Trastuzumab deruxtecan
Trastuzumab deruxtecan, sold under the brand name Enhertu, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the topoisomerase I inhibitor deruxtecan (a derivative of exatecan). It is licensed for the treatment of breast cancer or gastric or gastroesophageal adenocarcinoma. Trastuzumab binds to and blocks signaling through epidermal growth factor receptor 2 (HER2/neu) on cancers that rely on it for growth. Additionally, once bound to HER2 receptors, the antibody is internalized by the cell, carrying the bound deruxtecan along with it, where it interferes with the cell's ability to  make DNA structural changes and replicate its DNA during cell division, leading to DNA damage when the cell attempts to replicate itself, destroying the cell. It was approved for medical use in the United States in December 2019, in Japan in March 2020, in the European Union in January 2021, and in Australia in October 2021. Medical uses. Trastuzumab deruxtecan-nxki is indicated 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 and for adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen. Side effects and label warnings. The most common side effects are nausea, fatigue, vomiting, alopecia (hair loss), constipation, decreased appetite, anemia (hemoglobin 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), diarrhea, 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). The prescribing information for fam-trastuzumab deruxtecan-nxki 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, including cases resulting in death, have been reported with fam-trastuzumab deruxtecan-nxki. History. The U.S. Food and Drug Administration (FDA) approved fam-trastuzumab deruxtecan-nxki in December 2019. The application for fam-trastuzumab deruxtecan-nxki was granted accelerated approval , fast track designation, and breakthrough therapy designation. The FDA approved fam-trastuzumab deruxtecan-nxki based on the results of one clinical 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 fam-trastuzumab deruxtecan-nxki. Patients in the clinical trial received fam-trastuzumab deruxtecan-nxki every three weeks and tumor imaging was obtained every six weeks. The overall response rate was 60.3%, which reflects the  percentage of patients who had a certain amount of tumor shrinkage with a median duration of response of 14.8 months. The FDA granted the approval of Enhertu to Daiichi Sankyo. On 10 December 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Enhertu, intended for the treatment of metastatic HER2-positive breast cancer. Enhertu was reviewed under EMA's accelerated assessment program. The applicant for this medicinal product is Daiichi Sankyo Europe GmbH. Trastuzumab deruxtecan was approved  for medical use in the European Union in January 2021. In January 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to fam-trastuzumab deruxtecan-nxki for the treatment of adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen. Efficacy was evaluated in a multicenter, open-label, randomized trial (DESTINY-Gastric01, NCT03329690) in participants with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma who had progressed on at least two prior regimens, including trastuzumab, a fluoropyrimidine- and a platinum-containing chemotherapy. A total of  188 participants were randomized (2:1) to receive fam-trastuzumab deruxtecan-nxki 6.4 mg/kg intravenously every three weeks or physician’s choice of either irinotecan or paclitaxel monotherapy.