The U.S. Food and Drug Administration (FDA) granted accelerated approval to trastuzumab deruxtecan for the treatment of adults with unresectable (unable to be removed with surgery) or metastatic (when cancer cells spread to other parts of the body) HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

Trastuzumab deruxtecan is a human epidermal growth factor receptor 2 (HER2)-directed antibody and topoisomerase inhibitor conjugate, meaning that the drug targets the changes in HER2 that help the cancer grow, divide and spread, and is linked to a topoisomerise inhibitor, which is a chemical compound that is toxic to cancer cells.

“There have been many advances in the development of drugs for HER2-positive breast cancer since the introduction of trastuzumab in 1998. The approval of trastuzumab deruxtecan represents the newest treatment option for patients who have progressed on available HER2-directed therapies,” said 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. “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.”

HER2-positive breast cancer is a type of breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells.

Approximately one of every five breast cancers have a gene mutation in the cancer cells that makes an excess of the HER2 protein.

HER2-positive breast cancers are an aggressive type of breast cancer.

Trastuzumab deruxtecan’s approval was based on the results of the phase II DESTINY-Breast01 trial trial enrolling 184 female patients with HER2-positive, unresectable and/or metastatic breast cancer who had received two or more prior anti-HER2 therapies in the metastatic setting.

These patients were heavily pretreated in the metastatic setting, receiving between two and 17 therapies prior to receiving trastuzumab deruxtecan.

Patients in the clinical trial received trastuzumab deruxtecan every three weeks and tumor imagining was obtained every six weeks.

The overall response rate was 60.3%, which reflects the percentage of patients that had a certain amount of tumor shrinkage with a median duration of response of 14.8 months.

The prescribing information for trastuzumab deruxtecan includes a Boxed Warning to advise health care professionals and patients about the risk of interstitial lung disease (a group of lung conditions that causes scarring of lung tissues) and embryo-fetal toxicity.

Interstitial lung disease and pneumonitis (inflammation of lung tissue), including cases resulting in death, have been reported with trastuzumab deruxtecan.

Health care professionals should monitor for and promptly investigate signs and symptoms including cough, dyspnea (difficult or labored breathing), fever and other new or worsening respiratory symptoms.

If these symptoms arise, trastuzumab deruxtecan may need to be withheld, the dose reduced or permanently discontinued.

Women who are pregnant should not take trastuzumab deruxtecan because it may cause harm to a developing foetus or newborn baby, or cause delivery complications.

The FDA advises health care professionals to tell females of reproductive age, and males with a female partner of reproductive potential, to use effective contraception during treatment with trastuzumab deruxtecan.

The most common side effects for patients taking trastuzumab deruxtecan were nausea, fatigue, vomiting, alopecia (hair loss), constipation, decreased appetite, anaemia (haemoglobin in blood is below the reference range), decreased neutrophil count (white blood cells that help lead your body’s immune system response to fight infection), diarrhoea, leukopenia (other white blood cells that help the immune system), cough and decreased platelet count (component of blood whose function is to react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot).

Decreased neutrophil count is a potentially serious and common side effect as described in the Medication Guide.

Patients treated with trastuzumab deruxtecan may be at increased risk of developing left ventricular dysfunction, which occurs when the heart is unable to pump blood effectively to the body, as this has been seen with other HER2-directed therapies for breast cancer.

Source: The Food and Drug Administration (FDA)

Watch our interview with Dr Ian Krop at SABCS 2019 about the DESTINY-Breast01 study here. 

Watch the press conference here.