Positive high-level results from the MATTERHORN Phase III trial showed perioperative treatment with AstraZeneca plc (LON:AZN) Imfinzi (durvalumab) in combination with standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival (EFS). Patients were treated with neoadjuvant Imfinzi in combination with chemotherapy before surgery, followed by adjuvant Imfinzi in combination with chemotherapy, then Imfinzi monotherapy. The trial evaluated this regimen versus perioperative chemotherapy alone for patients with resectable, early-stage and locally advanced (Stages II, III, IVA) gastric and gastroesophageal junction (GEJ) cancers.
For the secondary endpoint of overall survival (OS), a strong trend was observed in favour of the Imfinzi-based regimen at this interim analysis. The trial will continue to follow OS, which will be formally assessed at the final analysis.
Gastric cancer is the fifth leading cause of cancer death globally, with nearly one million people diagnosed each year.1 In 2024, there were roughly 43,000 drug-treated patients in the US, European Union (EU) and Japan in early-stage and locally advanced gastric or GEJ cancer.2 Approximately 62,000 patients in these regions are expected to be newly diagnosed in this setting by 2030.3
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, said: “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.”
Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “MATTERHORN is the first Phase III trial of an immunotherapy to show a statistically significant improvement in event-free survival in patients with resectable gastric and gastroesophageal junction cancers. This perioperative approach with Imfinzi underscores our commitment to moving into earlier stages of cancer where novel therapies can have the biggest impact on patients’ lives.”
The safety profile for Imfinzi and FLOT chemotherapy was consistent with the known profiles of each medicine, and there were no new safety findings.
In a previously reported interim analysis for the key secondary endpoint of pathologic complete response (pCR), the Imfinzi combination more than doubled the pCR rate compared to neoadjuvant chemotherapy alone (19% versus 7%, odds ratio 3.08; p<0.00001).4
Data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.
References
- World Health Organization. International Agency for Research on Cancer. Stomach Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/7-stomach-fact-sheet.pdf. Accessed March 2025.
- AstraZeneca PLC. Investor Relations Epidemiology Spreadsheet. Available at: https://www.astrazeneca.com/investor-relations.html. Accessed March 2025.
- Kantar Health, validated with SEER stage at diagnosis and Cabasag et al. and Kuzuu et al. 2021.
- Janjigian YY, et al. LBA73 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(S2):S1315 – S1316.
