Another Targeted Therapy for ERBB2-Positive Breast Cancer | Breast Cancer | JAMA | JAMA Network
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News From the Food and Drug Administration
February 4, 2020

Another Targeted Therapy for ERBB2-Positive Breast Cancer

JAMA. 2020;323(5):408. doi:10.1001/jama.2020.0222

The FDA recently granted accelerated approval to an antibody-drug combination for adults who’ve already received at least 2 treatment regimens for unresectable or metastatic breast cancer that is positive for human epidermal growth factor receptor 2 (ERBB2; formerly HER2/neu).

Marketed as Enhertu, fam-trastuzumab deruxtecan-nxki is an anti-ERBB2 antibody with a cytotoxic topoisomerase I inhibitor attached. It is administered via intravenous infusion. According to the FDA, about 20% of breast cancers have a genetic mutation that results in ERBB2-positive tumors, which are very aggressive.

The newly approved drug was evaluated in a 2-part phase 2 clinical trial to establish a recommended dose (5.4 mg/kg) and to assess safety and efficacy. Trial participants included 184 women whose previous treatment involved another antibody-drug conjugate, trastuzumab emtansine, which is standard second-line therapy for ERBB2-positive breast cancer. The investigators noted that if patients develop trastuzumab emtansine resistance, there’s no uniform agreement on which treatment to use next.

Among women in the trial who received the recommended dose of fam-trastuzumab deruxtecan-nxki, the overall response rate was 60.9% and treatment response lasted for a median of 14.8 months. The median progression-free survival was 16.4 months.

The investigators noted that results from their study appeared to substantially exceed those of currently available anti-ERBB2 treatments as well as new agents being developed. They pointed out that compared with trastuzumab emtansine, fam-trastuzumab deruxtecan-nxki has a higher concentration of drug relative to antibody. It’s also more likely than trastuzumab emtansine to kill adjacent tumor cells that don’t express the ERBB2 protein, and its short half-life reduces potential toxicity to healthy tissue.

However, the drug carries a boxed warning about the risk of developing interstitial lung disease and pneumonitis, which have caused deaths. The warning advises physicians to monitor for signs and symptoms including cough, dyspnea, fever, and other respiratory symptoms.