Frontline Tislelizumab Plus Chemotherapy for Patients With Gastroesophageal Squamous Cell Carcinoma

Tislelizumab plus chemotherapy improved the overall survival, compared to placebo plus chemotherapy, for patients with advanced or metastatic gastroesophageal squamous cell carcinoma.

Jianming Xu, MD, Chinese PLA General Hospital, Beijing, China, and coauthors wrote, “The options for first-line treatment of advanced [gastroesophageal] squamous cell carcinoma are scarce, and the outcomes remain poor.” For patients in this population who have previously been treated, the anti-PD-1 antibody tislelizumab has shown antitumor activity. The RATIONALE-306 study evaluated tislelizumab plus chemotherapy as a first-line treatment for patients with advanced or metastatic gastroesophageal squamous cell carcinoma.

In this double-blinded, global phase 3 trial, 649 patients with unresectable, locally advanced, recurrent, or metastatic gastroesophageal squamous cell carcinoma were enrolled between December 12, 2018 and November 24, 2020 at centers across Asia, Europe, Oceania, and North America. Patients were randomized on a 1-to-1 basis to receive chemotherapy plus either 200 mg tislelizumab  every 3 weeks on day 1 or placebo. The chemotherapy doublet was chosen by investigator, consisted of a platinum agent (cisplatin or oxaliplatin) and either a fluoropyrimidine (fluorouracil or capecitabine) or paclitaxel. The primary end point was overall survival.

The median follow-up duration was 16.3 months in the tislelizumab arm and 9.8 months in the placebo group. The median overall survival of in the tislelizumab arm was 17.2 months vs 10.6 months in the placebo arm (stratified hazard ratio [HR]: 0.66; 95% confidence interval [CI], 0.54 to 0.80; one-sided P < .0001).

The most common grade 3/4 treatment-related treatment emergent adverse events were decreased neutrophil count, decreased white blood cell count, and anemia. The were a total of 10 deaths on study (6 in the tislelizumab arm; 4 in the placebo arm) that were determined to be treatment-related. In the tislelizumab group, the deaths were due to gastrointestinal and upper gastrointestinal hemorrhage (n = 2), myocarditis, pulmonary tuberculosis, electrolyte imbalance, and respiratory failure). In the placebo group, the deaths were due to pneumonia, septic shock, and unspecified death (n = 2).

Dr Xu et al concluded that “tislelizumab plus chemotherapy as a first-line treatment for advanced or metastatic [gastroesophageal] squamous cell carcinoma provided superior overall survival with a manageable safety profile vs placebo plus chemotherapy.”

Source:

Xu J, Kato K, Raymond E, et al. Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): A global, randomised, placebo-controlled, phase 3 study. Lancet Oncol. Published on April 17, 2023. doi: 10.1016/S1470-2045(23)00108-0