Key Takeaways
- Imfinzi shows 29% risk reduction: The Phase III MATTERHORN trial demonstrated a 29% reduction in the risk of disease progression, recurrence, or death for early-stage gastric and gastroesophageal junction (GEJ) cancer patients treated with Imfinzi.
- First immunotherapy-based perioperative option: If approved, Imfinzi would become the first immunotherapy-based perioperative regimen to show statistically significant benefit in resectable gastric and GEJ cancers.
- FDA grants Priority Review and Breakthrough Therapy: Imfinzi received Priority Review and Breakthrough Therapy Designation, accelerating a potential approval for this high-need patient population.
The FDA has granted Priority Review and Breakthrough Therapy Designation for Imfinzi (durvalumab) in patients with resectable, early-stage, and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers. According to the company, these designations were based on results from the Phase III MATTERHORN trial (NCT04592913), which demonstrated that a perioperative Imfinzi-based regimen, administered before and after surgery alongside chemotherapy, significantly reduced the risk of disease progression, recurrence, or death compared to chemotherapy alone.1
How Could the MATTERHORN Trial Results for Imfinzi Change the Treatment Paradigm for Early-Stage Gastric and GEJ Cancers?
“This Priority Review reinforces the potential for a perioperative approach with Imfinzi 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,” said Susan Galbraith, EVP, oncology hematology R&D, AstraZeneca, in a press release.
MATTERHORN Trial Design and Treatment Approach
- The randomized, double-blind, placebo-controlled, multicenter, global MATTERHORN trial evaluated perioperative Imfinzi treatment in 948 patients with gastric and GEJ cancers.
- Patients were randomly assigned to receive either a 1500 mg fixed dose of Imfinzi plus fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy, or placebo plus FLOT, every four weeks for two cycles before surgery.
- Following surgery, patients continued with either Imfinzi or placebo every four weeks for up to 12 cycles.
- The primary endpoint was event-free survival (EFS), defined as the time from randomization until progression per RECIST 1.1, progression/recurrence during the adjuvant phase, non-RECIST progression precluding surgery, biopsy-confirmed recurrence post-surgery, or death from any cause.
MATTERHORN Trial Key Findings
- Results showed that patients treated with the combination demonstrated a 29% reduction in the risk of disease progression, recurrence, or death compared to chemotherapy alone (HR=0.71; 95% CI: 0.58–0.86; P<0.001).
- Median EFS was not yet reached in the Imfinzi arm compared to 32.8 months in the control arm.
- At one year, 78.2% of patients in the Imfinzi arm were event-free, compared to 74% in the control arm.
- At two years, EFS rates were 67.4% in the Imfinzi arm and 58.5% in the control arm.
- The safety profile of the Imfinzi-FLOT combination was consistent with the known profiles of the individual agents.
- The rate of grade 3 or higher adverse events and surgery complications were similar across both groups.1,2
Esophageal Cancer Context in the United States
According to the American Cancer Society, it is estimated there will be a total of 22,070 new esophageal cancer cases diagnosed in the United States by the end of 2025, with approximately 16,250 deaths. This cancer type makes up approximately 1% of all cancers in the United States, making it less common than in other parts of the world.
