MATTERHORN: Durvalumab Plus FLOT Improves EFS and pCR in Gastric, GEJ Cancers

New high-level results from the phase III MATTERHORN trial have demonstrated the efficacy of perioperative durvalumab with standard-of-care FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) chemotherapy over perioperative chemotherapy alone for the treatment of resectable early-stage gastric and gastroesophageal junction (GEJ) cancers.

The global trial involved 948 patients who were randomized to receive 1500 mg of durvalumab with FLOT chemotherapy or placebo with FLOT chemotherapy every 4 weeks for 2 cycles before surgery. Patients were then administered durvalumab or placebo every 4 weeks for up to 12 cycles after surgery, including 2 cycles of durvalumab or placebo plus FLOT chemotherapy and 10 additional cycles of durvalumab or placebo monotherapy.

The primary end point was event-free survival (EFS), defined as the time from randomization until progression precluding surgery or requiring non-protocol therapy, local or distant recurrence or progression of disease, or death from any cause.

Key secondary end points included pathologic complete response (pCR), defined as the proportion of patients with no detectable cancer cells in resected tumor tissue after neoadjuvant therapy, and overall survival.

According to previous trial data from an interim analysis of pCR, the durvalumab combination more than doubled the pCR rate compared with neoadjuvant chemotherapy alone (19% vs 7%, odds ratio, 3.08; P<0.00001).

Yelena Janjigian, MD, of Memorial Sloan Kettering Cancer Center, the principal investigator in the trial, noted that the data 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.”

The safety profile of the combination was consistent with the known profiles of each treatment, and no new safety findings were observed. Data will be presented at a forthcoming medical meeting.