Durvalumab Combo Meaningfully Improves EFS in Advanced Gastric/GEJ Cancer

Prior interim analysis results from the MATTERHORN trial showed that the durvalumab combination elicited a pathological complete response (pCR) rate of 19% vs 7% with chemotherapy alone.

Combining durvalumab (Imfinzi) with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) produced a clinically meaningful and statistically significant event-free survival (EFS) improvement vs chemotherapy alone in patients with resectable locally advanced gastric and gastroesophageal junction (GEJ) cancers, according to a press release on interim analysis findings from the phase 3 MATTERHORN trial (NCT04592913).1

Durvalumab plus chemotherapy before surgery followed by adjuvant durvalumab plus chemotherapy and then durvalumab monotherapy reached the trial’s primary end point of EFS. Additionally, investigators noted a strong trend towards improved overall survival (OS) with the durvalumab combination at the time of interim analysis. The trial will formally evaluate OS at the final analysis.

The safety profile of durvalumab and FLOT in the MATTERHORN trial was comparable with prior reports of each individual agent. Investigators will present detailed results from the study at a future medical meeting and share their findings with regulatory authorities across the world.

“Despite receiving curative-intent chemotherapy and surgery, patients with gastric cancer commonly [have] disease recurrence and have a poor prognosis,” principal study investigator Yelena Y. Janjigian, MD, chief attending physician of the Gastrointestinal Medical Oncology Service at Memorial Sloan Kettering Cancer, stated in the press release.1 “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.”

Prior interim analysis results from the MATTERHORN trial showed that the durvalumab combination elicited a pathological complete response (pCR) rate of 19% vs 7% with chemotherapy alone (odds ratio, 3.08; P <.00001).2

In the international phase 3 MATTERHORN trial, 948 patients were randomly assigned to receive durvalumab at 1500 mg or placebo plus FLOT every 4 weeks for 2 cycles before surgery. Following surgery, patients received durvalumab or placebo every 4 weeks for up to 12 cycles, which included 2 cycles of durvalumab or placebo in combination with FLOT and 10 additional cycles of durvalumab or placebo alone.

The trial’s primary end point was EFS, defined as the time from randomization to disease progression or death per blinded independent central review using RECIST v1.1 guidelines. Secondary end points included OS and pCR, which investigators defined as the proportion of patients with no residual viable tumor in the resected specimens.3

Patients 18 years and older with histologically confirmed gastric or GEJ adenocarcinoma and resectable disease of stage II or higher based on American Joint Committee on Cancer 8th edition criteria were eligible for enrollment on the trial. Other requirements for study entry included having eligibility to undergo radical surgery, no prior anti-cancer therapy for the current malignancy, a World Health Organization or ECOG performance status of 0 or 1, adequate organ and marrow function, availability of tumor samples, and a minimum life expectancy of 24 weeks.

Those with peritoneal dissemination or distant metastasis or adenosquamous cell carcinoma, squamous cell carcinoma, or gastrointestinal stromal tumors were ineligible for study entry. Patients were also unable to enroll if they had current or prior use of immunosuppressive medication within 2 weeks of the first durvalumab dose or a history of allogeneic organ transplantation.

“MATTERHORN is the first phase 3 trial of an immunotherapy to show a statistically significant improvement in [EFS] in patients with resectable gastric and [GEJ] cancers. This perioperative approach with [durvalumab] underscores our commitment to moving into earlier stages of cancer where novel therapies can have the biggest impact on patients’ lives,” Cristian Massacesi, chief medical officer and Oncology Chief Development Officer at AstraZeneca, the developer of durvalumab, concluded.1

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/mr4cxyzd
2. IMFINZI® (durvalumab) plus chemotherapy more than doubled pathologic complete response rate in resectable early-stage gastric and gastroesophageal junction cancers versus chemotherapy alone. News release. AstraZeneca. October 20, 2023. Accessed March 7, 2025. https://tinyurl.com/5n8stp8s
3. Assessing durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer. ClinicalTrials.gov. Updated December 13, 2024. Accessed March 7, 2025. https://tinyurl.com/5fwbed2e