Enhertu Receives Second FDA Breakthrough Therapy Designation for HER2-Positive Metastatic Gastric Cancer

Text | Baihuawen

On May 11, AstraZeneca and Daiichi Sankyo announced that Enhertu (trastuzumab deruxtecan) had been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with HER2-positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who have previously received at least two prior regimens, including trastuzumab. Daiichi Sankyo had already submitted a marketing application in Japan for this indication on May 7.

This is the second Breakthrough Therapy Designation granted by the FDA to Enhertu. In 2017, the FDA first granted Enhertu Breakthrough Therapy Designation for the treatment of HER2+ metastatic breast cancer, an indicationApproved by the FDA in 2019.

The results of the Phase II DESTINY-Gastric01 study demonstrated that patients treated with the Enhertu plus chemotherapy combination regimen achieved significantly higher objective response rate (ORR) and overall survival (OS) compared to the chemotherapy-alone group, thereby meeting the primary and secondary endpoints of the trial. Specific trial data will be presented at the upcoming ASCO 2020.

The safety and tolerability profile was consistent with previous study results. The most common adverse events were hematologic and gastrointestinal reactions, including neutropenia, anemia, nausea, and decreased appetite. Most cases of drug-related interstitial lung disease and pneumonitis were Grade 1 and Grade 2, with two cases of Grade 3 and one case of Grade 4.

Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related deaths. In 2018, there were approximately 1 million new cases of gastric cancer diagnosed globally, with 783,000 deaths. It is estimated that in the United States in 2020, there will be 27,600 new cases of gastric cancer and 11,000 deaths.

Gastric cancer is often diagnosed at an advanced stage. Even with early diagnosis, patient survival rates remain moderate, while the 5-year survival rate for patients with metastatic gastric cancer is only 5%. Approximately one-fifth of gastric cancer patients are HER2-positive. Currently, the first-line treatment regimen for HER2-positive, advanced or metastatic gastric cancer is trastuzumab combined with chemotherapy. However, there are currently no approved HER2-targeted therapies for gastric cancer patients who progress after first-line treatment.

José Baselga, Vice President of Oncology R&D at AstraZeneca, stated, “Current treatment options are limited to patients with HER2-positive metastatic gastric cancer, and there are no approved HER2-targeted therapies for patients with recurrent disease. We look forward to collaborating with the FDA to further explore the potential of Enhertu as a significant new therapeutic option and the first antibody-drug conjugate for this important disease.”