Second-line treatment with trastuzumab deruxtecan resulted in superior overall survival outcomes when compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer, according to updated DESTINY-Breast03 trial results presented at SABCS 2022. 

The study comprised 524 patients treated with trastuzumab and a taxane in the metastatic setting, as well as those who experienced progression within 6 months in the neoadjuvant setting.  
 
Researchers randomly assigned patients to trastuzumab deruxtecan (5.4 mg/kg every 3 weeks; n = 261) or trastuzumab emtansine (3.6 mg/kg every 3 weeks; n = 263) until confirmed disease progression. 

At time of reporting, the median follow-up was 28.4 months (range, 0-46.9) for patients assigned trastuzumab deruxtecan and 26.5 months (range, 0-45) for patients assigned trastuzumab emtansine.  

Treatment with trastuzumab deruxtecan was associated with a 36% reduction in the risk of death (HR = 0.64; 95% CI, 0.47-0.87; P = .0037).  
 
Median OS was not reached in either arm, with 72 OS events observed in those assigned trastuzumab deruxtecan and 97 OS events observed among patients on trastuzumab emtansine. 

Median OS favored trastuzumab deruxtecan at 12 months (94.1% vs 86%), 24 months (77.4% vs 69.9%), and 36 months (69.3% vs 55.4%).  
 
The P value for OS crossed the .013 boundary and was considered statistically significant. 

Updated PFS data affirmed the previously reported superiority of trastuzumab deruxtecan, according to the researchers. 

The confirmed objective response rate significantly favored trastuzumab deruxtecan (78.5% vs 35%; P < .0001).  
 
In total, 21.1% of patients assigned trastuzumab deruxtecan achieved a complete response compared to 9.5% with trastuzumab emtansine. 

Researchers reported similar rates of treatment-emergent adverse events and serious adverse events. A greater proportion of patients assigned trastuzumab deruxtecan required drug interruptions and discontinuations. 

“With this OS analysis, we can confirm that the previously demonstrated benefit from trastuzumab deruxtecan in PFS improvement transforms into a statistically significant improvement in overall survival, a substantial advantage for our patients,” Sara A. Hurvitz, MD, professor of medicine at UCLA’s David Geffen School of Medicine in the press release. 

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Reference: 

Hurvitz S. T-DXd yields longer overall survival than T-DM1 in patients with HER2-positive metastatic breast cancer. SABCS 2022 (San Antonio Breast Cancer Symposium). 

Disclosures: Hurvitz declared financial ties to drugmakers. DESTINY-Breast03 is being supported by Daiichi Sankyo and AstraZeneca. 

Photo Credit: Getty Images.  

By Cameron Kelsall, MD /alert Contributor