Dr Lang on Real-World Safety Data for Perioperative Pembrolizumab in Early TNBC

"[Approximately] 40% of patients had immune-related adverse [effects] that were noteworthy, and surgeons should be aware of these."

Julie Lang, MD, chief of Breast Surgery at the Lerner Research Institute and co-leader of the Breast Cancer Program at Cleveland Clinic, discusses findings from a real-world, retrospective study evaluating the safety of the perioperative treatment regimen from the phase 3 KEYNOTE-522 trial (NCT03036488)—neoadjuvant pembrolizumab (Keytruda) in combination with chemotherapy, followed by adjuvant pembrolizumab—and the implications of these findings for surgical planning in patients with early-stage triple-negative breast cancer (TNBC).

The analysis focused on immune-related adverse effects (irAEs) associated with the regimen, particularly endocrinopathies, which were observed in approximately 40% of patients. These included thyroid dysfunction, adrenal insufficiency such as Addison’s disease, and abnormalities in glucose regulation. Lang emphasizes that such toxicities are clinically significant and may require modifications to perioperative management. The findings underscore the importance of multidisciplinary coordination, particularly with endocrinology, for appropriate preoperative risk assessment.

Early in the adoption of the KEYNOTE-522 regimen, standardized protocols for monitoring thyroid function, cortisol, and glucose were not uniformly implemented. This led to missed or delayed recognition of irAEs, prompting changes in institutional practices. Lang notes that routine endocrine evaluation—including testing of thyroid-stimulating hormone and cortisol—is now advised for all patients receiving pembrolizumab-based neoadjuvant therapy.

Importantly, some endocrinopathies appear to persist beyond the treatment period, raising concerns about the long-term implications for patient health and survivorship. Lang highlights the need for ongoing collaboration with endocrinology colleagues to determine the chronicity of these toxicities and whether they represent permanent sequela of immune checkpoint inhibition.

Overall, Lang concludes that although the KEYNOTE-522 regimen improves pathologic complete response rates in early-stage TNBC, it also introduces a spectrum of irAEs that may influence surgical planning and long-term management.