105P CDK4/6 inhibitors in hormone receptor-positive, HER2-negative, locally advanced breast cancer (LABC): Biological and clinical activity, and post-surgical approaches

Abstract

Endocrine therapy (ET) combined with cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) represents an alternative to chemotherapy (CT) in patients (pts) with hormone receptor-positive, HER2-negative (HR+/HER2-) LABC. Limited data exist on the real world and effectiveness of CDK4/6i and the post-surgical treatment patterns in this setting. Clinical and pathological data of consecutive pts with HR+/HER2- LABC treated with CDK4/6i + letrozole (+ ovarian suppression, if premenopausal) at the University “Federico II” and the National Cancer Institute “G. Pascale” (Naples, Italy) between July 2018 and July 2021 were collected. Study objectives included evaluation of clinical and pathologic responses, HR, HER2 and Ki67 expression in pre- and post-treatment tumor samples, post-surgical loco regional and systemic treatments. Fifty-nine pts (56% postmenopausal) were included in this study. Among these, 25 (42%), 29 (49%), and 5 (9%) pts received palbociclib, ribociclib, and abemaciclib, respectively. After a median duration of 7.5 months (range 1-16), 48 (81%) pts achieved an objective response and underwent surgery, however, no pathological complete response was detected. Three pts experienced disease progression during the treatment, while 8 pts were still under therapy at the time of this analysis. The mean expression of progesterone receptor and Ki67 significantly decreased in residual tumors compared to baseline (paired t-test P <0.001). After surgery, 24% of pts continued ET + CDK4/6i, 48% received anthracycline and/or taxane-based CT followed by ET, and 29% were treated with ET alone. Age <65 years, presence of residual disease >2 cm in breast and/or lymph node metastases after CDK4/6i were associated with CT use (chi-square t-test <0.05). CDK4/6i + ET showed biological and clinical activity in HR+/HER2- LABC. Treatment of physician's choice in pts who achieved tumor down staging and conversion to surgery was not uniform, probably due to the lack of evidence-based recommendations. Further clinical investigations are needed to define the optimal treatment approach for HR+/HER2- LABC.