Tislelizumab regimen new first-line option for gastric, gastroesophageal cancer subgroup
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Tislelizumab plus chemotherapy demonstrated statistically significant and clinically meaningful improvements in OS vs. chemotherapy alone among patients with PD-L1-positive, advanced gastric or gastroesophageal junction adenocarcinoma.
The findings, presented at ASCO Gastrointestinal Cancers Symposium, additionally showed first-line treatment with tislelizumab (BGB-A317, BeiGene), a humanized immunoglobulin G4 anti-PD-1 monoclonal antibody, combined with chemotherapy appeared safe, with no new adverse events observed.
Rationale and methods
“Gastric cancer is the fifth most common cancer globally and is more prevalent in Eastern Asia,” Markus Moehler, MD, PhD, professor of gastrointestinal oncology at Johannes-Gutenberg University in Germany, said during a presentation. “Prognosis for patients with advanced unresectable or metastatic gastric cancer or gastroesophageal junction adenocarcinoma treated with standard-of-care chemotherapy remains unsatisfying.”
Previous studies have shown tislelizumab plus chemotherapy conferred durable antitumor activity among this patient population.
The current global, double-blind, phase 3 RATIONALE 305 study compared the combination vs. chemotherapy alone among adults receiving treatment for histologically confirmed advanced gastric cancer or gastroesophageal junction adenocarcinoma.
Moehler presented results of an interim analysis performed in a subset of 546 patients with PD-L1-positive disease.
Researchers randomly assigned patients to either tislelizumab dosed at 200 mg plus 130 mg/m² oxaliplatin every 3 weeks and 1,000 mg/m² capecitabine on days 1 to 14 every 3 weeks (n = 274; median age, 61 years; 70.4% men; 73.7% East Asian) or chemotherapy alone (n = 272; median age, 62 years; 73.9% men; 73.9% East Asian). Patients underwent six treatment cycles and maintenance treatment until unacceptable toxicity or disease progression.
OS served as the primary endpoint. Secondary endpoints included PFS, overall response rate and duration of response per RECIST version 1.1, health-related quality of life and safety.
Median follow-up was 11.8 months for the tislelizumab combination group and 11.7 months for the chemotherapy-alone group.
Findings
Results showed statistically significant improvement in median OS with the tislelizumab combination compared with chemotherapy alone (17.2 months vs. 12.6 months; HR = 0.74; 95% CI, 0.59-0.94).
Researchers also observed longer median PFS (7.2 months vs. 5.9 months; HR = 0.67; 95% CI, 0.55-0.83), a higher ORR (50.4%; 95% CI, 44.3-56.4 vs. 43%; 95% CI, 37.1-49.1) and longer median duration of response (9 months; 95% CI, 8.2-19.4 vs. 7.1 months; 95% CI, 5.7-8.3) with the tislelizumab regimen vs. chemotherapy alone.
Patients assigned the combination reported better health-related quality of life, and researchers observed no new adverse events among either treatment group.
Treatment discontinuation occurred more often in the tislelizumab group (22.4% vs. 12.1%). However, grade 3 or higher treatment-associated adverse events (64.7% vs. 62.9%), serious treatment-associated adverse events (42.3% vs. 36.8%) and treatment-associated adverse events leading to death (8.8% vs. 7.7%) appeared similar between the groups.
“The addition of tislelizumab to chemotherapy not only did not worsen quality of life, but suggested better quality of life, as indicated by maintenance of global health status, physical functioning and greater reduction in the general stomach cancer symptoms,” Moehler said. “There was also a trend towards reduction in fatigue, pain, discomfort and upper gastrointestinal symptoms with tislelizumab plus chemotherapy.”
Implications
The findings suggest tislelizumab plus chemotherapy is a new first-line treatment option for this patient population, Moehler said.
“This study continues as a double-blind study toward OS final analysis in the intention-to-treat population,” he said. “Results will be presented later this year.”
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Moehler MH, et al. Abstract 286. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan. 19-21, 2023; San Francisco.
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