Combination therapy with trastuzumab and deruxtecan yields lower risk of disease progression or death than trastuzumab plus emtansine in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer previously treated with trastuzumab and a taxane, according to new study results.  

On the other hand, the investigation also found that treatment with trastuzumab-deruxtecan was associated with greater risk of interstitial lung disease and pneumonitis.  

According to principal investigator Javier Cortés, MD, PhD, of the European University of Madrid, a total of 524 patients were randomized, representing 169 centers in 15 countries. Of these, 75.8% of the 261 who received trastuzumab-deruxtecan were alive without disease progression at 12 months, compared with 34.1% of their 263 counterparts who received trastuzumab plus emtansine—yielding a hazard ratio for disease progression or death from any cause of 0.28 (95% CI 0.22-0.37; P<0.001).  

Of patients treated with trastuzumab-deruxtecan combination therapy, 94.1% were alive at 12 months, compared with 85.9% of those treated with trastuzumab-emtansine therapy (HR for death: 0.55; 95% CI 0.36-0.86). Yet despite this difference, the researchers noted that the prespecified significance boundary was not reached.  

Overall response—which was defined as either complete or partial response—was observed in 79.7% of study participants treated with trastuzumab-deruxtecan and 34.2% of those who received trastuzumab-emtansine.  

Interestingly, researchers found that adjudicated drug-related interstitial lung disease or pneumonitis occurred in 10.5% of individuals who underwent treatment with trastuzumab and deruxtecan, compared with 1.9% of those in the trastuzumab-emtansine group.  

None of these events, however, were grade 4 or grade 5. The researchers said the incidence of these events was numerically lower than what has been found in previous research. 

The findings demonstrate the “superiority” of trastuzumab-deruxtecan over trastuzumab-emtansine with respect to reducing the risk of progression or death in patients with HER2-positive metastatic breast cancer who had been previously treated with trastuzumab and a taxane. 
 

Disclosure: Some authors declared financial ties to drugmakers. See full study for details. The study was funded by Daiichi Sankyo and AstraZeneca. 

Reference: 
https://www.nejm.org/doi/full/10.1056/NEJMoa2115022?query=featured_hematology-oncology 

Images: Getty Images, Pixabay 

By Michael Vlessides, MD /alert Contributor