AstraZeneca’s immunotherapy Imfinzi has proven it can help certain patients with early-stage stomach cancer, according to results from a phase 3 study.
Adding Imfinzi to the chemotherapy regimen of FLOT both before and after surgery lowered the risk of disease recurrence, progression or death by 29% compared with FLOT alone in patients with resectable gastric cancer and gastroesophageal junction (GEJ) cancer.
The data, from the phase 3 Matterhorn trial, will be presented at the 2025 American Society of Clinical Oncology annual meeting.
“This trial defines a new paradigm for patients with early-stage and locally advanced gastric and gastroesophageal junction cancers and shows the benefits of giving our best treatments earlier,” Pamela Kunz, M.D., Ph.D., director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center and someone recognized by the ASCO as an expert in the field, said in a statement.
While immune checkpoint inhibitors have been approved in advanced stomach cancer, Matterhorn was the first positive phase 3 trial in the early-stage setting.
The study enrolled 948 patients with stage 2 to 4a resectable gastric and GEJ cancers. After a median follow-up of 31.5 months, more than half of patients receiving Imfinzi and FLOT were still alive without cancer recurrence, worsening or death, whereas the median event-free survival time for those who received a placebo and FLOT reached 32.8 months.
Subgroup analyses suggested that all patients across different tumor areas, geographic locations and PD-L1 expressions appeared to have benefited from Imfinzi, the study’s lead author Yelena Janjigian, M.D., from Memorial Sloan Kettering Cancer Center told reporters during a press briefing.
The addition of Imfinzi didn’t compromise the chance of a complete resection, which is an important consideration among doctors, as 92% of patients in both arms had complete resections, Janjigian said.
Imfinzi also showed an early favorable trend toward a potential life extension benefit. With just 34% of deaths accrued for the final overall survival analysis, Imfinzi led to a preliminary 22% reduction in the risk of death, although the number has not reached statistical significance.
Imfinzi’s potential overall survival benefit started to show around 12 months and has so far sustained.
Despite the overall positive note, Kunz cautioned about patient selection from a tolerability standpoint because FLOT already has four drugs: 5-fluorouracil, leucovorin, oxaliplatin and docetaxel.
Janjigan described the Imfinzi’s toxicity profile as “relatively expected.” Maximum grade 3 or 4 adverse event rates were similar between the two treatment arms.
Matterhorn uses Imfinzi both before and after surgery in what’s known as a perioperative treatment. The FDA and its external advisors have recently criticized clinical trials using a perioperative design, asking that future trials separate the contribution of presurgery and postsurgery treatments.
That shouldn’t be a regulatory problem for Imfinzi’s perioperative use, AZ’s oncology R&D head, Susan Galbraith, Ph.D., said during a press briefing ahead of the Matterhorn presentation.
FLOT has been a standard perioperative treatment for early stomach cancer, and Imfinzi is being added to that continuous use, Galbraith noted. The FDA raised the perioperative issue when discussing Imfinzi in early-stage non-small cell lung cancer. In that case, chemotherapy was only used before surgery, and AZ’s new regimen is adding Imfinzi to both sides of surgery.
A statistically significant event-free survival showing and a “strong trend” to overall survival constitute a “compelling benefit,” Galbraith said.