Gastric cancer immunotherapy is advancing rapidly, bringing hope for better patient outcomes. Therefore, OncologyTube is excited to share insights from Dr. Syma Iqbal, USC Keck Medicineโs Gastrointestinal Oncology Chief. For example, her leadership in the Southwest Oncology Group and the National Cancer Instituteโs Esophago-Gastric Task Force shapes new treatments for stomach and esophageal cancers.
In her interview at the MOASC Spotlight in Newport Beach, California, Dr. Iqbal discusses the MATTERHORN trial, which tests durvalumab with FLOT chemotherapy. She explains, โAny patient who’s a candidate for perioperative chemotherapy is a candidate for the addition of durvalumab, as long as they don’t have a contraindication to the immunotherapy itself.โ Consequently, this approach suits many patients with stage II-IVa cancers who have good health.
Letโs explore key biomarkers, trial results, and side effect management, guided by Dr. Iqbalโs expertise for doctors, researchers, and patient advocates.
Biomarkers for Personalized Care
First, Dr. Iqbalโs slides highlight biomarkers that guide gastric cancer immunotherapy:
- HER2+ (12-20% of patients): Responds to chemo plus trastuzumab. Additionally, second-line trastuzumab deruxtecan (T-DXd) extends survival (14.7 vs. 11.4 months; HR 0.70, p=0.04).
- MSI-High (3-5%): Shows strong results with PD-1 inhibitors.
- PD-L1 Positive (30-50%): Benefits from therapies like durvalumab.
- Emerging: FGFR2 changes (3-7%) predict responses to drugs like bemarituzumab.
These markers help doctors choose the best treatments. As Dr. Iqbal notes, โThe addition of immunotherapy helps our immune system identify those cells that are being evaded by the mechanisms of inhibition of the T cells. That pathway is clearly important in esophagogastric cancer.โ Thus, testing biomarkers is key to effective care.
MATTERHORN Trial: A Game-Changer
The MATTERHORN study, shared at ASCO 2025 (Janjigian et al., J Clin Oncol 2025; 43: LBA5), proves durvalumab plus FLOT improves results. โThe addition in the perioperative setting has now led to a positive outcome and an improvement in event-free survival in our patients,โ Dr. Iqbal says. For instance, it outperforms FLOT alone, marking a significant step forward in immunotherapy for gastric cancer.
Treatment completion rates were similar:
| Metric | Durvalumab + FLOT (n=74) | Placebo + FLOT (n=74) |
|---|---|---|
| Started Treatment | 100% | 99% |
| Finished FLOT | 96% | 95% |
| Tried Surgery | 91% | 90% |
| Complete Resection | 92% | 94% |
| Got Post-Surgery Treatment | 77% | 74% |
Moreover, safety data shows 95% of patients had side effects in both groups, with severe effects (grade 3/4) at 60-59%. Common issues like rash or tiredness were managed with steroids.
Handling Side Effects and Challenges
FLOT chemotherapy is tough, so patients need good health. Immunotherapy adds risks like tiredness or skin issues. However, Dr. Iqbal reassures, โThe studies have actually shown that itโs fairly well tolerated,โ with steroids helping control side effects. For example, managing these side effects is crucial in successful gastric cancer immunotherapy treatment.
Additionally, 15-20% of HER2+ cancers lose HER2 after initial treatment (T-ACT, GATHER studies), so re-testing is vital. Other options like CAR-T (CT01) improve survival (2.5 vs. 1.7 months; HR 0.36) but are costly and complex. Meanwhile, lenvatinib plus pembrolizumab boosts progress-free survival in some patients but doesnโt extend overall life, highlighting the need for careful patient selection.
Future Hope for Patients
Looking ahead, Dr. Iqbal sees a bright future with trials exploring new targets like CLDN18.2. Nivolumab remains a standard for some patients, and T-DXd helps HER2+ cases. Thus, testing biomarkers ensures the best care in ongoing gastric cancer immunotherapy developments.
Watch Dr. Iqbalโs full interview on OncologyTube to see her slides. For more, check our ASCO 2025 updates or visit USC Keck Medicine for care options.