Durvalumab/FLOT Cemented as New SOC in Gastric/GEJ Cancers

Results from the phase 3 MATTERHORN study (NCT04592913) led to the FDA approval of durvalumab (Imfinzi) plus 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT)neoadjuvant and adjuvant treatment, followed by single-agent durvalumab as a treatment for patients with resectable gastric and gastroesophageal junction (GEJ) cancers.1

Yelena Y. Janjigian, MD, chief of the Gastrointestinal Oncology Service and Carroll and Milton Petrie Chair at Memorial Sloan Kettering Cancer Center, spoke with CancerNetwork® about the results of the trial and how it has impacted the standard of care in the gastrointestinal space.

In the durvalumab arm, for patients with a pathological complete response (pCR), the 24-month event-free survival (EFS) rate was 92.7% in the durvalumab arm vs 79.4% in the placebo arm (HR, 0.29; 95% CI, 0.08-0.96); for those with a major pCR, EFS rates were matched (HR, 0.32; 95% CI, 0.15-0.68); and for those with any pathological response, the 24-month EFS rates were 78.3% vs 68.0% (HR, 0.60; 95% CI, 0.46-0.79). 2

Janjigian also mentioned how the results were presented at different meetings throughout 2025, including the American Society of Clinical Oncology (ASCO) Annual Meeting, which showed the positive pCR outcomes, leading more clinicians to begin utilizing this regimen for this patient population.3

Transcript:

This is a very important early indicator of the likelihood of cure, and how likely it is that someone’s cancer is going to come back. The patients want to have reassurance…They want to know whether or not their cancer will come back, and knowing that pathologic complete response is a good surrogate for long-term outcomes and long-term survival is a helpful tool, because it can help us, in the future, prioritize certain strategies. Hopefully, we can have early readouts from other studies, but also for each individual patient, the knowledge is so powerful and reassuring to them that their chances of cancer recurrence are low. It’s [quite] helpful.

It’s now the accepted standard combination of durvalumab with FLOT. As you remember, this past summer at ASCO, in the plenary session, I presented the data for the first time, and we saw the positive pathologic complete response rates and the event-free survival. We even got the NCCN Compendium listing and approval in the NCCN guidelines. There are still some physicians who were holding out and waiting for the OS data, and certainly, we were waiting for the OS data until we got the final FDA approval. [We] have unequivocal FDA approval irrespective of PD-L1, so both PD-L1–positive and negative tumors. To show the OS curves so clearly solidified it as the standard [of care]. I just came back from China, and people were talking about the regimen there; the European colleagues are increasingly using it. It’s important, it’s definitive, and it’s clear.

References

1. FDA approves durvalumab for resectable gastric or gastroesophageal junction adenocarcinoma. News release. FDA. November 25, 2025. Accessed December 23, 2025. https://tinyurl.com/mrsfxta8
2. Tabernero J, Al-Batran S-E, Wainberg ZAA, et al. Final overall survival (OS) and the association of pathological outcomes with event-free survival (EFS) in MATTERHORN: a randomised, phase III study of durvalumab (D) plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric / gastroesophageal junction (G / GEJ) adenocarcinoma. Presented at: ESMO 2025 Congress; October 17–20, 2025; Berlin, Germany. Abstract LBA81.
3. Janjigian YY, Al-Batran S-E, Wainberg ZA, et al. Perioperative durvalumab in gastric and gastroesophageal junction cancer. N Engl J Med. 2025;393(3):217-230. doi:10.1056/NEJMoa2503701