‘Relatively Low’ AEs Noted With Durvalumab/FLOT in Gastric/GEJ Cancer

The adverse effects (AEs) associated with durvalumab (Imfinzi) plus 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) were similar to previously reported results for patients with resectable gastric/gastroesophageal (GEJ) cancer. Any-grade AEs were noted in 99.2% of patients in the durvalumab group vs 98.7% in the placebo group. Of note, 59.6% vs 59.1% of patients experienced AEs that were possibly related to components of the treatment.1

Yelena Y. Janjigian, MD, spoke about the AEs observed in the phase 3 MATTERHORN study (NCT04592913). She noted that most clinicians can now identify, treat, and mitigate AEs related to immunotherapy. In the trial, the most common AE was diarrhea, which occurred in 62.3% of patients in the durvalumab group vs 57.6% in the placebo group. Between both groups, AEs leading to death were noted in 5.1% vs 4.3%, respectively.

The durvalumab/FLOT regimen was approved by the FDA in November 2025.2 The indication was for neoadjuvant and adjuvant treatment, followed by single-agent durvalumab as a treatment for patients with resectable gastric and GEJ cancers.

Janjigian is chief of the Gastrointestinal Oncology Service and Carroll and Milton Petrie Chair at Memorial Sloan Kettering Cancer Center.

Transcript:

The most common AEs in the MATTERHORN study were from chemotherapy. This is a combination drug regimen, [including] FLOT chemotherapy. The common [AEs] are neutropenia and alopecia in patients from Asian countries, so, Japan, Taiwan, and the Republic of Korea. The rate of febrile neutropenia was notable. Neuropathy and anorexia are common [AEs] that chemotherapy can cause. The rate of immune-related adverse events was not any higher than you would expect in any other immunotherapy trials, so it was relatively low. In fact, serious immune-related adverse events are relatively rare with anti–PD-1 therapy. Most of the [AEs] are in combination with chemotherapy. We know how to recognize them and mitigate them. Because of MATTERHORN, more doctors are using perioperative therapy, and they are using FLOT. [Fewer] patients are getting chemoradiation. More patients are getting durvalumab and FLOT. The doctors, as they become more comfortable, know how to dose reduce, and use prophylactic growth factors such as GCSF, [that] makes the regimen much more doable in clinical practice.

References

1. Tabernero J. 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.
2. FDA approves durvalumab for resectable gastric or gastroesophageal junction adenocarcinoma. News release. FDA. November 25, 2025. Accessed December 23, 2025. https://tinyurl.com/mrsfxta8