. The study’s primary end points were progression-free survival (PFS) and overall survival (OS).
Analysis revealed that arm 1 had a median OS of 17.0 months and arm 2 had a median OS of 11.0 months. The 1-year OS rates were 66.0% for arm 1 and 43.7% for arm 2. PFS was also significantly improved in arm 1. When subgroups were analyzed, including all PD-L1 expression subgroups, OS and PFS benefits with toripalimab held. Evaluation of adverse events found 73.3% of arm 1 patients and 70.0% of arm 2 patients had grade ≥3 adverse events. Fatal events associated with treatment occurred in 8.2% of arm 1 patients and 8.2% of arm 2 patients. Toripalimab use led to 11.7% of patients discontinuing treatment compared with 6.2% of patients receiving placebo who discontinued treatment. Immune-related adverse events led to 37.0% of patients receiving toripalimab to discontinue treatment compared with 26.5% of patients receiving placebo. Immune-related grade ≥3 adverse events occurred in 6.6% of patients in arm 1 and 1.6% of patients in arm 2.
Toripalimab combined with chemotherapy as first-line treatment in patients with advanced or metastatic ESCC conveyed significant PFS and OS benefits compared with patients receiving placebo plus chemotherapy.
Xu R, 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. Ann Oncol. 2021;32(suppl_5):S1040-S1075.
- Then EO, Lopez M, Saleem S, et al. Esophageal cancer: an updated Surveillance Epidemiology and End Results database analysis. World J Oncol. 2020;11:55-64.
- Xing W, Zhao L, Fu X, et al. A phase II, single-centre trial of neoadjuvant toripalimab plus chemotherapy in locally advanced esophageal squamous cell carcinoma. J Thorac Dis. 2020;12:6861-6867.