Welcome back to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we’ll provide another quick update on a recent FDA cancer drug approval.
On May 4, 2022, the FDA approved fam-trastuzumab deruxtecan-nxki (brand name Enhertu) for adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within 6 months of completing therapy.
In December 2019, fam-trastuzumab deruxtecan-nxki received accelerated approval for adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. The following trial was the confirmatory trial for the accelerated approval.
Efficacy was based on DESTINY-Breast03, a multicenter, open-label, randomized trial that enrolled 524 patients with HER2-positive, unresectable, and/or metastatic breast cancer who received prior trastuzumab and taxane therapy for metastatic disease or developed disease recurrence during or within 6 months of completing neoadjuvant or adjuvant therapy. Patients were randomized 1:1 to receive either Enhertu or ado-trastuzumab emtansine by intravenous infusion every 3 weeks until unacceptable toxicity or disease progression. Randomization was stratified by hormone receptor status, prior treatment with pertuzumab, and history of visceral disease.
The main efficacy outcome measure was progression-free survival as assessed by blinded independent central review based on RECIST v.1.1. Overall survival and confirmed objective response rate were the key secondary outcome measures. Median progression-free survival was not reached in the Enhertu arm and 6.8 months in the ado-trastuzumab emtansine arm. The hazard ratio was 0.28 . At the time of the progression-free survival analysis, 16% of patients had died and overall survival was immature. The objective response rate based on the patients with measurable disease assessed by blinded independent central review at baseline was 82.7% in the Enhertu arm and 36.1% for those receiving ado-trastuzumab emtansine.
The prescribing information includes a Boxed Warning to advise health professionals of the risk of interstitial lung disease and embryo-fetal toxicity.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. The application reviews may be ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Full prescribing information for these approvals can be found on the web at www.fda.gov/drugsatFDA.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting Program at www.fda.gov/medwatch.
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