FDA OKs New Treatment Option for Previously-Treated HER2-Positive Breast Cancer


Fam-trastuzumab deruxtecan-nxki (Enhertu, Daiichi Sankyo and AstraZeneca) is a new treatment option for patients with HER2-positive breast cancer who have progressed after 2 or more prior regimens.

FDA approved

Officials with the FDA have granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu, Daiichi Sankyo and AstraZeneca) for the treatment of adults with unresectable or metastatic human epidermal growth factor receptor (HER)2-positive breast cancer who have received 2 or more prior anti-HER2-based regimens in the metastatic setting, according to a press release.1,2

HER2-positive breast cancers are an aggressive type of breast cancer. Approximately 1 in 5 breast cancers have a gene mutation in the cancer cells that makes an excess of the HER2 protein, according to the FDA.1

Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody and topoisomerase inhibitor conjugate that targets the changes HER2 that help cancer grow, divide, and spread, and is linked to a topoisomerase inhibitor, which is a chemical compound that is toxic to cancer cells.1

“There have been many advances in the development of drugs for HER2-positive breast cancer since the introduction of Herceptin (trastuzumab) in 1998. The approval of Enhertu represents the newest treatment option for patients who have progressed on available HER2-directed therapies,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.1 “Drug development in the area of targeted therapies builds on our scientific understanding of malignant diseases not only in breast cancer, but in multiple other diseases.”

The approval is based on tumor response rate and duration of response observed in the phase 2 DESTINY-Breast01 clinical trial. The study, which included 184 female patients, evaluated fam-trastuzumab deruxtecan-nxki (5.4 mg/kg) as a monotherapy in HER2-positive breast cancer. Patients enrolled in the study received a median of 5 prior regimens in the locally advanced/metastatic setting. All patients received prior trastuzumab, ado-trastuzumab emtansine, and 66% had prior pertuzumab.2

According to the results, fam-trastuzumab deruxtecan-nxki demonstrated an objective response rate (ORR) of 60.3% (n=111; 95% CI: 52.9-67.4), including a 4.3% complete response rate and a 56% partial response rate.2

The study also showed a median duration of response of 11.4 months (95% CI: 13.8-16.9), which was demonstrated as of August 1, 2019. Recent data, which was reported at the San Antonio Breast Cancer Symposium, demonstrated a median progression-free survival of 16.4 months (95% CI: 12.7-Not Estimable), based on a median follow-up of 11.1 months.2

Regarding safety, fam-trastuzumab deruxtecan-nxki is approved with a Boxed Warning for interstitial lung disease (ILD)/pneumonitis and embryo-fetal toxicity. Safety was evaluated in a pooled analysis of 234 patients who received at least 1 dose of fam-trastuzumab deruxtecan-nxki in the DESTINY-Breast01 study and a phase 1 trial. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients.2

Management may require dose modification or treatment discontinuation and steroid treatment, according to Daiichi Sankyo. Overall, the most common adverse reactions were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, neutropenia, diarrhea, leukopenia, cough, and thrombocytopenia.2

“Once patients with HER2-positive metastatic breast cancer progress following at least 2 HER2 targeted regimens in the metastatic setting, there are limited treatment options,” Shanu Modi, MD, Breast Medical Oncologist, Memorial Sloan Kettering Cancer Center, said in a statement.2 “Enhertu has the potential to become a new standard of care.”

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Fam-trastuzumab deruxtecan-nxki will be available by prescription in the United States within the coming weeks, according to the release.2


1. FDA approves new treatment option for patients with HER2-positive breast cancer who have progressed on available therapies [news release]. FDA’s website. https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-option-patients-her2-positive-breast-cancer-who-have-progressed-available. Accessed December 23, 2019.
2. Enhertu Approved in the US for HER2 Positive Unresectable or Metastatic Breast Cancer Following Two or More Prior Anti-HER2-Based Regimens [news release]. Daiichi Sankyo’s website. https://www.daiichisankyo.com/media_investors/media_relations/press_releases/detail/007088.html. Accessed December 23, 2019.

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