Dr Tarantino on the Safety of T-DXd and T-DM1 in HER2+ Breast Cancer

Paolo Tarantino, MD, researcher, the European Institute of Oncology, clinical research fellow, Dana-Farber Cancer Institute, discusses the safety profiles of fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) and ado-trastuzumab emtansine (Kadcyla; T-DM1) when used in metastatic HER2-positive breast cancer, according to updated data from the phase 3 DESTINY-Breast03 trial (NCT03529110)

Both T-DM1 and T-DXd are generally well-tolerated agents in the treatment of patients with HER2-positive breast cancer, Tarantino begins, adding that most patients can receive these drugs without experiencing major adverse effects (AEs). Nausea and vomiting are common AEs associated with T-DXd, and necessitate proactive management. Adequate prophylaxis can significantly reduce the frequency and severity of these toxicities, making them more manageable for patients, he says. Additionally, both T-DM1 and T-DXd carry anti-HER2 antibodies, which can lead to cardiac toxicity in a small percentage of patients. This cardiac toxicity is usually low grade and reversible, but it underscores the importance of regular cardiac monitoring through baseline and periodic echocardiograms during treatment.

As these drugs carry chemotherapy agents, they can also cause cytopenias, which are generally manageable with appropriate medical intervention, Tarantino expands. T-DXd has been associated with high immunogenicity, necessitating careful management to prevent and address adverse immune responses. One of the most significant concerns with T-DXd is the risk of interstitial lung disease (ILD). Approximately 10% to 15% of patients may develop ILD with T-DXd, compared with less than 1% of patients treated with T-DM1, Tarantino explains. If ILD is suspected, the drug should be stopped immediately, and steroids should be administered. Reintroduction of T-DXd can be considered if ILD was asymptomatic and only noted on scans, but this is still under investigation. Current understanding suggests stopping the drug and administering steroids to avoid high-grade ILD, Tarantino emphasizes.

The DESTINY-Breast03 trial reinforced the importance of early detection and management of ILD, as no grade 5 ILD episodes were reported despite prolonged exposure to T-DXd, he reports. Overall, T-DM1 and T-DXd are effective and generally well-tolerated treatments for HER2-positive breast cancer, Tarantino says. Ensuring patient safety through proactive management of common AEs, such as nausea and vomiting, cardiac toxicity, cytopenias, and ILD, is essential, he concludes.