Gastric Cancer

Investigators will present detailed results from the phase 3 FORTITUDE-101 trial at a future medical meeting.

Subgroup analyses from the phase 3 CheckMate649 and KEYNOTE-859 clinical trials showed little OS difference between investigational and chemotherapy arms.

Phase 2 data may support nivolumab plus low-dose ipilimumab as a promising option in patients with microsatellite instability–high gastric cancer.

Satri-cel led to a median PFS of 3.25 months vs 1.77 months with physician’s choice in patients with pretreated gastric or gastroesophageal cancer.

T-DXd improved OS, PFS, ORR, and DOR vs ramucirumab plus paclitaxel in the second-line treatment of HER2-positive gastric cancer or gastroesophageal junction adenocarcinoma.

Antitumor activity was observed in patients with gastroesophageal adenocarcinoma treated with the combination regardless of chemotherapy type.

The safety profile of TFOX was consistent with data reported in previous studies, and no new safety signals were identified.

Pathological complete response was higher among patients with ERBB2–positive gastric cancer or GEJ adenocarcinoma treated with atezolizumab vs without.

Results from the phase 2/3 trial also show a favorable OS trend for KN026 with chemotherapy vs placebo with chemotherapy in HER2-positive gastric cancer.

Nivolumab-based therapies showed improved efficacy vs chemotherapy in hypermutated and Epstein-Barr virus–positive gastroesophageal tumors.

Data from the phase 3 KEYNOTE-811 trial supported the FDA approval of this pembrolizumab combination in locally advanced unresectable or metastatic, PD-L1–positive, HER2-positive gastric or GEJ adenocarcinoma.

Phase 3 data support ramucirumab/paclitaxel switch maintenance as a post-induction therapy for patients who are not eligible for immunotherapy.

Data from the MATTERHORN trial show a trend towards improved overall survival with the durvalumab combination in gastric and GEJ cancers.

The safety profile of trastuzumab deruxtecan in the phase 3 DESTINY-Gastric04 trial was consistent with the established safety profile of the agent.

Panelists discuss how the long-term follow-up data from CheckMate649 are crucial for understanding the durability of nivolumab plus chemotherapy’s benefit in first-line advanced gastric cancers (GCs)/gastroesophageal junction cancers (GEJCs). The survival outcomes help validate this regimen’s position as a standard of care, particularly for patients with PD-L1 combined positive score (CPS) ≥ 5. Although the magnitude of benefit varies by PD-L1 expression, both overall survival (OS) and progression-free survival (PFS) data inform personalized treatment decisions, with stronger evidence supporting immunotherapy use in higher PD-L1–expressing tumors while maintaining use across most patient subgroups.

Panelists discuss how the CheckMate649 study was a randomized trial that compared nivolumab plus FOLFOX (leucovorin, fluorouracil, oxaliplatin) chemotherapy with chemotherapy alone for treating advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. The study results found that nivolumab plus chemotherapy improved overall survival and progression-free survival compared with chemotherapy alone.

Panelists discuss how advanced gastric cancer treatments currently include surgery, chemotherapy (primarily platinum/fluoropyrimidine combinations), targeted therapies (trastuzumab for HER2-positive disease, ramucirumab), and immunotherapy (pembrolizumab and nivolumab in select patients). Despite these options, major unmet needs persist, with low survival rates, lack of predictive biomarkers beyond HER2, limited effective treatments after first-line therapy, poor response rates to immunotherapy, and high treatment toxicity affecting quality of life. Many patients also present with late-stage disease due to delayed diagnosis.

Pembrolizumab plus lenvatinib showed a safety profile consistent with previous reports evaluating the combination.

John Marshall, MD, discussed zolbetuximab, which the FDA recently approved for patients with CLDN18.2–positive locally advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma.

Zolbetuximab’s targeted action, combined with manageable adverse effects, positions it as a promising therapy for advanced gastric cancer.

Additional genetic testing measures and targeted therapies may improve outcomes for patients with diverse molecular subgroups of gastric cancers.

Data from the SPOTLIGHT and GLOW trials reveal that zolbetuximab increased survival in patients with CLDN18.2-positive gastric or GEJ adenocarcinoma.

The incorporation of zolbetuximab in addition to chemotherapy has shown benefit in patients with Claudin 18.2–positive gastric cancers in clinical trials.

Data from the phase 3 SPOTLIGHT trial and the phase 3 GLOW trial supported the approval of zolbetuximab plus chemotherapy in this indication.

Data from the GLOW and SPOTLIGHT trials support the European Commission’s approval of zolbetuximab for patients with CLDN18.2-positive gastric cancer.

Second-line fruquintinib plus paclitaxel did not sustain sufficient efficacy for patients with advanced gastric or GEJ adenocarcinoma to support approval in China.

The addition of neoadjuvant S-1 also reduced the risk of death compared with adjuvant therapy alone in the phase 3 PRODIGY trial.

Enrollment will soon begin for the dose-expansion portion of the ongoing phase 1 trial assessing EO-3021 in CLDN18.2-positive tumors.

Combining evorpacept with trastuzumab, ramucirumab, and paclitaxel appeared to be well tolerated among patients enrolled on the phase 2 ASPEN-06 trial.

Frontline zolbetuximab plus chemotherapy is one step closer to approval by the European Commission for select patients with advanced gastric/GEJ cancer.