Clinical benefits with trastuzumab deruxtecan in HER2+ metastatic breast cancer

April 2022 Cancer trials Nalinee Pandey

A recent study published in the March issue of the New England Journal of Medicine reports that the risk of progression or death from any cause is lower with trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who were previously treated with trastuzumab and a taxane.

Trastuzumab emtansine is the current standard of care for HER2+ breast cancer patients whose disease progresses after trastuzumab + taxane therapy. Researchers from the International Breast cancer centre in Barcelona, Spain, have evaluated the efficacy and safety of an antibody-drug conjugate, trastuzumab deruxtecan.

Study design

The phase-3, open-label, multicenter study enrolled 524 HER2+ breast cancer patients who had received treatment with trastuzumab + taxane and compared the efficacy and safety of trastuzumab deruxtecan versus trastuzumab emtansine. The study’s primary endpoint was progression-free survival (PFS), and the secondary endpoint’s included overall survival (OS), objective response, and safety.

Main findings

Researchers found that a higher percentage of patients (75.8%) were alive without disease progression at 12 months with trastuzumab deruxtecan when compared to those treated with trastuzumab emtansine (34.1%, hazard ratio for progression or death from any cause, 0.28; 95% CI, 0.22 to 0.37; P<0.001). The corresponding percentage of patients alive at 12 months was 94.1 % (trastuzumab deruxtecan) and 85.9% (trastuzumab emtansine). The overall response was observed in 79.7 and 34.2 per cent of the patients, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 98.1% with trastuzumab deruxtecan and 86.6% with trastuzumab emtansine. Further, TRAEs of grades 3 or 4 were 45.1 and 39.8%, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis was seen in trastuzumab deruxtecan (10.5%) and trastuzumab emtansine (1.9%) groups.

Conclusion

The clinical study demonstrates that trastuzumab deruxtecan is an effective new treatment option for HER2+ breast cancer patients previously treated with trastuzumab and a taxane.

Reference

Cortés J, Kim SB, Chung WP, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022 Mar 24;386(12):1143-1154. doi: 10.1056/NEJMoa2115022. PMID: 35320644.

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