Managing Hematologic Toxicities with ADCs: Neutropenia, Growth Factor Support, and Thrombocytopenia in Breast and Lung Cancer

Hope Rugo, MD; Aaron Lisberg, MD; and Liz Castronovo, NP, discuss hematologic toxicity management during antibody-drug conjugate (ADC) therapy across breast and lung cancer, with particular attention to neutropenia, febrile neutropenia, and growth factor strategies.

Dr. Lisberg describes a primarily reactive approach to granulocyte colony-stimulating factor (G-CSF) support, guided by NCCN guidelines, while becoming proactive in subsequent cycles for patients who demonstrate significant count depressions. He notes that datopotamab deruxtecan rarely requires growth factor support, whereas trastuzumab deruxtecan occasionally does. For febrile neutropenia, Dr. Lisberg stresses the importance of patient education from treatment initiation, instructing patients with fever to proceed directly to the emergency department without waiting for a callback—underscoring that sepsis protocols and broad-spectrum antibiotics should be initiated promptly given the life-threatening nature of this condition.

In breast cancer, sacituzumab govitecan presents a more significant neutropenia burden. Dr. Rugo describes a shift toward more liberal growth factor use, supported by label updates, and advocates for proactive G-CSF administration in patients with prior growth factor requirements or grade 2 neutropenia at day 8. Long-acting pegfilgrastim after day 8 can reduce clinic visits, although bone pain may require management with acetaminophen, nonsedating antihistamines such as loratadine, or occasionally low-dose dexamethasone. Castronovo emphasizes proactive support for heavily pretreated or frail patients, noting that patients with metastatic disease want to maximize quality time with family rather than managing preventable hospitalizations.

Throughout, the panel reinforces that early education about fever protocols, individualized growth factor strategies, and timely dose modifications are essential to preventing serious infections that could compromise both survival and treatment continuity.