Time to next treatment to evaluate the therapeutic sequence after first- or second-line CDK4/6 inhibitors of hormone receptor-positive, HER2-negative advanced breast cancer in Italy: a retrospective/prospective observational trial GOIRC-04-2019

Background: Palbociclib, ribociclib, and abemaciclib are approved for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (aBC), in combination with aromatase inhibitors or fulvestrant. However, there is no standard care following progression on cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). Materials and methods: This study aimed to evaluate treatment patterns and effectiveness following the failure of CDK4/ 6i therapy. The analysis included 407 patients who received CDK4/6i in first- or second-line treatment across three cancer centers. Primary endpoints included time to next treatment (TTNT) and real-world progression-free survival. Results: The results demonstrated a median TTNT (mTTNT) of 26 months [95% confidence interval (CI) 21-31 months] for patients receiving CDK4/6i as first-line treatment. Subsequent therapies, including chemotherapy (CT), endocrine therapy (ET) with or without everolimus, and CDK4/6i-based regimens, were evaluated. The mTTNT for second-line treatments was 13 months (95% CI 9-16 months), with CT showing the longest duration [24 months (95% CI 17-30 months) versus 15 months (95% CI 11-18 months)] for CDK4/6-based regimens versus 9.6 months for everolimus with or without ET (95% CI 6-11 months). Multivariate analysis identified the number of disease sites as a significant predictor of longer TTNT in the first-line setting. Safety data revealed that CDK4/6i dose reductions due to toxicity occurred in 47% of patients, with neutropenia being the most common adverse event. Conclusions: These findings emphasize the variability in treatment efficacy following CDK4/6i therapy and underscore the importance of personalized treatment strategies. Further research is needed to optimize therapeutic sequences and improve patient outcomes in this setting.