The FDA has accepted the supplemental biologics license application (sBLA) for durvalumab (Imfinzi; AstraZeneca) to treat patients with resectable, early-stage, and locally advanced—stages II, III, or IVA—gastric and gastroesophageal (G/GEJ) cancers, granting the agent priority review status and breakthrough therapy designation, according to a news release from AstraZeneca.1
Gastric cancers have a high rate of recurrence, necessitating novel treatment options. | Image Credit: © Gromik – stock.adobe.com
These FDA actions are based on positive data observed in the phase 3, multinational, double-blind, randomized MATTERHORN trial, the results of which were presented at the 2025 American Society of Clinical Oncology Annual Meeting and published in the New England Journal of Medicine. In combination with a chemotherapy regimen (fluorouracil, leucovorin, oxaliplatin, and docetaxel; [FLOT]), durvalumab elicited meaningful improvements in event-free survival (EFS), the study’s primary end point, compared with FLOT alone.1,2
“This priority review reinforces the potential for a perioperative approach with [durvalumab] to transform care for patients with early gastric and gastroesophageal junction cancers, who frequently face disease recurrence or progression even after curative-intent surgery and perioperative chemotherapy,” Susan Galbraith, executive vice president of oncology hematology research and development at AstraZeneca, said in the news release. “This novel treatment is the only immunotherapy-based regimen to show a statistically significant reduction in the risk of progression, recurrence, or death in this setting, and if approved, is poised to change the clinical paradigm.”1
Detailed Results from the MATTERHORN Trial
MATTERHORN investigators sought to evaluate the impact of adding durvalumab to the standard-of-care FLOT regimen for resectable G/GEJ cancers. Researchers estimate that about 1 in 4 patients with G/GEJ cancer who undergo surgery with curative intent develop recurrent disease within 1 year, highlighting a major area of unmet care. Given the high recurrence rates attributed to G/GEJ cancers, the authors speculated that adding durvalumab immunotherapy to standard care would improve outcomes and lessen recurrence.1-3
Patients with G/GEJ cancer were randomly assigned to receive either 1500 mg of durvalumab or placebo every 4 weeks, plus FLOT for 4 cycles—2 cycles each of neoadjuvant and adjuvant therapy, respectively—followed by durvalumab or placebo every 4 weeks for 10 cycles. The primary end point was EFS, while key secondary end points included overall survival (OS) and pathological complete response (pCR), according to the authors.2
In total, 474 patients each were randomly assigned to the durvalumab and placebo groups. The authors found that 2-year EFS was 67.4% among durvalumab-treated patients, whereas it was 58.5% in the placebo group (hazard ratio [HR] = 0.71 [95% CI, 0.58–0.86]; P < .001). Regarding OS rate, investigators measured an OS of 75.7% in the durvalumab group and 70.4% in the placebo group, while pCR was determined to be about 19.2% in the durvalumab-treated patients and 7.2% in the placebo patients.2
Safety observations were consistent with the known tolerability profiles of both FLOT and durvalumab, with similar rates of grade 3 or higher adverse events between the 2 treatment arms.1,2
Durvalumab Continues to Demonstrate Efficacy in Wide Range of Cancers
As a human monoclonal antibody that can block the interaction of PD-L1, durvalumab is designed to counter a tumor’s immune-evading mechanisms while allowing for stronger immune responses against a cancer. Durvalumab is a standard-of-care option for a series of cancers and is approved for the treatment of unresectable non-small cell lung cancer, limited-stage small cell lung cancer, and muscle-invasive bladder cancer.1,4,5
Pharmacists are pivotal in counseling patients on the use of durvalumab for the treatment of its approved indications. Given the myriad indications for durvalumab, it is understandable for a patient to feel overwhelmed or confused when considering whether durvalumab is the right choice for their treatment. Patients can be assured by their pharmacists as to the proven safety and efficacy of durvalumab, solidified in multiple extensive phase 3 trials.
For patients with G/GEJ cancers, the granting of priority review and breakthrough designation by the FDA to durvalumab signifies the growing potential for the agent to transform the treatment paradigm for this population. Patients and pharmacists should remain aware and stay updated on durvalumab’s clinical development pipeline for this indication and be prepared if the agent eventually becomes approved for this treatment indication.