Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma
Mené sur 30 patients atteints d’un carcinome épidermoïde œsophagien de stade localement avancé ou d’un adénocarcinome de l’estomac ou de la jonction œsogastrique, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse objective, de la durée de la réponse, du taux de contrôle de la maladie et de la survie sans progression, et la toxicité d’un traitement de première ligne combinant tislélizumab (un anticorps anti-PD-1) et chimiothérapie
Purpose: This phase 2 study (NCT03469557) assessed safety/tolerability and antitumor activity of first line tislelizumab, a monoclonal antibody against PD-1, plus chemotherapy in patients with locally advanced/metastatic esophageal squamous cell carcinoma (ESCC) or gastric cancer/gastroesophageal junction (G/GEJ) adenocarcinoma. Experimental Design: Patients with ESCC received tislelizumab (200mg IV every 3 weeks [Q3W]) plus cisplatin (80mg/m² IV Q3W for ?6 cycles) and fluorouracil (800mg/m²/d, Days 1-5 IV Q3W for ?6 cycles); patients with G/GEJ adenocarcinoma received tislelizumab (200mg IV Q3W) plus oxaliplatin (130mg/m² IV Q3W for up to six cycles) and oral capecitabine (1000mg/m² twice daily, Days 1-14 Q3W). The safety/tolerability profile of combination therapy was the primary endpoint; secondary endpoints included objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and progression-free survival per RECIST v1.1. Exploratory endpoints included overall survival and potential predictive biomarkers. Results:As of March 31, 2019, 30 patients (n=15 per cohort) were enrolled. Most common adverse events considered related to tislelizumab and/or chemotherapy were anemia (n=18), decreased appetite (n=17), nausea (n=16), and asthenia (n=15). One patient experienced fatal hepatic dysfunction, confounded by progressive disease and underlying hepatitis, attributed to treatment by the investigator. Confirmed ORRs and DCRs were 46.7% and 80%, respectively, for both ESCC and G/GEJ adenocarcinoma. In ESCC, median DoR was 12.8 months (95% CI: 3.5, 12.8); DoR was not yet mature for the G/GEJ cohort. Conclusions: Tislelizumab plus chemotherapy demonstrated durable responses with manageable tolerability in patients with advanced ESCC or G/GEJ adenocarcinoma.