The Food and Drug Administration (FDA) has granted accelerated approval to Enhertu (fam-trastuzumab deruxtecan-nxki; AstraZeneca and Daiichi Sankyo) for the treatment of adults with unresectable or metastatic HER2-positive breast cancer who have received 2 or more prior anti-HER2-based regimens in the metastatic setting. 

The approval was based on results from the phase 2, open-label, single-group, multicenter DESTINY-Breast01 trial that included 184 female patients with HER2-positive, unresectable and/or metastatic breast cancer who had received ≥2 prior anti-HER2 therapies. Patients received Enhertu 5.4mg/kg by intravenous (IV) infusion every 3 weeks until unacceptable toxicity or disease progression. The primary end point was the objective response rate (ORR) per imaging assessment obtained every 6 weeks; a key secondary end point included the duration of response (DOR).

Results showed a confirmed ORR of 60.3% (n=111; 95% CI: 52.9, 67.4) including a 4.3% complete response rate (n=8) and a 56.0% partial response rate (n=103), and a median DOR of 14.8 months (95% CI: 13.8, 16.9). Additional study data, recently presented at the San Antonio Breast Cancer Symposium and published online in The New England Journal of Medicine, showed a median progression-free survival of 16.4 months (95% CI: 12.7-not estimable) based upon a median duration of follow up of 11.1 months.

Regarding safety, Enhertu carries a Boxed Warning for interstitial lung disease and embryo-fetal toxicity. The most common adverse reactions associated with treatment included nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, neutropenia, diarrhea, leukopenia, cough and thrombocytopenia. 

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José Baselga, Executive VP, Oncology R&D, said: “Enhertu has shown impressive results in women with HER2-positive metastatic breast cancer, with the majority of women benefiting from treatment and the median duration of the response exceeding 14 months. With this first approval, we are proud to bring Enhertu to patients with high unmet need and we look forward to further exploring its potential in additional settings.”

Enhertu, a HER2-directed antibody and topoisomerase inhibitor conjugate, was previously granted Priority Review, Breakthrough Therapy and Fast Track designations by the FDA. The product will be available within the coming weeks as 100mg single-dose vials.

For more information visit enhertu.com.