On May 4, 2022, the FDA granted a regular full approval for fam-trastuzumab deruxtecan-nxki (Enhertu; Daiichi Sankyo) for adults with unresectable or metastatic HER2-positive breast cancer who had previously received an anti-HER2 regimen in the metastatic or the neoadjuvant or adjuvant setting whose disease recurred during or within 6 months of completing therapy, based on the confirmatory DESTINY-Breast03 clinical trial.
“Enhertu has demonstrated significant progression-free survival in the earlier metastatic setting, potentially establishing it as a new standard of care in previously treated patients with HER2-positive metastatic breast cancer. Today’s approval is an important milestone for the clinical community as we will now be able to offer Enhertu to these patients earlier in their treatment,” said Erika Hamilton, MD, Director of the Breast Cancer and Gynecological Cancer Research Program, Sarah Cannon Research Institute, Nashville, TN, in a press release.
This regular approval was based on the results of the confirmatory clinical trial DESTINY-Breast03 conducted after the December 2019 FDA accelerated approval for fam-trastuzumab deruxtecan for adults with unresectable or metastatic HER2-positive breast cancer who have received ≥2 anti-HER2 regimens in the metastatic setting.
The DESTINY-Breast03 study was a multicenter, open-label, randomized clinical trial of 524 patients with HER2-positive, unresectable, and/or metastatic breast cancer who had received trastuzumab and taxane therapy for metastatic disease or whose disease recurred during or within 6 months of completing neoadjuvant or adjuvant therapy. Patients were randomized (1:1) to intravenous fam-trastuzumab deruxtecan or to ado-trastuzumab emtansine every 3 weeks, until disease progression or unacceptable adverse events.
The main efficacy outcome measure was progression-free survival (PFS). Key secondary end points were overall survival (OS) and confirmed objective response rate (ORR). The median PFS was not reached (95% confidence interval [CI], 18.5-not estimable) in the fam-trastuzumab deruxtecan arm and was 6.8 months (95% CI, 5.6-8.2) in the ado-trastuzumab emtansine arm. The hazard ratio was 0.28 (95% CI, 0.22-0.37; P <.0001). At the time of the PFS analysis, 16% of patients had died and the OS was immature. The ORR was 82.7% (95% CI, 77.4-87.2) and 36.1% (95% CI, 30.0-42.5), respectively.
The most common (incidence >30%) adverse reactions with fam-trastuzumab deruxtecan were nausea, fatigue, vomiting, alopecia, constipation, anemia, and musculoskeletal pain. Serious adverse reactions in >1% of patients with this drug were vomiting, interstitial lung disease, pneumonia, pyrexia, and urinary tract infection. The prescribing information of fam-trastuzumab deruxtecan includes a warning about the risk for interstitial lung disease and embryo-fetal toxicity.