FDA recently granted accelerated approval to Enhertu (fam-trastuzumab deruxtecan-nxki) for the treatment of adults with metastatic or unresectable (unable to be removed surgery) HER2-positive breast cancer. The treatment is, however, only for patients who have received two or more anti-HER2-based regiments in the metastatic setting beforehand.
HER2-positive breast cancer is a specific type of breast cancer that tests positive for human epidermal growth factor receptor 2 (HER2) – a protein that promotes the growth of cancer cells. One out of 5 breast cancers develops a mutation that leads to excessive production of the HER2 protein. This type of breast cancer is more aggressive and less likely to be sensitive to hormone therapy.
Experts recommend that every invasive breast cancer should be tested for HER2 as the treatment procedure is different for the ones that test negative for the gene. Furthermore, as cancer recurs or spreads, the cells should be retested given that the status can change from the original diagnosis.
Enhertu is an HER2 directed antibody and topoisomerase inhibitor conjugate that targets and restricts the gene and also promotes the production of a compound that is toxic to cancer cells.
According to Richard Pazdur, M.D., 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, “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”. He further added, “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.”
Enhertu’s approval came after an extensive clinical trial that involved 184 females with metastasized or HER2 positive breast cancer who had received two or more anti-HER2 therapies beforehand. The patients were previously treated with 2 to 17 therapies in the metastatic setting.
The subjects received Enhertu every three weeks and tumor imaging was obtained every six weeks. With a median duration of response of 14.8 months, 60.3 % of patients showed a certain extent of tumor shrinkage.
The prescription box for the drug comes with a boxed warning, giving details about the risks of usage – which may cause interstitial lung disease, a group of lung conditions that cause scarring of the tissues. Furthermore, it might also cause embryo-fetal toxicity and eventually death.
If symptoms including cough, dyspnea, fever, and worsening respiratory conditions begin to arise post drug usage, Enhertu might need to be withheld, dosage reduced or permanently discontinued.
Enhertu was granted Accelerated Approval, which enables the FDA to approve drugs ‘for serious conditions to fill an unmet medical need’. It is given based on a more easily obtained data that predicts long term benefits.
The application was given Breakthrough Therapy designation that expedites the development and review of drugs intended to treat a serious condition when preliminary clinical trials indicate that the drug may demonstrate considerable improvement over available therapies.
About the U.S. Food and Drug Administration (FDA)
FDA is an agency within the US Department of Health and Human Services that is responsible for protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, vaccines and medical devices. The agency also overlooks the safety and security of the nation’s food supply, cosmetics, and dietary supplements.