Enhertu Strengthens Position in Gastric Cancer Treatment with Positive ASCO Data

AstraZeneca and Daiichi Sankyo's targeted cancer medicine Enhertu has demonstrated superior efficacy in treating advanced gastric cancer, according to data presented at the American Society of Clinical Oncology's (ASCO) annual meeting. The findings from the Destiny-Gastric04 trial solidify Enhertu's growing role in stomach cancer care and provide physicians with a clearer second-line treatment option for patients with HER2-positive gastric cancer.

Enhertu Outperforms Standard Treatment in Phase 3 Trial

In the late-stage clinical trial, Enhertu extended overall survival by 30% compared to a widely used regimen of Eli Lilly's Cyramza plus chemotherapy. Patients treated with Enhertu achieved a median survival of 14.7 months, compared to 11.4 months for those receiving the Cyramza-chemotherapy combination. The antibody-drug conjugate also reduced the risk of disease progression by 26%, delaying relapse or death by 1.1 months.

The trial enrolled nearly 500 participants with HER2-positive gastric cancer who had progressed after initial treatment with Herceptin. Enhertu demonstrated superior efficacy across multiple endpoints, with 44% of Enhertu-treated patients experiencing tumor shrinkage or disappearance, compared to 29% in the Cyramza-chemotherapy group.

Implications for Clinical Practice and Market Position

Dr. Pamela Kunz, a Yale University specialist in gastrointestinal cancer, commented on the study's significance: "This study is practice-validating in the U.S., given [Enhertu's] existing inclusion in guidelines and current use in the second-line setting. It will be practice-changing in many countries outside of the U.S., and will really position [Enhertu] as a preferred second-line treatment."

The findings are expected to reinforce AstraZeneca and Daiichi Sankyo's market position in the gastric cancer space. Enhertu, which combines the active agent in Herceptin with a chemotherapy toxin, has already received FDA approval for HER2-positive gastric cancer following first-line treatment with Herceptin. The drug is one of AstraZeneca's six blockbuster cancer drugs and its fastest-growing oncology product, generating over $3 billion in revenue in 2024.

Safety Considerations and Future Directions

While Enhertu demonstrated superior efficacy, the trial also highlighted important safety considerations. Nearly all participants experienced side effects, with a slightly higher incidence in the Enhertu group (93%) compared to the Cyramza-chemotherapy group (91%). Notably, 14% of patients treated with Enhertu experienced inflammation or scarring of lung tissue, a known side effect that has previously prompted the FDA to issue a "black box" warning on the drug's label.

Dr. Kunz emphasized the importance of careful patient selection, stating that physicians should "take note" of the lung damage incidence and "think about patient selection and consider patient comorbidities" before prescribing Enhertu.

Looking ahead, AstraZeneca and Daiichi Sankyo are working to expand Enhertu's use further by testing it in newly diagnosed patients with inoperable HER2-positive tumors. The ongoing Destiny-Gastric05 trial is evaluating Enhertu in combination with Merck & Co.'s immunotherapy Keytruda and chemotherapy, compared to the FDA-approved regimen of Herceptin, Keytruda, and chemotherapy. Results from this trial are expected in approximately three years, potentially paving the way for Enhertu's use in first-line treatment of advanced gastric cancer.