Enhertu Achieves Breakthrough in Stomach Cancer Treatment, Expanding Its Indications

AstraZeneca and Daiichi Sankyo's antibody-drug conjugate Enhertu has marked a significant milestone in the treatment of stomach cancer, becoming the first HER2-directed medicine to demonstrate improved overall survival in a randomized Phase III trial for second-line metastatic gastric cancer patients.

Phase III Trial Success

The Destiny-Gastric04 study, which evaluated Enhertu as a second-line therapy for HER2-positive unresectable and/or metastatic gastric or gastroesophageal junction cancer, showed a "statistically significant and clinically meaningful improvement" in overall survival compared to the combination of ramucirumab and paclitaxel. This breakthrough led an independent data monitoring committee to recommend unblinding the trial ahead of schedule, underscoring the drug's potential efficacy.

Ken Takeshita, global head of Oncology R&D at Daiichi Sankyo, emphasized the significance of this achievement, stating, "Enhertu is the first HER2 directed medicine to demonstrate an improvement in overall survival in a randomized phase 3 trial in the second-line metastatic setting of patients with HER2 positive gastric cancer."

Expanding Indications and Regulatory Implications

Enhertu, which targets the HER2 protein and carries a topoisomerase I inhibitor payload, has been steadily expanding its list of indications since its initial approval in 2019. The drug is currently approved for various types of breast, lung, and gastric cancers in over 65 countries.

The partners plan to leverage the Destiny-Gastric04 results to seek approvals in regions where Enhertu is not currently indicated as a second-line option for gastric and gastroesophageal junction cancer. Additionally, they aim to secure full approval in areas where the drug is only conditionally approved.

This latest success builds on Enhertu's previous achievements, including its January 2021 accelerated FDA approval for gastric or gastroesophageal junction cancers based on Phase II data. The drug has also made history by pioneering the HER2-low breast cancer category and recently received FDA approval for HER2-ultralow disease.

Future Prospects and Ongoing Research

As AstraZeneca and Daiichi Sankyo continue to expand Enhertu's potential, they have launched the four-arm Phase III Destiny-Gastric05 trial to test the drug as a first-line treatment for HER2-positive stomach cancer. This study, with a primary completion date set for 2028, demonstrates the partners' commitment to further advancing Enhertu's capabilities in gastric cancer treatment.

The success of Enhertu in the challenging field of stomach cancer treatment is particularly noteworthy, given the historical difficulties researchers have faced in this area. As the pharmaceutical industry continues to evolve, Enhertu's achievements represent a significant step forward in the ongoing battle against various forms of cancer.