ASCO24: Enhertu doubles response in HER2-ultralow breast cancer

During a recent presentation at the American Society of Clinical Oncology (ASCO) annual meeting, AstraZeneca and Daiichi Sankyo shared encouraging results from their Phase III DESTINY-Breast06 trial. The study highlighted the benefits of their drug, Enhertu (trastuzumab deruxtecan), for breast cancer patients with HER2-low tumors. The trial data indicated that these patients had a 38% lower risk of cancer progression or metastasis when treated with Enhertu compared to chemotherapy.

Earlier in April, AstraZeneca and Daiichi Sankyo had teased preliminary findings showing that Enhertu significantly improved progression-free survival (PFS) among HR-positive patients with HER2-low or HER2-ultralow status. The detailed results unveiled on Sunday provided a clearer picture of the drug's performance in these subgroups, illustrating substantial survival and response benefits.

The DESTINY-Breast06 trial involved 866 breast cancer patients who had previously undergone at least one endocrine therapy treatment, and most had also received a CDK4/6 inhibitor. The participants were divided into two groups: 713 patients with HER2-low tumors and 153 with HER2-ultralow tumors. They were randomly assigned to receive either Enhertu or a chemotherapy regimen chosen by their doctors.

Results showed that patients with HER2-low tumors who received Enhertu achieved a median PFS of 13.2 months, in contrast to 8.1 months for those in the chemotherapy group. Similar outcomes were observed in the HER2-ultralow subgroup. These findings suggest that Enhertu could potentially alter the classification and treatment approach for metastatic breast cancer, noted lead author Giuseppe Curigliano. He emphasized that Enhertu could be used earlier in treating HR+ metastatic breast cancer and might benefit new patient groups who previously lacked targeted treatment options post-endocrine therapy.

Enhertu also demonstrated a higher objective response rate (ORR) compared to chemotherapy. In the HER2-low group, the ORR was 56.5% for Enhertu-treated patients versus 32.3% for those on chemotherapy. The results were even more pronounced in the HER2-ultralow group, with an ORR of 61.8% for Enhertu compared to 26.3% for chemotherapy.

However, the data also highlighted some concerns regarding toxicity. ASCO expert Erica Mayer commented that while Enhertu could become a preferred first-line treatment for most HR+ metastatic breast cancer patients following progression on endocrine therapy, the therapy's specific toxicities must be considered. The trial showed that Enhertu was associated with a higher rate of serious side effects—41% in the Enhertu group versus 31% in the chemotherapy group. Notably, 11% of Enhertu-treated patients experienced interstitial lung disease, which led to 5% discontinuing the treatment and resulted in three deaths.

Enhertu has already been approved in the US, EU, and other countries for treating unresectable or metastatic HER2-low breast cancer based on the positive outcomes from the Phase III DESTINY-Breast04 trial. The latest data from DESTINY-Breast06 further reinforces Enhertu's potential as a valuable treatment option for this patient population, albeit with a need for careful management of its associated toxicities.