Enhertu receives breakthrough therapy designation for breast cancer subset
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The FDA granted breakthrough therapy designation to fam-trastuzumab deruxtecan-nxki for treatment of adults with unresectable or metastatic HER2-low breast cancer, according to a press release from the agent’s manufacturer.
The designation applies to use of the HER2-directed antibody-drug conjugate by patients who previously received a systemic therapy in the metastatic setting or experienced disease recurrence during or within 6 months of adjuvant chemotherapy. Those with hormone receptor-positive disease also should have received or not be eligible for endocrine therapy.
Fam-trastuzumab deruxtecan-nxki (Enhertu; AstraZeneca, Daiichi Sankyo) is approved in the United States for treatment of adults with unresectable or metastatic HER2-positive breast cancer who received two or more prior anti-HER2-based regimens in the metastatic setting. It also is approved for treatment of adults with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who received a prior trastuzumab-based regimen.
The breakthrough therapy designation is based on results of the randomized phase 3 DESTINY-Breast04 trial, which included 540 patients from North America, Europe or Asia with hormone receptor-positive (n = 480) or hormone receptor-negative (n = 60) unresectable or metastatic breast cancer who received up to two prior lines of chemotherapy.
All patients had centrally confirmed HER2-low status defined as an immunohistochemistry score of 1+ or 2+, with a negative in-situ hybridization score.
Researchers randomly assigned patients to 2:1 to 5.4 mg/kg fam-trastuzumab deruxtecan-nxki or physician’s choice of chemotherapy, which included capecitabine, eribulin, gemcitabine, paclitaxel or nab-paclitaxel.
PFS by blinded independent central review among patients with hormone receptor-positive disease served as the primary endpoint. Key secondary endpoints included PFS by blinded independent central review among all randomly assigned patients, OS among patients with hormone receptor-positive disease, and OS among all randomly assigned patients. Other endpoints included PFS, duration of response and safety.
As Healio previously reported, the trial met its primary endpoint, as researchers observed significantly longer PFS among patients with hormone receptor-positive disease assigned fam-trastuzumab deruxtecan-nxki. Researchers also reported longer PFS with fam-trastuzumab deruxtecan-nxki among patients regardless of hormone receptor status, longer OS among patients with hormone receptor-positive disease and longer OS among all randomly assigned patients.
Fam-trastuzumab deruxtecan-nxki exhibited a safety profile consistent with that observed in prior trials. Investigators identified no new safety concerns.
“Historically, only patients with HER2-positive metastatic breast cancer were shown to benefit from HER2-directed therapy,” Ken Takeshita, MD, global head of research and development for Daiichi Sankyo, said in the press release. “DESTINY-Breast04 ... is the first trial to demonstrate that selecting patients for treatment based on low expression of HER2 has the potential to change the diagnostic and treatment paradigms for these patients.”
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