MATTERHORN: Durvalumab Plus Chemotherapy for Gastric, Gastroesophageal Junction Cancers

Results from the MATTERHORN phase 3 trial showed that durvalumab plus standard-of-care fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) neoadjuvant chemotherapy more than doubled the pathologic complete response (pCR) rate in patients with resectable, early-stage, and locally advanced gastric cancer (GC) and gastroesophageal junction cancers (GEJC) when compared with chemotherapy alone.

Dr. Salah-Eddin Al-Batran, of the Institute of Clinical Cancer Research, presented the study at the European Society for Medical Oncology Congress 2023.

The trial’s primary end point was event-free survival (EFS), with secondary end points including pCR rate and overall survival. Researchers qualified the pCR rate as the proportion of patients without detectable cancer cells in resected tumor tissue after undergoing neoadjuvant therapy.

The study randomized 948 participants from the United States, Canada, Europe, South America, and Asia, with 474 patients in each trial arm.

Patients received either durvalumab (1500 mg) plus FLOT chemotherapy or placebo plus FLOT chemotherapy every 4 weeks for 2 cycles before surgery. Participants were also given durvalumab or placebo every 4 weeks for up to 12 cycles after surgery. Two of these cycles included durvalumab plus FLOT chemotherapy or placebo plus chemotherapy and 10 cycles of durvalumab or placebo monotherapy.

Investigators observed a statistically significant improvement in pCR in the durvalumab plus FLOT chemotherapy group compared with the FLOT chemotherapy alone group (19% vs 7%, respectively; P=.00001). The combined pCR and near-complete pathological response rate was 27% with durvalumab and 14% with chemotherapy alone.

In surgical patients, the surgery rate and the R0 resection rate were similar in both the durvalumab group (87% and 86%, respectively) and the placebo group (84% and 86%, respectively).

Researchers concluded that durvalumab plus chemotherapy shows promise for patients with GC and GEJC. “The addition of durvalumab to perioperative FLOT chemotherapy demonstrated a clinically meaningful and statistically significant improvement in pCR in resectable GC and GEJC, with a tolerable safety profile,” they wrote.

Investigators noted that the MATTERHORN study is continual, with a primary end point of EFS.