Adding Imfinzi to FLOT Regimen Improves Cancer-Free Survival in Patients with Gastroesophageal Cancer

Gastric and gastroesophageal junction (GEJ) cancer are among the top five leading causes of cancer mortality globally. In 2025 alone, 1.2 million deaths related to these diseases are expected worldwide. In addition, gastric and esophageal cancers have been among those on the rise in younger populations.

For patients with operable tumors, resection surgery is a primary form of treatment, and standard therapy before and after surgery consists of a chemotherapy regimen called FLOT. It includes the drugs 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel. FLOT is used to reduce tumor size before surgery and help eliminate remaining cancer cells after surgery. However, cancer recurrence rates are still high even with FLOT treatment.

Research from the Memorial Sloan Kettering Cancer Center could change the outlook for people living with gastric or GEJ cancer. The MATTERHORN phase 3 trial tested the addition of a checkpoint inhibitor to the standard FLOT regimen before and after tumor resection.

Immune checkpoint inhibitors, a type of immunotherapy, work by blocking proteins that prevent T cells from binding to and destroying cancer cells. Imfinzi (durvalumab) is a checkpoint inhibitor that the FDA has approved for the treatment of lung, liver, bladder, endometrial and biliary tract cancer. The drug’s maker, AstraZeneca, issued a press release today that Imfinzi has been approved in the European Union (EU) as a resectable muscle-invasive bladder cancer in combination with gemcitabine and cisplatin as neoadjuvant treatment followed by its use as monotherapy adjuvant treatment after radical cystectomy.

In the MATTERHORN trial, 948 participants from over 100 trial centers in 20 countries who had gastric or GEJ cancer were randomized to receive FLOT plus Imfinzi or FLOT plus placebo four to eight weeks before resection surgery and after surgery.

Yelana Janjigian, M.D.

The study, led by Yelena Y. Janjigian, M.D., chief of gastrointestinal medical oncology at Memorial Sloan Kettering, demonstrated that adding Imfinzi to the standard chemotherapy regimen significantly improved event-free survival. The study results were simultaneously published last month in the New England Journal of Medicine (NEJM) and presented at a plenary session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. Plenary sessions feature research with the potential to have a significant impact on oncology practice.

The percentage of participants who remained event-free at 18 months was 73.2% in the Imfinzi group compared with 63.6% in the placebo group, according to the results reported in NEJM. At 24 months, the difference had increased, with 67.4% in the Imfinzi group event-free compared with 58.5% in the placebo group.

Overall, 145 participants (30.6%) in the Imfinzi group died from any cause compared with 176 participants (37.1%) in the placebo group. Overall survival at 18 months was 81.1% in the Imfinzi group and at 77.1%, slightly less, in the placebo group. At 24 months, there was a slightly bigger difference: 75.7% in the Imfinzi group compared with 70.4% in the placebo group

Adding Imfinzi did not increase the risk of serious adverse events, with common side effects being nausea, vomiting, diarrhea, and neutropenia. Additionally, adding the checkpoint inhibitor did not prevent or delay surgery for participants.

According to the authors, the trial results support the use of Imfinzi in combination with standard FLOT treatment as a new standard of care for patients with gastroesophageal cancer.

“For gastroesophageal cancer patients to go through surgery and chemo, it’s devastating to have a recurrence of the cancer,” Janjigian said in a news release. “This trial shows that adding immunotherapy to chemo before and after surgery can dramatically improve the chance that cancer won’t return,” she added.