Perioperative durvalumab in gastric and gastroesophageal junction cancer Journal Article
| Authors: | Janjigian, Y. Y.; Al-Batran, S. E.; Wainberg, Z. A.; Muro, K.; Molena, D.; Van Cutsem, E.; Hyung, W. J.; Wyrwicz, L.; Oh, D. Y.; Omori, T.; Moehler, M.; Garrido, M.; Oliveira, S. C. S.; Liberman, M.; Oliden, V. C.; Smyth, E. C.; Stein, A.; Bilici, M.; Alvarenga, M. L.; Kozlov, V.; Rivera, F.; Kawazoe, A.; Serrano, O.; Heilbron, E.; Negro, A.; Kurland, J. F.; Tabernero, J.; for the MATTERHORN Investigators |
| Article Title: | Perioperative durvalumab in gastric and gastroesophageal junction cancer |
| Abstract: | Background Perioperative FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) is a standard therapy for resectable gastric and gastroesophageal junction adenocarcinomas, but recurrence rates remain high. Immunotherapy plus chemotherapy may improve outcomes. Methods In a phase 3, multinational, double-blind, randomized trial, we assigned participants with resectable gastric or gastroesophageal junction adenocarcinoma, in a 1:1 ratio, to receive durvalumab at a dose of 1500 mg or placebo every 4 weeks plus FLOT for 4 cycles (2 cycles each of neoadjuvant and adjuvant therapy), followed by durvalumab or placebo every 4 weeks for 10 cycles. The primary end point was event-free survival; secondary end points included overall survival and pathological complete response. Results A total of 474 participants were randomly assigned to the durvalumab group, and 474 to the placebo group (median follow-up, 31.5 months; interquartile range, 26.7 to 36.6). Two-year event-free survival (Kaplan-Meier estimate) was 67.4% among the participants in the durvalumab group and 58.5% among those in the placebo group (hazard ratio for event or death, 0.71; 95% confidence interval [CI], 0.58 to 0.86; P<0.001). Two-year overall survival was 75.7% in the durvalumab group and 70.4% in the placebo group (piecewise hazard ratio for death during months 0 to 12, 0.99 [95% CI, 0.70 to 1.39], and during the period from month 12 onward, 0.67 [95% CI, 0.50 to 0.90]; P=0.03 by a stratified log-rank test [exceeding the significance threshold of P<0.0001]). The percentage of participants with a pathological complete response was 19.2% in the durvalumab group and 7.2% in the placebo group (relative risk, 2.69 [95% CI, 1.86 to 3.90]). Adverse events with a maximum grade of 3 or 4 were reported in 340 participants (71.6%) in the durvalumab group and in 334 (71.2%) in the placebo group. The percentage of participants with delayed surgery was 10.1% and 10.8%, respectively, and the percentage with delayed initiation of adjuvant treatment was 2.3% and 4.6%. Conclusions Perioperative durvalumab plus FLOT led to significantly better event-free survival outcomes than FLOT alone among participants with resectable gastric or gastroesophageal junction adenocarcinoma. © 2025 Massachusetts Medical Society. |
| Keywords: | controlled study; aged; middle aged; clinical trial; mortality; fluorouracil; chemotherapy, adjuvant; neoadjuvant therapy; antineoplastic agent; adenocarcinoma; randomized controlled trial; antineoplastic combined chemotherapy protocols; docetaxel; monoclonal antibody; antibodies, monoclonal; multicenter study; folinic acid; adjuvant chemotherapy; surgery; phase 3 clinical trial; kaplan meier method; drug therapy; oxaliplatin; double blind procedure; double-blind method; leucovorin; stomach neoplasms; esophagus tumor; esophageal neoplasms; stomach tumor; esophagogastric junction; kaplan-meier estimate; gastroesophageal junction; gastroenterology; hematology/oncology; humans; human; male; female; durvalumab; immunological antineoplastic agent; antineoplastic agents, immunological; gastrointestinal tract cancer; treatments in oncology |
| Journal Title: | New England Journal of Medicine |
| Volume: | 393 |
| Issue: | 3 |
| ISSN: | 0028-4793 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2025-07-17 |
| Start Page: | 217 |
| End Page: | 230 |
| Language: | English |
| DOI: | 10.1056/NEJMoa2503701 |
| PUBMED: | 40454643 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Yelena Y. Janjigian -- Source: Scopus |
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