Trastuzumab deruxtecan extends PFS in HER2-positive metastatic breast cancer
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Trastuzumab deruxtecan significantly prolonged PFS compared with ado-trastuzumab emtansine among patients with HER2-positive metastatic breast cancer, topline data of a randomized phase 3 trial showed.
Patients with HER2-positive metastatic breast cancer who undergo initial treatment with trastuzumab (Herceptin, Genentech) and a taxane often experience disease progression, so more effective options are necessary to extend survival.
Trastuzumab deruxtecan (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 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 open-label DESTINY-Breast03 trial 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 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. Secondary endpoints included OS, objective response rate, duration of response, clinical benefit rate, investigator-assessed PFS and safety.
At a planned interim analysis, the independent data monitoring committee determined the trial met its primary endpoint. The committee recommended unblinding based on these results.
“There is a continued need for new options and better outcomes for patients with HER2-positive metastatic breast cancer who often experience disease progression after initial treatment with available standards of care,” Susan Galbraith, executive vice president for oncology research and development for AstraZeneca, said in a company-issued press release. “These transformative progression-free survival results demonstrate the superiority of Enhertu compared [with ado-trastuzumab emtansine], and the encouraging safety data may open future opportunities to bring this benefit to patients in earlier treatment settings.”
OS data were immature at data cutoff; however, results showed a strong trend toward improved OS with trastuzumab deruxtecan.
The agent also exhibited a safety profile consistent with that observed in prior trials. Researchers observed no new safety concerns, and they reported no grade 4 or grade 5 treatment-related interstitial lung disease events.
Complete results of DESTINY-Breast03 will be submitted for presentation at a medical meeting.
“DESTINY-Breast03 is the first global phase 3 head-to-head trial of Enhertu against an active control and supports the potential of this medicine to become the new standard of care for patients with HER2-positive metastatic breast cancer following initial treatment with trastuzumab and a taxane,” Ken Takeshita, global head for research and development for Daiichi Sankyo, said in the release. “We believe this highly sophisticated and specifically engineered antibody-drug conjugate is fulfilling its promise to reshape the treatment of HER2-positive metastatic breast cancer, with the goal to move into earlier lines of treatment for HER2-positive breast cancer and many other HER2-expressing tumor types.”
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