Perioperative Durvalumab Plus Chemo Meets EFS End Point in Resectable Gastric/GEJ Cancer

Neoadjuvant durvalumab (Imfinzi) plus FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel), followed by adjuvant durvalumab plus FLOT, then durvalumab monotherapy, generated a statistically significant and clinically meaningful improvement in event-free survival (EFS) vs perioperative placebo plus FLOT in patients with resectable, stage II, III, or IVA gastric and gastroesophageal junction (GEJ) cancer, meeting the primary end point of the phase 3 MATTERHORN trial (NCT04592913).1

Findings from an interim analysis announced by AstraZeneca also showed that a strong overall survival (OS) trend was observed favoring the durvalumab arm. Follow-up will continue before OS—a key secondary end point—is formally assessed during the trial’s final analysis.

Safety data for durvalumab and FLOT were consistent with the known profiles of each agent, and no new safety signals were reported. Full data from the interim analysis will be presented at an upcoming medical conference and shared with global health authorities.

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

Previously reported data from the first interim analysis of MATTERHORN presented at the 2023 ESMO Congress showed that patients in the durvalumab arm (n = 474) achieved a pathological complete response (pCR) rate of 19% per central review assessment compared with 7% for those in the placebo arm (n = 474; OR, 3.08; 95% CI, 2.03-4.67; P < .00001).2 The CR/near-CR rates were 27% and 14%, respectively (OR, 2.19; 95% CI, 1.58-3.04; P < .00001).

The multicenter, global, double-blind, placebo-controlled MATTERHORN study enrolled patients at least 18 years of age with histologically documented resectable gastric/GEJ adenocarcinoma who had not received any prior anticancer therapy for their current malignancy. Patients were required to undergo radical surgery; have a WHO/ECOG performance status of 0 or 1; have adequate organ and marrow function; and have a life expectancy of at least 24 weeks.

Patients were excluded if they had peritoneal dissemination or distant metastasis; had denosquamous cell carcinoma, squamous cell carcinoma, or gastrointestinal stromal tumor; received immunosuppressive drugs within 14 days of first dose of durvalumab/placebo; or had a history of allogenic organ transplant.

Investigators randomly assigned 948 patients 1:1 between the 2 arms.1 In the experimental arm, patients received 1500 mg of durvalumab plus FLOT once every 2 weeks prior to surgery, then adjuvant durvalumab plus FLOT once every 4 weeks for 2 cycles, followed by durvalumab monotherapy once every 4 weeks for 10 additional cycles. In the control arm, patients received the same FLOT regimen with placebo in place of all durvalumab doses.

Along with the primary end point of EFS, secondary end points included OS and pCR rate.3

Previously reported safety data from the study’s first interim analysis demonstrated that any-grade, any-cause adverse effects (AEs) occurred in 99% of patients in both arms.2 The rates of grade 3/4 AEs were 69% for the durvalumab arm vs 68% for the placebo arm. In the experimental arm, AEs led to death, surgery delay, discontinuation of durvalumab/placebo, and discontinuation of FLOT in 5%, 3%, 7%, and 23% of patients, respectively. These respective rates were 4%, 2%, 6%, and 20% in the placebo arm.

Any-grade AEs possibly related to study treatment were reported in 95% of patients in the durvalumab arm compared with 94% of patients in the placebo arm. The respective rates of grade 3/4 AEs that were possibly treatment related were 58% and 56%. Treatment-related AEs leading to death occurred in 1% of patients (n = 5) in the experimental arm vs less than 1% (n = 2) in the control arm.

The most common grade 3/4 AEs possibly related to treatment included neutropenia (durvalumab arm, 20%; placebo arm, 21%), decreased neutrophil count (19%; 22%), diarrhea (5%; 4%), and decreased white blood cell count (5%; 6%).

References

1. Imfinzi-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://www.astrazeneca.com/media-centre/press-releases/2025/imfinzi-improved-efs-in-early-stage-gastric-cancer.html
2. Janjigian YY, Al-Batran S, Wainberg ZA, et al. Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the global, phase III MATTERHORN study. Ann Oncol. 2023;34(suppl 2):S1315-S1316. doi:10.1016/j.annonc.2023.10.074
3. Assessing durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer. ClinicalTrials.gov. Updated December 13, 2024. Accessed March 7, 2025. https://clinicaltrials.gov/study/NCT04592913