Fam-trastuzumab deruxtecan-nxki extends survival in HER2-low metastatic breast cancer
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Fam-trastuzumab deruxtecan-nxki improved outcomes among patients with HER2-low unresectable or metastatic breast cancer, according to topline data released by the agent’s manufacturer.
The agent extended PFS and OS compared with physician’s choice of chemotherapy regardless of patients’ hormone receptor status, results of the randomized phase 3 DESTINY-Breast04 trial showed.
“[This] historic news from DESTINY-Breast04 could reshape how breast cancer is classified and treated,” Susan Galbraith, PhD, executive vice president for oncology research and development with AstraZeneca, said in a company-issued press release. “A HER2-directed therapy has never before shown a benefit [for] patients with HER2-low metastatic breast cancer. These results for Enhertu are a huge step forward and could potentially expand our ability to target the full spectrum of HER2 expression, validating the need to change the way we categorize and treat breast cancer.”
Fam-trastuzumab deruxtecan-nxki (Enhertu; AstraZeneca, Daiichi Sankyo), a HER2-directed antibody-drug conjugate, 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. It also is approved for treatment of adults with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma who received a prior trastuzumab (Herceptin, Genentech)-based regimen.
The global, open-label DESTINY-Breast04 trial 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.
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.
Rates of interstitial lung disease appeared consistent with those observed in late-line HER2-positive breast cancer trials of fam-trastuzumab deruxtecan-nxki.
Complete results of DESTINY-Breast04 will be submitted for presentation at a medical meeting.
“DESTINY-Breast04 is the first ever phase 3 trial of a HER2-directed therapy in patients with HER2-low metastatic breast cancer to show statistically significant and clinically meaningful benefit in progression-free and overall survival compared [with] standard treatment,” Ken Takeshita, MD, global head for research and development with Daiichi Sankyo, said in the release. “We look forward to sharing the detailed findings of DESTINY-Breast04 with the medical community and initiating discussions with regulatory agencies globally with the goal of bringing Enhertu to patients with metastatic breast cancer previously considered to be HER2-negative.”
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