Durvalumab Plus Chemotherapy Boosts EFS in Gastric/GEJ Cancer

Stomach cancer, gastric cancer, symptoms, stages, treatment, 3d illustration: © Crystal Light - stock.adobe.com

Perioperative treatment with durvalumab (Imfinzi) plus fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) compared with chemotherapy alone in patients with resectable, early-stage and locally advanced gastric and gastroesophageal junction cancers, according to data from the phase 3 MATTERHORN trial (NCT04592913).¹

At this interim analysis, a strong trend was also seen for the study’s secondary end point of overall survival (OS) that was in favor of the durvalumab-based regimen. The trial will continue to follow OS, which will be formally assessed at the final analysis.

Additionally, the safety profile for the durvalumab and FLOT chemotherapy combination was consistent with previously reported findings for each agent. Further, no new safety signals were observed.

“Despite receiving curative-intent chemotherapy and surgery, patients with gastric cancer commonly face disease recurrence and have a poor prognosis. These exciting data from MATTERHORN show that a durvalumab-based perioperative regimen resulted in a clinically meaningful improvement in patient outcomes, including decreasing the risk of the cancer coming back,” said Yelena Y Janjigian, MD, Chief Attending Physician of the Gastrointestinal Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York and principal investigator in the trial, in a press release.

These data will be presented at an upcoming medical meeting and shared with global regulatory authorities.

About the MATTERHORN Trial

The international, double-blind, placebo-controlled phase 3 MATTERHORN study enrolled and randomly assigned 948 patients in a 1:1 fashion to receive 1500 mg of durvalumab or placebo every 4 weeks plus FLOT every 2 weeks on days 1 and 15 for 4 cycles prior to surgery.² Postoperative treatment consisted of 2 additional doses of durvalumab or placebo plus 4 doses of FLOT followed by 10 doses of maintenance durvalumab or placebo.

The study enrolled patients from Asia, Europe, North America, and South America who had stage II, III, and IVA gastric or GEJ adenocarcinoma and an ECOG performance status of 0 or 1. Patients were not eligible if they had evidence of metastasis, and they were not permitted to have received prior treatment.

The primary end point of the trial was EFS. Secondary end points included pCR per central review based on modified Ryan criteria and overall survival.

Previously, the MATTERHORN trial showed that when compared with a regimen of FLOT plus placebo (n = 474), durvalumab plus FLOT (n = 474) demonstrated a statistically significant improvement in pathological complete response (pCR) rate in patients with gastric and GEJ adenocarcinoma.²

At an interim analysis, rates were 19% by central review vs 7%, respectively (Δ, 12%; OR, 3.08; 95% CI, 2.03-4.67; P <.00001), meeting a secondary end point of the trial. The durvalumab regimen also improved combined complete and near-complete pathological response vs placebo plus FLOT, at 27% and 14%, respectively (Δ12%; OR, 2.19; 95% CI, 1.58-3.04; P <.00001).

“Essentially, MATTERHORN is the first global study, a phase 3 randomized trial, totally double-blinded, where patients got perioperative durvalumab [Imfinzi] plus FLOT in resectable cancers vs FLOT alone…Adverse events were similar, and they were well tolerated,” explained Yanghee Woo, MD, surgical oncologist in the Division of Surgical Oncology, associate professor in the Department of Surgery, vice chair of international affairs, director of the Gastroenterology and Minimally Invasive Therapies Program at City of Hope, in an interview with Targeted Oncology^TM.

REFERENCES

1. IMFINZI® (durvalumab)-based regimen demonstrated statistically significant and clinically meaningful improvement in event-free survival in resectable early-stage gastric and gastroesophageal junction cancers. News release. AstraZeneca. March 7, 2025. Accessed March 7, 2025. https://tinyurl.com/mserfmx5

2. Janjigian YY, Al-Batran SE, Wainberg ZA, et al. Pathological complete response (pCR) to 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) with or without durvalumab (D) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): subgroup analysis by region from the phase 3, randomized, double-blind MATTERHORN study. J Clin Oncol. 2024;42(suppl 3):LBA246. doi:10.1200/JCO.2024.42.3_suppl.LBA246