FDA expands Enhertu approval for breast cancer
Key takeaways:
- The FDA approved trastuzumab deruxtecan for a new breast cancer indication.
- The approval applies to patients with HER2-low or HER2-ultraow metastatic disease that progressed after endocrine therapy.
The FDA expanded the approval of trastuzumab deruxtecan for treatment of breast cancer.
The new indication applies to use of the agent by patients with HER2-low or HER2-utralow metastatic breast cancer whose disease progressed after at least one endocrine therapy.
Trastuzumab deruxtecan (Enhertu; AstraZeneca, Daiichi Sankyo) is a HER2-directed antibody-drug conjugate.
The agent is approved in the United States for several indications, including treatment of adults with unresectable or metastatic HER2-positive breast cancer who received two or more prior anti-HER2-based regimens; adults with HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma who received a prior trastuzumab (Herceptin, Genentech)-based regimen; and adults with unresectable or metastatic HER2-positive solid tumors who received previous systemic therapy and lack additional treatment options.
The FDA based the new indication on results of the randomized phase 3 DESTINY-Breast06 trial, which included 866 patients with hormone receptor-positive metastatic breast cancer.
All trial participants had received prior endocrine-based therapy and the majority (90.4%) had received targeted therapy with a cyclin dependent kinase 4/6 inhibitor. None had received chemotherapy for metastatic breast cancer.
The majority (82.3%; n = 713) had HER2-low disease, whereas 17.6% (n = 153) had HER2-ultralow disease.
Researchers randomly assigned 436 participants to 5.4 mg/kg trastuzumab deruxtecan every 3 weeks. The other 430 received physician’s choice of chemotherapy (capecitabine, 59.8%; nab-paclitaxel, 24.4%; or paclitaxel, 15.8%).
PFS in the HER2-low population served as the primary endpoint. PFS in the intent-to-treat population (HER2-low and HER2-ultralow), OS, objective response rate and safety served as secondary endpoints.
Results showed longer median PFS with trastuzumab deruxtecan in the overall study population (13.2 months vs. 8.1 months; HR = 0.64; 95% CI, 0.54-0.76). ORR analyses favored trastuzumab deruxtecan (62.6% vs. 34.4%).
The benefit appeared consistent between the HER2-low and HER2-ultralow cohorts.
“Endocrine therapy is typically used in the initial treatment of hormone receptor-positive metastatic breast cancer and, following progression, subsequent chemotherapy is associated with poor outcomes,” Aditya Bardia, MD, MPH, a DESTINY-Breast06 investigator and program director of breast oncology at UCLA Health Jonsson Comprehensive Cancer Center, said in a press release. “With a median progression-free survival exceeding 1 year and a response rate of more than 60%, trastuzumab deruxtecan offers a potential new standard of care for patients with hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer following endocrine therapy.”
Read more about