Results from an international phase III clinical trial found that treating patients with stage II, III, and IVA resectable gastric cancer and gastroesophageal junction (GEJ) cancer with perioperative durvalumab and FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) helped these patients live longer without cancer progression, recurrence, or disease-related complications compared with placebo and FLOT chemotherapy alone. The research is being presented during the Plenary Session at the 2025 ASCO Annual Meeting (Abstract LBA5).
About the Study
“Despite advances in treatment and biomarker development, cure rates for early-stage gastroesophageal cancer remain below 50%, with most recurrences occurring within two years of surgery. MATTERHORN is the first global, randomized phase III trial to show improved event-free survival with an immunotherapy-based regimen in resectable gastric and gastroesophageal junction cancers. The use of immunotherapy in earlier-stage cancers, as demonstrated in this perioperative approach with durvalumab, can reduce the risk of recurrence and improve cure rates,” said lead study author Yelena Y. Janjigian, MD, Chief of the Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center in New York, New York.
The MATTERHORN randomized trial tested if adding durvalumab to the FLOT chemotherapy regimen before and after surgery, with follow-up treatment with durvalumab only, improved outcomes for patients with stage II, III, or IVA untreated, resectable gastric cancer and GEJ cancer. The study included 948 patients with a median age of 62 years. The patients lived in Europe (53%), Asia (19%), South America (19%) and North America (9%).
There were 474 patients randomly assigned to receive perioperative treatment with durvalumab plus FLOT chemotherapy before and after surgery, followed by treatment with durvalumab alone. There were 474 patients randomly assigned to receive perioperative treatment with a placebo plus FLOT chemotherapy before and after surgery, followed by treatment with placebo alone. Most patients had gastric cancer (68% in the durvalumab plus FLOT arm vs 67% in the placebo plus FLOT arm). In the durvalumab plus FLOT arm, 69% of patients were male, and the median age was 62 years.
Key Findings
There was a statistically significant improvement in event-free survival between the durvalumab with FLOT arm compared with the placebo and FLOT arm. Patients in the durvalumab plus FLOT arm experienced a 29% better event-free survival than those in the placebo plus FLOT arm (hazard ratio [HR] = 0.71; 95% confidence interval [CI] = 0.58–0.86; P < .001). The median event-free survival in the placebo plus FLOT arm was 32.8 months.
In the durvalumab plus FLOT arm, the median event-free survival had not been reached at the time of reporting—meaning that more than half of the participants in the durvalumab plus FLOT arm had not experienced cancer recurrence, progression, or complications related to treatment.
At 12 months, the durvalumab plus FLOT arm achieved an event-free survival rate of 78.2% (95% CI = 74.1%–81.7%), compared with 74% (95% CI = 69.7%–77.8%) in the placebo plus FLOT group. The difference increased at 24 months, there was a larger difference: the durvalumab plus FLOT group achieved an EFS rate of 67.4% (95% CI = 62.9%–71.6%) compared with 58.5% (95% CI = 53.8%–63.0%) in the placebo plus FLOT arm.
The median overall survival has not yet been reached for the durvalumab plus FLOT arm. The median overall survival for the placebo plus FLOT arm was 47.2 months (HR = 0.78; 95% CI = 0.62–0.97; P = .025).
The two treatment arms had a similar rate of grade 3 and 4 adverse events. The most common adverse effects in the durvalumab plus FLOT arm were diarrhea, nausea, neutropenia, hair loss, and decreased appetite. Taking durvalumab with FLOT also did not delay surgery or any additional treatments.
“The pace of therapeutic advances in upper gastrointestinal cancers has accelerated in recent years. Now, the MATTERHORN trial shows that perioperative treatment with FLOT plus durvalumab is better than FLOT alone in reducing the risk of recurrence. 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,” said Pamela Kunz MD, PhD, Director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and Yale Cancer Center and an ASCO expert in gastrointestinal cancers.
Disclosure: This study was funded by AstraZeneca. For full disclosures of the study authors, visit coi.asco.org.
