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Standard of Care Regimens for Second-Line Treatment of HER2+ Metastatic Breast Cancer

Laura Spring, MD, and Manali Bhave, MD, discuss findings from the DESTINY-Breast03 trial and how these results have led them to adopt T-DM1 as the new standard of care over lapatinib/capecitabine for second-line treatment of HER2-positive metastatic breast cancer after progression on first-line trastuzumab and a taxane.

The discussion moves to second-line treatment for this patient who progressed after around 18 months on first-line taxane, trastuzumab and pertuzumab.

Spring states that based on the groundbreaking DESTINY-Breast03 trial, trastuzumab deruxtecan (T-DXd) is now the standard second-line treatment over T-DM1. She highlights the impressive median treatment duration of 18.2 months for T-DXd versus 6.9 months for T-DM1, and the 36% reduced risk of death with T-DXd.

However, Spring notes there may be scenarios where T-DM1 is preferred, such as a patient with prior pneumonitis who may be higher risk for the interstitial lung disease seen with T-DXd. Patient preference can also play a role if they are more concerned about the side effect profile of T-DXd like alopecia compared to T-DM1. Factors like pace of disease, sites of metastases, and duration of first-line response help guide the decision.

Bhave agrees T-DXd is their standard second-line choice but emphasizes the need to be upfront with patients about potential toxicities like fatigue, nausea requiring dose modifications, and recommends aggressive anti-nausea prophylaxis. Both agree following the dose modification guidelines for T-DXd is important for tolerability, as the fatigue can be significant with longer use.

In summary, while T-DXd has become the preferred second-line option, there is still a role for T-DM1 in certain clinical scenarios or based on patient preference and anticipating side effect management.

This summary was AI-generated and edited for clarity.

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Albert Grinshpun, MD, MSc, head, Breast Oncology Service, Shaare Zedek Medical Center
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