Tislelizumab–chemotherapy combo poised as new first-line option for advanced gastric cancer

Adding the anti-PD-1 monoclonal antibody tislelizumab to chemotherapy in the first-line treatment of PD-1-positive advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) appears to produce significant and clinically meaningful improvements in survival outcomes while having an acceptable safety profile, according to interim data from the phase III RATIONALE 305 trial.

Compared with placebo plus chemotherapy, tislelizumab plus chemotherapy prolonged overall survival (OS; median, 17.2 vs 12.6 months; hazard ratio [HR], 0.74, 95 percent confidence interval [CI], 0.59–0.94; p=0.0056) and progression-free survival (PFS; median, 7.2 vs 5.9 months; HR, 0.67, 95 percent CI, 0.55–0.83). [J Clin Oncol 2023;41(suppl 4; abstr 286)]

Tislelizumab plus chemotherapy was also associated with a higher objective response rate (ORR; 50.4 percent vs 43.0 percent) and more durable response (median duration of response [DoR], 9.0 vs 7.1 months).

“Patients treated with tislelizumab plus chemotherapy reported better health-related quality of life than patients treated with placebo plus chemotherapy, as indicated by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) global health status and physical functioning scores, as well as the QLQ-ST022 index score,” first author Dr Markus Moehler of Johannes Gutenberg-University Clinic, Mainz, Germany, reported at the ASCO Gastrointestinal Cancer Symposium.

No new safety signals were observed in either treatment arm, Moehler added.

Treatment emergent adverse events (TEAEs) leading to discontinuation of any treatment occurred more frequently with tislelizumab plus chemotherapy than with placebo plus chemotherapy (22.4 percent vs 12.1 percent). However, the two treatment arms did not differ in terms of the frequency of grade ≥3 TEAEs (64.7 percent vs 62.9 percent), serious TEAEs (42.3 percent vs 36.8 percent), and TEAEs leading to death (8.8 percent vs 7.7 percent).

These data suggest the feasibility of the tislelizumab­–chemotherapy combination as a new first-line treatment option for the GC/GEJC population, according to Moehler.

The addition of PD-1 antibodies to chemotherapy has been shown to improve survival, and tislelizumab is not new. Moehler cited two other trials, RATIONALE 301 and 306, in which tislelizumab was associated with positive survival outcomes for other diseases—unresectable hepatocellular carcinoma and advanced esophageal squamous cell carcinoma, respectively.

RATIONALE 305 included 546 patients with PD-L1-positive GC/GEJC, enrolled from 13 counties/regions (73.8 percent in Asia and 26.2 percent in Europe/ North America). Of these patients, 274 (median age 61 years, 70.4 percent male) were randomly assigned to receive tislelizumab plus chemotherapy and 272 (median age 62 years, 73.9 percent male) to receive placebo plus chemotherapy. None of the patients had HER2-positive disease.

Tislelizumab was given intravenously at 200 mg every 3 weeks. The chemotherapy regimen used, either oxaliplatin (130 mg/m² IV Q3W) and oral capecitabine (1,000 mg/m² BID, days 1-14 Q3W) or cisplatin (80 mg/m² IV Q3W) and 5-fluorouracil (800 mg/m²/day IV, days 1-5 Q3W), was left at the discretion of the investigators.