Enhertu receives breakthrough therapy designation for second-line breast cancer treatment
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The FDA granted breakthrough therapy designation to trastuzumab deruxtecan for second-line treatment of patients with metastatic HER2-positive breast cancer.
The designation applies to use of the agent by patients who received at lease one prior anti-HER2-based regimen.
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 FDA based the breakthrough therapy designation on results of the randomized phase 3 DESTINY-Breast03 trial.
The open-label 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 (Herceptin, Genentech) 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.
Results presented at this year’s virtual ESMO Congress showed trastuzumab deruxtecan reduced risk for progression or death by 72% (HR = 0.28; 95% CI, 0.22-0.37). A higher percentage of patients assigned trastuzumab deruxtecan than ado-trastuzumab emtansine achieved confirmed objective response (79.7% vs. 34.2%) and remained alive at 1 year (94.1% vs. 85.9%).
The safety profile of trastuzumab deruxtecan appeared consistent with that observed in prior clinical trials. No grade 4 or grade 5 treatment-related interstitial lung disease events occurred.
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