FDA grants priority review to Enhertu for HER2-low metastatic breast cancer
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The FDA granted priority review to fam-trastuzumab deruxtecan-nxki for treatment of certain patients with HER2-low breast cancer.
The designation applies to adults with unresectable or metastatic disease who received prior therapy in the metastatic setting.
Fam-trastuzumab deruxtecan-nxki (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 is approved in the United States for treatment of certain patients with unresectable or metastatic HER2-positive breast cancer who received a prior anti-HER2-based regimen. It also is approved for treatment of patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who received a prior trastuzumab-based regimen.
The FDA based the priority review on results of the DESTINY-Breast04 study, presented at this year’s ASCO Annual Meeting and published simultaneously in The New England Journal of Medicine.
The study included 557 patients with HER2-low metastatic breast cancer who previously received one or two prior lines of chemotherapy for metastatic disease.
Researchers randomly assigned patients 2:1 to 5.4 mg/kg fam-trastuzumab deruxtecan-nxki (n = 373) or physician’s choice of chemotherapy (n = 184), including capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel (Abraxane, Bristol Myers Squibb).
PFS by blinded independent central review among those with hormone receptor-positive disease served as the primary endpoint. PFS by blinded independent central review among all randomly assigned patients, OS among those with hormone receptor-positive disease and OS among all randomly assigned patients served as secondary outcomes. Other endpoints included objective response rate, duration of response, safety and an exploratory analysis of patients with hormone receptor-negative metastatic breast cancer.
Median follow-up was 18.4 months.
As Healio previously reported, results showed longer median PFS (9.9 months vs. 5.1 months; HR = 0.5; 95% CI, 0.4-0.63) and OS (23.4 months vs. 16.8 months; HR = 0.64; 95% CI, 0.49-0.84) among patients assigned fam-trastuzumab deruxtecan-nxki.
The agent exhibited a safety profile consistent with that observed in prior clinical trials.
“For more than 2 decades, only patients with HER2-positive breast cancer have been able to benefit from HER2-targeted therapies,” Susan Galbraith, executive vice president for oncology research and development with AstraZeneca, said in the release. “If approved, Enhertu will redefine how we classify and treat metastatic breast cancer, enabling patients whose tumors have lower levels of HER2 expression the opportunity to benefit from a HER2-directed therapy.”
The FDA is expected to make a decision on approval for this indication in the fourth quarter of this year.
The agency previously granted breakthrough therapy designation to fam-trastuzumab deruxtecan-nxki for treatment of metastatic HER2-low breast cancer.
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