Reflections on adjuvant pembrolizumab for triple-negative breast cancer treated with the KEYNOTE-522 regimen: Is it really necessary?

Gains in event-free and overall survival from the KEYNOTE-522 trial have incorporated pembrolizumab into the neoadjuvant and adjuvant armamentarium for stage II-III triple-negative breast cancer (TNBC). However, the lack of a second randomization to pembrolizumab after surgery raises the question of whether the adjuvant phase of this immunotherapeutic agent is necessary, both in patients who achieve a pathological complete response (pCR) and in those with residual disease. Thus, the KEYNOTE-522 design established the use of adjuvant pembrolizumab as current standard of care without demonstrated benefit of the adjuvant part. Some studies in patients with specific types of cancer, including TNBC, suggest that adjuvant immunotherapy may not provide a benefit. Furthermore, no study has evaluated the role of adjuvant immunotherapy specifically following neoadjuvant chemoimmunotherapy. Additionally, concerns regarding chronic toxicities and the use of health care resources including costs of the adjuvant treatment have raised concerns in the oncologic community. Baseline presence of tumor-infiltrating lymphocytes and absence of circulating tumor DNA or specific molecular subtypes are associated with pCR and have been proposed as biomarkers predicting outcomes in trials of immunotherapy in localized TNBC, but no data on these biomarkers from the KEYNOTE-522 trial have been published to clarify the benefit of adjuvant pembrolizumab. This commentary discusses the available evidence, ongoing controversies, knowledge gaps and future perspectives regarding adjuvant immunotherapy in early TNBC.