Safety Management: Managing Treatment-Related Toxicities

When incorporating ADCs into treatment for mTNBC, it is crucial to consider their adverse effect profiles, despite their targeted nature. One notable adverse event associated with sacituzumab govitecan is neutropenia, which can lead to serious complications such as febrile neutropenia. To mitigate this, clinicians increasingly use prophylactic growth factor support. A common approach involves administering long-acting growth factors after day 8 of the treatment cycle and short-acting factors for several days after day 1. In some cases, particularly with frail or heavily pretreated patients, prophylactic support is initiated from the start of treatment to prevent neutropenia altogether.

Identifying patients at higher risk for adverse effects is essential for personalized care. Factors such as advanced age, prior chemotherapy exposure, and early signs of myelosuppression help inform decisions around supportive therapies. In addition to clinical risk factors, genetic factors are also gaining attention. Specifically, polymorphisms in the UGT1A1 gene have been associated with a greater risk of neutropenia and diarrhea in patients receiving sacituzumab govitecan. While testing for these polymorphisms is not currently standard practice, it is becoming more feasible due to advancements in circulating tumor DNA testing, which can now include genotyping for variants such as UGT1A1.

Given these developments, there is growing support for incorporating genetic screening into routine care, particularly for patients considered at higher risk for toxicity. For individuals identified with a detrimental UGT1A1 polymorphism, a dose reduction of sacituzumab govitecan at initiation may be advisable to reduce the likelihood of severe adverse effects. This proactive approach, combining clinical assessment with genomic insights, allows for more tailored and safer use of ADCs in the evolving treatment landscape of mTNBC.