Breaking Down MATTERHORN: Durvalumab Plus FLOT in Gastric Cancer
Arturo Loaiza-Bonilla, MD, MSEd, discusses findings from the MATTERHORN trial in patients with resectable gastric or gastroesophageal junction adenocarcinoma.
The phase 3 MATTERHORN trial (NCT04592913) demonstrated that perioperative durvalumab (Imfinzi) combined with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) significantly improved event-free survival (EFS) in patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma.
At a median follow-up of 31.6 months, median EFS was not reached (95% CI, 40.7-NR) in the durvalumab arm vs 32.8 months (95% CI, 27.9-NR) with placebo (HR, 0.71; P <.001). EFS rates at 24 months were 67% vs 59%, respectively.
In this global, double-blind study, 948 patients with stage II to IVa, non-metastatic gastric/GEJ adenocarcinoma were randomly assigned in a 1:1 fashion to receive perioperative FLOT plus either durvalumab or placebo. Neoadjuvant therapy included 2 cycles of combination therapy; post-surgery, patients received 2 more combination cycles followed by 10 cycles of adjuvant durvalumab or placebo monotherapy.
Durvalumab also improved pathological complete response (pCR) rates (19% vs 7%; P <.001) and disease-free survival (HR, 0.70). Although overall survival (OS) was not yet mature, there was a favorable trend (HR, 0.78; P =.025, not meeting prespecified significance threshold). OS rates at 24 months were 76% vs 70%.
Treatment was well tolerated. Grade 3/4 adverse events (AEs) occurred in 72% of the durvalumab arm vs 71% in the control. Immune-related AEs were more frequent in the durvalumab group (23% vs 7%), with 7% grade 3/4. Discontinuation due to AEs occurred in 30% vs 23%, respectively.
The MATTERHORN trial supports durvalumab plus FLOT as a new perioperative standard for resectable gastric/GEJ adenocarcinoma, offering significant EFS and pCR benefits with manageable toxicity. Further OS data will clarify long-term survival impact.
Here, Arturo Loaiza-Bonilla, MD, MSEd, systemwide chief of hematology and oncology at St. Lukes University Heath Network and co-founder and chief medical officer at Massive Bio, discusses these findings in depth. Watch the full episode of The OncoloGIST HERE.
