Treatment with trastuzumab deruxtecan led to significant improvements in progression-free survival and overall survival in patients with HER2-low unresectable or metastatic breast cancer, according to phase 3 study results presented at the ASCO 2022 Annual Meeting. 

The researchers previously observed the efficacy of trastuzumab deruxtecan in HER2-low patients in a phase 1 study. They sought to determine its safety and efficacy as a treatment in a metastatic setting for patients with prior exposure to chemotherapy. 

In the DENSITY-Breast04 study, study authors enrolled 557 patients with confirmed HER2–low metastatic breast cancer, whom they randomly assigned to trastuzumab deruxtecan (5.4 mg/kg; n = 373) or physician’s choice of therapy (n = 184). Options in the latter category included capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel. 

In total, 88.7% of patients assigned to trastuzumab deruxtecan and 88.6% assigned to physician’s choice therapy had HR-positive disease.  

Median follow-up was 18.4 months (95% CI, 17.9-19.1). By treatment arm, median duration of treatment was 8.2 months for patients assigned trastuzumab deruxtecan (range, 0.2-33.3) and 3.5 months for patients assigned physician’s choice of therapy (range, 0.3-17.6). 

The study met its primary efficacy endpoint by demonstrating a significant PFS improvement in patients with HR-positive disease (median, 10.1 months vs 5.4 months; HR = 0.51; 95% CI, 0.4-0.64; P < .0001). The PFS benefit of trastuzumab deruxtecan extended to the full analysis set (9.9 months vs 5.1 months; HR = 0.5; 95% CI, 0.4-0.63; P < .0001). 

The median OS was significantly improved in the trastuzumab deruxtecan arm in patients with HR-positive disease (23.9 months vs 17.5 months; P = .0028) and in the full analysis set (23.4 months vs 16.8 months; P = .0010). 

Grade 3 or higher treatment-emergent adverse events occurred in 52.6% of the trastuzumab deruxtecan arm and 67.4% of the physician’s choice arm. Drug-related interstitial lung disease/pneumonitis affected 45 patients in the trastuzumab deruxtecan arm compared with 1 patient in the physician’s choice arm. 

“DESTINY-Breast04 is the first phase 3 trial of a HER2-directed therapy in patients with HER2-low metastatic breast cancer to show a statistically significant and clinically meaningful benefit in PFS and OS compared to standard-of-care treatment, regardless of HR status,” David A. Cameron, MD , professor of medical oncology at the University of Edinburgh Cancer Centre in Scotland, and colleagues concluded. 

Reference: 
https://meetinglibrary.asco.org/user/login?destination=%2Fembargo%2Frecord%2F209021%2Fabstract 

Disclosures: Cameron declared financial ties to drugmakers. See full abstract for details. Daiichi Sankyo and AstraZeneca provided funding for the study. 

Photo Credit: Getty Images.  

By Cameron Kelsall, MD /alert Contributor