Dr Cairo on the Safety Profiles of T-DM1 vs T-DXd in HER2+ Metastatic Breast Cancer

Michelina Cairo, MD, Sarah Cannon Research Institute, Texas Oncology, The US Oncology Network, discusses the adverse effect (AE) profiles of ado-trastuzumab emtansine (Kadcyla) and fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with HER2-positive metastatic breast cancer.

Although trastuzumab emtansine was a standard second-line therapy for patients with HER2-positive metastatic breast cancer, findings from the phase 3 DESTINY-Breast03 trial (NCT03529110) showed improved efficacy with trastuzumab deruxtecan vs trastuzumab emtansine in this population. Despite these efficacy benefits with trastuzumab deruxtecan, it is important to consider the safety profiles of both agents when determining which will be most tolerable for individual patients and provide them with the greatest quality of life (QOL), Cairo says.

In DESTINY-Breast03, gastrointestinal AEs, including nausea, were common, with any-grade nausea occurring in 77% of patients in the trastuzumab deruxtecan arm vs 30% of those in the trastuzumab emtansine arm. However, when using trastuzumab deruxtecan in clinical practice, nausea can be well managed, and the incidence of vomiting with this agent is often reduced from the incidence seen in DESTINY-Breast03, Cairo explains.

Another AE to be aware of when considering patient QOL is alopecia, Cairo emphasizes. In DESTINY-Breast03, the trastuzumab deruxtecan arm had a 40% any-grade alopecia incidence vs a 3% incidence in the trastuzumab emtansine arm. It is important to counsel patients about the likelihood of grade 1 or 2 alopecia, especially patients who did not previously experience hair loss when they received trastuzumab (Herceptin) plus pertuzumab (Perjeta), Cairo notes.

The rate of any-grade neutropenia was higher with trastuzumab deruxtecan, at 31% vs 11% with trastuzumab emtansine. The rate of grade 3 or higher neutropenia was 16% with trastuzumab deruxtecan vs 3% with trastuzumab emtansine. Additionally, patients who received trastuzumab emtansine in this trial were more likely to experience increased liver function test abnormalities than those who received trastuzumab deruxtecan.

Across all trials with trastuzumab deruxtecan in breast cancer, interstitial lung disease (ILD) has an approximately 12% incidence vs an approximately 1.9% incidence across all trials with trastuzumab emtansine, according to Cairo. It is important to be aware of and knowledgeable about ILD in all treatment lines, Cairo says. However, since the incidence of ILD has increased in patients receiving trastuzumab deruxtecan, everolimus (Afinitor), taxanes, and CDK4/6 inhibitors, physicians now have a greater ability to recognize it on scans and initiate treatments early, Cairo concludes.