Yelena Janjigian ASCO Plenary: Peri-Operative Chemo-Immunotherapy Delays Recurrence in Patients with Gastric or GE Junction Cancers

An interview with:  Yelena Y Janjigian MD, Medical Oncologist, Chief of Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York USA CHICAGO—A treatment described as “practice-changing”, in which a combination of anti-PD-L1 immunotherapy and chemotherapy was used before and after surgery among patients with resectable gastric or gastroesophageal junction cancers, was reported from the MATTERHORN study at the Plenary Session of the 2025 Annual Meeting of the American Society of Clinical Oncology (ASCO). First author, Medical Oncologist Yelena Y Janjigian MD, who is Chief of the Gastrointestinal Oncology Service at Memorial Sloan-Kettering Cancer Center in New York USA, discussed her findings and their clinical implications with the Audio Journal of Oncology’s Peter Goodwin: INTERVIEW WITH Yelena Y Janjigian MD ASCO ABSTRACT: LBA5 (Janjigian): “Event-free survival in MATTERHORN: A randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC).” Background: FLOT is a perioperative standard of care (SoC) in resectable GC/GEJC, yet recurrence rates remain high. Immune checkpoint inhibitors are approved in combination with chemotherapy in metastatic GC/GEJC, but not in the perioperative setting. The randomized, double-blind, global, Phase 3 MATTERHORN study (NCT04592913) assesses the combination of perioperative durvalumab (D) + FLOT vs placebo (P) + FLOT in participants (pts) with locally advanced, resectable GC/GEJC. The primary endpoint is EFS. Pathologic complete response (pCR) and overall survival (OS) are key secondary endpoints. The trial previously showed a statistically significant gain in pCR for D + FLOT. Here, we report efficacy and safety from the pre-planned interim analysis 2. Methods: Pts aged at least 18 years with histologically confirmed, resectable (Stage II–IVa per American Joint Committee on Cancer 8th edition) untreated G/GEJ adenocarcinoma were randomized 1:1 to D 1500 mg or P every 4 weeks (Q4W) on Day 1 + FLOT on Days 1 and 15 for 4 cycles (2 cycles each neoadjuvant/adjuvant), followed by D 1500 mg or P on Day 1 Q4W for 10 cycles. Pts were stratified by Asia vs non-Asia, clinical lymph node status (positive vs negative) and programmed cell death ligand-1 Tumor Area Positivity score (at least 1% vs less than 1%). Data cutoff was Dec 20, 2024. EFS (time from randomization to progression, local or distant recurrence, or death) superiority for D + FLOT vs P + FLOT was assessed in all randomized pts by a stratified log-rank test (2-sided significance level threshold: 0.0239) on data according to RECIST v1.1 per BICR and/or locally by pathology testing. Results: In total, 948 pts were randomized to receive D + FLOT (n=474) or P + FLOT (n=474); median (m) follow up duration was 31.5 months (mo). Demographic/baseline characteristics were generally similar across treatment arms. D + FLOT demonstrated a statistically significant improvement in EFS vs P + FLOT (hazard ratio [HR] 0.71; 95% confidence interval [CI], 0.58–0.86; p,0.001), mEFS was not reached (NR) with D + FLOT vs 32.8 mo with P + FLOT. The 24-mo EFS rate was higher for D + FLOT vs P + FLOT (Table). mOS was NR for D + FLOT vs 47.2 mo for P + FLOT (HR 0.78; 95% CI, 0.62–0.97; p=0.025; 33.9% maturity) and will be formally assessed at the final analysis. Maximum Grade 3 or 4 adverse event rates were similar between treatment arms; D + FLOT did not delay surgery or initiation of adjuvant therapy vs P + FLOT. Conclusion: D + FLOT demonstrated a statistically significant improvement in EFS vs P + FLOT in pts with resectable GC/GEJC, with an encouraging OS trend. These results support D + FLOT as a potential new global SoC for resectable GC/GEJC. C      

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