What You Should Know

  • A landmark phase 3 trial (MATTERHORN) showed that adding the immunotherapy durvalumab to standard FLOT chemotherapy before and after surgery significantly improves outcomes for early‑stage gastric and gastroesophageal junction cancers, leading to FDA approval.
  • The study demonstrated that introducing immunotherapy earlier in the treatment course is safe, does not interfere with surgery or recovery, and increases the chances of cure for patients with localized disease.
  • Benefits were seen regardless of PD‑L1 status—highlighting that early‑stage tumors may be especially responsive to immune activation—marking a major advancement in curative‑intent treatment for these cancers.

The treatment landscape for early-stage gastric and gastroesophageal junction cancers has entered a new era, following results from a landmark clinical trial showing that adding immunotherapy to standard chemotherapy can significantly improve patient outcomes.

The phase 3 MATTERHORN study evaluated whether combining the anti–PD-L1 immunotherapy durvalumab with FLOT chemotherapy—given before and after surgery—could improve outcomes for patients with non-metastatic, localized adenocarcinoma of the stomach or gastroesophageal junction. Based on the trial’s event-free survival and overall survival data, the U.S. Food and Drug Administration approved the regimen for use in early-stage disease.

“This was really designed to answer a critical question,” says Dr. Yelena Janjigian, physician-scientist and chief of the GI Oncology Service at Memorial Sloan Kettering Cancer Center, before elaborating that the study asked whether “adding immunotherapy to chemotherapy before surgery and after surgery… will help patients live longer and increase chances of cure.”

Receiving Immunotherapy Earlier

Immunotherapy has been used for years in metastatic gastric and esophageal cancers, where some patients experience long-term survival. The MATTERHORN study examined whether moving immunotherapy earlier—when disease burden is lower, and surgery is still possible—could deliver greater benefit.

“We’ve been using immunotherapy for gastric and esophageal adenocarcinoma for metastatic disease for many years,” Dr. Janjigian explains. “Several years ago, we designed this study… to address whether or not treating patients with early-stage disease can help improve outcomes.”

Importantly, the trial showed that adding immunotherapy did not compromise patients’ ability to undergo surgery.

“The addition of immunotherapy… did not impact negatively, did not compromise chances of complete surgery, successful surgery, and patient recovery,” she says. “From that perspective, it is very safe and feasible—but also improves the likelihood of cure.”

One of the most notable findings involved PD-L1, a biomarker often used to predict response to immunotherapy. While more than 80% of early-stage tumors in the study showed PD-L1 overexpression, benefit from immunotherapy was seen regardless of PD-L1 status.

“PD-L1 is a dynamic biomarker, meaning that it may change over time,” Dr. Janjigian notes.

Testing at a single time point may miss meaningful expression, and early-stage disease may be particularly responsive because the tumor and lymph nodes are still intact. “We’re actually able to activate the immune response… irrespective of PD-L1, which is reassuring to see.”

These findings help explain why the FDA approved durvalumab with FLOT for early-stage disease, marking a major step forward in curative-intent treatment for gastric and gastroesophageal cancers.