Over the past year (December 2019–September 2020), the U.S. Food and Drug Administration (FDA) granted approval to several novel drugs and new indications for therapeutic agents used in breast cancer.
On June 29, 2020, the FDA approved a new fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase–zzxf (Phesgo) for subcutaneous injection for the following indications1,2:
Use in combination with chemotherapy as neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer as part of a complete treatment regimen for early breast cancer; and as adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence;
Use in combination with docetaxel for treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.
Approval was based on findings in the open-label, multicenter FeDeriCa trial (ClinicalTrials.gov identifier NCT03493854).2
On April 17, 2020, tucatinib (Tukysa) was approved for use in combination with trastuzumab and capecitabine for treatment of adults with advanced unresectable or metastatic HER2-positive breast cancer. These included patients with brain metastases and those who have received one or more prior anti-HER2 regimens in the metastatic setting.
Approval was based on findings from the phase III HER2CLIMB trial (NCT02614794). See pages 16 and34 for more on the trial.
Tucatinib has warnings/precautions for diarrhea, hepatotoxicity, and embryofetal toxicity. Severe diarrhea has been reported, as well as severe hepatotoxicity.
On February 25, 2020, neratinib (Nerlynx) was approved for use in combination with capecitabine for treatment of advanced or metastatic HER2-positive breast cancer in patients who have received two or more prior anti-HER2–based regimens in the metastatic setting.
The current approval was based on findings from the open-label phase III NALA trial (NCT01808573).
On December 20, 2019, the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki (Enhertu) was granted accelerated approval in the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2–based regimens in the metastatic setting.
Accelerated approval was based on the response rate and duration in the multicenter phase II DESTINY-Breast01 trial (NCT03248492).
Fam-trastuzumab deruxtecan has a boxed warning for interstitial lung disease and embryofetal toxicity.
1. U.S. Food and Drug Administration: FDA approves pertuzumab/trastuzumab/hyaluronidase-zzxf in combination for treatment of adults with HER2-positive breast cancer. Available at www.fda.gov. Accessed July 7, 2020.
2. Phesgo (pertuzumab, trastuzumab, and hyaluronidase-zzxf) injection, for subcutaneous use, prescribing information, Genentech, Inc, June 2020. More information available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761170s000lbl.pdf. Accessed July 7, 2020.