ADDING AN IMMUNOTHERAPY DRUG called Imfinzi (durvalumab) to treatment perioperatively, meaning before and after surgery, led to more people going without cancer returning or progressing in stage II to IVa gastric cancer and gastroesophageal junction (GEJ) cancer. The gastroesophageal junction is where the esophagus and stomach join together. The drug combination is already approved for patients with metastatic cancer, but these recent findings show it may benefit people with earlier-stage cancer as well.

Currently, patients with gastric or GEJ adenocarcinoma that can be removed with surgery are typically given a chemotherapy combination known as FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) perioperatively. The phase III MATTERHORN trial, published June 1, 2025, in the New England Journal of Medicine and presented at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting, evaluated whether adding Imfinzi before and after surgery could improve survival.

Of 948 participants, 474 were given the FLOT plus Imfinzi combination and 474 were given FLOT plus a placebo. Treatment involved Imfinzi or placebo given by IV once every four weeks along with FLOT given every two weeks for four cycles (two before surgery and two after) followed by just Imfinzi or placebo every four weeks for an additional 10 cycles.

At 24 months, 67.4% of the patients in the Imfinzi group had not experienced cancer progression compared with 58.5% in the placebo group, a 29% improvement. Overall survival findings were not ready at the time of this analysis, but available data show a trend of longer survival in people given Imfinzi.

“For patients, this offers a meaningful step forward: better long-term outcomes without major added toxicity,” Yelena Janjigian, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City and the study’s lead author, says. She stresses that the benefits of adding Imfinzi were clear across tumor types, biomarker groups and geographic regions in this international study.

The results of the MATTERHORN trial will change the standard of care for this patient population, says John Strickler, a medical oncologist at Duke Cancer Center in Durham, North Carolina, who was not involved in the study.

“We now know that nearly all patients with gastroesophageal cancer receiving chemotherapy before and after surgery should also receive immunotherapy,” Strickler says, adding that immunotherapy “substantially improves the effectiveness of treatment and increases the chance that cancer will not return after surgery.”

While the benefits of adding immunotherapy to the treatment plan for early-stage gastric cancer are clear, Strickler says researchers continue to look for ways to narrow treatment to those it is most likely to help. “There are still patients who do not benefit from immunotherapy,” he explains. “Looking ahead, additional research is needed to identify those patients most likely to benefit and those patients least likely to benefit. We are striving to develop precision medicine strategies so that we can give the right treatments to the right group of patients.”

The researchers also noted that adding immunotherapy to the FLOT regimen did not increase the risk of serious side effects.

“There was a slight increase in immune-related side effects with durvalumab, which we expected. Serious side effects—called grade 3 or 4—were similar in both groups,” Janjigian says. The safety profile of adding immunotherapy was positive overall and unlikely to delay plans for surgery or chemotherapy, she says.

For some patients, however, immunotherapy may not be advisable, Janjigian says. These include people with certain autoimmune diseases or who have had organ transplants, and those who have stage I disease or significant comorbidities where a less intensive strategy may be more appropriate.

“But for most patients with stage II to III gastric or GEJ adenocarcinoma, this regimen should be strongly considered as a new standard,” she says.

Laura Gesualdi Gilmore is a Chicago-based freelance journalist who covers topics ranging from health and wellness to luxury travel.