AstraZeneca’s immunotherapy Imfinzi can help certain patients with early-stage stomach cancer, the company has said, buoyed by the data from the results from its phase 3 Matterhorn trial, which was presented at the 2025 American Society of Clinical Oncology annual meeting in Chicago last week.
Adding Imfinzi (durvalumab) to the chemotherapy combination called 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, reports FiercePharma.
“The trial defines a new paradigm for patients with early-stage and locally advanced gastric and gastro-oesophageal junction cancers and shows the benefits of giving our best treatments earlier,” said Pamela Kunz, MD, PhD, director of the Centre for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Centre.
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 the 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 tumour areas, geographic locations and PD-L1 expressions appeared to have benefited from Imfinzi, said the study’s lead author Yelena Janjigian, MD, from Memorial Sloan Kettering Cancer Centre,
“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.”
Imfinzi also showed an early favourable 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 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 criticised clinical trials using a perioperative design, asking that future trials separate the contribution of pre-surgery and post-surgery treatments.
That shouldn’t be a regulatory problem for Imfinzi’s perioperative use, said AZ’s oncology R&D head, Susan Galbraith. FLOT has been a standard perioperative treatment for early stomach cancer, and Imfinzi is being added to that continuous use, she 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 added.
Imfinzi won crucial approval from US regulators for use in lung cancer back in 2018, to treat non-small cell lung cancer (NSCLC) patients with inoperable mid-stage disease that has not spread widely around the body. It was the first immunotherapy to be approved in this setting.
Study details
Perioperative Durvalumab in Gastric and Gastroesophageal Junction Cancer
Yelena Janjigian, Salah-Eddin Al-Batran, Zev A. Wainberg et al.
Published in New England Journal of Medicine on 1 June 2025
Abstract
Background
Perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) is a standard therapy for resectable gastric and gastro-oesophageal junction adenocarcinomas, but recurrence rates remain high. Immunotherapy plus chemotherapy may improve outcomes.
Methods
In a phase 3, multinational, double-blind, randomised trial, we assigned participants with resectable gastric or gastro-oesophageal junction adenocarcinoma, in a 1:1 ratio, to receive durvalumab at a dose of 1500 mg or placebo every 4 weeks plus FLOT for 4 cycles (2 cycles each of neoadjuvant and adjuvant therapy), followed by durvalumab or placebo every 4 weeks for 10 cycles. The primary end point was event-free survival; secondary end points included overall survival and pathological complete response.
Results
A total of 474 participants were randomly assigned to the durvalumab group, and 474 to the placebo group (median follow-up, 31.5 months; interquartile range, 26.7 to 36.6). Two-year event-free survival (Kaplan–Meier estimate) was 67.4% among the participants in the durvalumab group and 58.5% among those in the placebo group (hazard ratio for event or death, 0.71; 95% confidence interval [CI], 0.58 to 0.86; P<0.001). Two-year overall survival was 75.7% in the durvalumab group and 70.4% in the placebo group (piecewise hazard ratio for death during months 0 to 12, 0.99 [95% CI, 0.70 to 1.39], and during the period from month 12 onward, 0.67 [95% CI, 0.50 to 0.90]; P=0.03 by a stratified log-rank test [exceeding the significance threshold of P<0.0001]). The percentage of participants with a pathological complete response was 19.2% in the durvalumab group and 7.2% in the placebo group (relative risk, 2.69 [95% CI, 1.86 to 3.90]). Adverse events with a maximum grade of 3 or 4 were reported in 340 participants (71.6%) in the durvalumab group and in 334 (71.2%) in the placebo group. The percentage of participants with delayed surgery was 10.1% and 10.8%, respectively, and the percentage with delayed initiation of adjuvant treatment was 2.3% and 4.6%.
Conclusions
Perioperative durvalumab plus FLOT led to significantly better event-free survival outcomes than FLOT alone among participants with resectable gastric or gastro-oesophageal junction adenocarcinoma.
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