FDA expands Enhertu approval for breast cancer

In In The News by Barbara Jacoby

From: healio.com

The FDA expanded the approval of fam-trastuzumab deruxtecan to include treatment of patients with HER2-positive metastatic breast cancer who received a prior anti-HER2-based regimen.

Fam-trastuzumab deruxtecan (Enhertu; AstraZeneca, Daiichi Sankyo) is a novel antibody-drug conjugate with three components: a humanized anti-HER2 immunoglobulin G1 monoclonal antibody with the same amino acid sequence as trastuzumab (Herceptin, Genentech); a topoisomerase 1 inhibitor payload; and a tetrapeptide-based cleavable linker.

The agent already had been approved in the United States for treatment of adults with unresectable or metastatic HER2-positive breast cancer who had received two or more prior anti-HER2-based regimens, as well as for treatment of adults with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma who received a prior trastuzumab-based regimen.

The FDA based the new breast cancer indication on results of the randomized phase 3 DESTINY-Breast03 trial, which enrolled approximately 500 patients from North America, South America, Europe, Asia and Oceania. All patients had HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

Researchers compared fam-trastuzumab deruxtecan — dosed at 5.4 mg/kg — vs. the HER2-targeted antibody-drug conjugate ado-trastuzumab emtansine (Kadcyla, Genentech).

PFS assessed by blinded independent central review served as the primary efficacy endpoint.

As Healio previously reported, results showed fam-trastuzumab deruxtecan reduced risk for progression or death by 72% compared with ado-trastuzumab emtansine (HR = 0.28; 95% CI, 0.22-0.37).

Fam-trastuzumab deruxtecan exhibited a safety profile consistent with that observed in prior clinical trials. No grade 4 or grade 5 treatment-related interstitial lung disease events occurred.

“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,” Erika Hamilton, MD, director of the breast cancer and gynecologic cancer research program at Sarah Cannon Research Institute, said in an AstraZeneca-issued press release. “[This] 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.”