Gastric cancer is the fifth most prevalent cancer globally and a leading cause of cancer-related mortality, with nearly 1 million new cases. GEJ cancer, a subset at the junction of the stomach and esophagus, shares similar treatment challenges. As per the DelveInsight estimates, the total number of incident cases of gastric cancer (including GEJ) in the United States was 29,000 in 2024, which is expected to increase during the forecast period (2025-2034).

Despite surgery and chemotherapy, recurrence remains common and survival rates are poor, with only about half of patients alive at five years. There is a significant unmet need for more effective perioperative strategies, especially as cases rise in younger populations.

The MATTERHORN trial (NCT04592913), presented at ASCO 2025, evaluated durvalumab combined with FLOT chemotherapy (5-FU, leucovorin, oxaliplatin, and docetaxel) in 948 patients with resectable Stage II–IVA gastric or GEJ adenocarcinoma. Patients were randomized to receive durvalumab or placebo alongside FLOT, both pre-and post-surgery, followed by maintenance immunotherapy.

Durvalumab significantly improved EFS, with the median EFS not reached compared to 32.8 months in the placebo group. At 24 months, EFS and OS rates were higher in the durvalumab arm (67% and 76%) vs. placebo (59% and 70%). The pCR rate more than doubled (19% vs. 7%), and disease-free survival also favored the durvalumab group. Safety was consistent across arms, with no unexpected toxicities.

Importantly, benefits were observed across diverse subgroups—including age, region, nodal status, and tumor site—highlighting the potential for broad clinical use.

KOL insights

“Despite receiving curative-intent surgery and chemotherapy, patients with gastric and gastroesophageal cancers frequently develop recurrent disease. Results from the MATTERHORN trial showed that more than two-thirds of patients treated with a durvalumab-based perioperative regimen had not experienced a recurrence or were progression-free after two years. This new treatment approach should become the new standard of care in this setting based on these results.” – Expert Opinion

“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.” – Expert Opinion

Conclusion 

IMFINZI, a human monoclonal antibody, is designed to restore anti-tumor immune responses by targeting PD-L1 and blocking its interaction with PD-1 and CD80. This mechanism has made it an important therapeutic option across several cancer types, including unresectable hepatocellular carcinoma (in combination with IMJUDO [tremelimumab]), biliary tract cancer (with chemotherapy), and non-small cell lung cancer in earlier stages of the disease.

Despite curative surgery and chemotherapy, recurrence rates remain high in gastric and gastroesophageal cancers. The MATTERHORN trial revealed that over two-thirds of patients receiving durvalumab-based perioperative therapy remained recurrence-free and progression-free at two years. These compelling results support making this approach the new standard of care. In this study, the addition of durvalumab to the standard perioperative FLOT chemotherapy regimen demonstrated significant clinical benefit in patients with resectable gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. The combination notably improved EFS, more than doubled the rate of pathologic complete response (pCR) compared to FLOT alone, and showed a favorable trend toward improved overall survival (OS)—all without introducing new safety concerns.

These results are particularly impactful in the context of gastric and GEJ cancers, where long-term survival remains poor and therapeutic progress has been limited. The consistent efficacy observed across key patient subgroups highlights the potential for durvalumab plus FLOT to redefine the perioperative treatment landscape.

As immunotherapy continues to transform cancer care, this well-tolerated combination represents a promising new approach in the curative-intent setting. By reducing the risk of recurrence and extending survival, it may significantly increase the chance of cure for patients with early-stage G/GEJ adenocarcinoma. Pending regulatory review and final overall survival data, the findings from the MATTERHORN trial strongly support the integration of IMFINZI into standard perioperative treatment strategies, offering a meaningful advance in the management of resectable gastric and gastroesophageal cancers.