Dr Chen on ADC-Related Toxicity Management Strategies in Breast Cancer

“In the future, what we will start to see is that oral SERDs are going to be paired with various different combination targeted therapies, and our ability to use these targeted therapies in the appropriate patients will define how these oral SERDs are used and who they should be for.”

Nan Chen, MD, an assistant professor of medicine at the University of Chicago Medicine, discussed considerations for managing antibody-drug conjugate (ADC)–associated toxicities in patients with breast cancer, as well as the evolving role of oral selective estrogen receptor degraders (SERDs) in ER-positive disease.

Chen began by emphasizing the management challenges inherent in using ADCs, detailing the adverse effect profiles of agents like sacituzumab govitecan-hziy (Trodelvy). She detailed the primary toxicities associated with this agent, identifying neutropenia and diarrhea as the most significant concerns. She highlighted that the implementation of prophylaxis for neutropenia has been effective in reducing the risks of high-grade and febrile neutropenia, either through the use of short-acting or long-acting granulocyte colony–stimulating factor. Regarding gastrointestinal issues, Chen noted that although various antidiarrheals are effective for management, the most important element for a smooth treatment course is robust patient counseling to ensure patients know what to expect.

Furthermore, Chen focused on the management of toxicities associated with fam-trastuzumab deruxtecan-nxki (Enhertu), specifically the unique risk of pneumonitis, which is observed in approximately 10% of patients treated with this agent. She stressed the importance of a vigilant monitoring workflow, which includes performing chest CT scans every 2 to 3 cycles and instructing patients to immediately report new respiratory symptoms.

Chen also addressed the role of oral SERDs, such as elacestrant (Orserdu) and imlunestrant (Inluriyo), for patients with ER-positive breast cancer harboring ESR1 mutations who have progressed on endocrine therapy with or without a CDK4/6 inhibitor. She cautioned that although this class of agents is generally well tolerated, the choice of a specific agent may be dictated by a patient’s individual tolerability profile, indicating that one oral SERD may be a suitable alternative if a patient cannot tolerate another.

Chen also noted the evolving landscape of combinations involving targeted therapies, where oral SERDs are expected to be paired with various other agents. She concluded that the ability to use these targeted therapies in the appropriate patient populations will define how they are used in the future.