Dose Modifications of Ribociclib and Endocrine Therapy for Treatment of ER+ HER2- metastatic Breast Cancer 

Abstract Purpose: Treatment for estrogen receptor positive (ER+), human epidermal receptor 2 negative (HER2-) metastatic breast cancer (MBC) has improved with the approval of CDK 4/6 inhibitors. Clinical trials with the CDK4/6 inhibitor ribociclib, suggest that between 35% to 57.5% of the patients experience a dose reduction during treatment. Information on the possible consequences of dose reduction concerning efficacy is needed. Methods: A retrospective cohort study on patients with ER+ HER2- MBC from three Danish oncology departments. Data on tolerability and progression-free survival were collected from electronic health records. Results: 128 patients with ER+ HER2- MBC who initiated ribociclib treatment between 1st January 2018 to 31st March 2020 were included in our analysis. Of these patients, 48.4% required one or more dose reductions. Overall median PFS was 19.2 months (CI-95%: 14.3-NR). Patients with one or more dose reductions did not have decreased median PFS (19.2 months, CI-95%: 14.3-NR compared to 12.2 months, CI-95%: 7.3-NR. p=0.078). Frequency of adverse events were as previously reported, with grade III and IV neutropenia occurring in 45.3% and 7% of patients, respectively. Patients treated with fulvestrant versus an aromatase inhibitor and patients with lymph node involvement at baseline had lower odds of requiring dose reduction (ORa = 0.30, CI-95%: 0.18-0.89 & ORa = 0.41, CI-95%: 0.12-0.73, respectively). Conclusion: Our results indicate that dose reduction of ribociclib is safe and do not compromise the efficacy of the treatment. Furthermore, the study supports translation of results from the MONALEESA trials to patients treated in real-world clinical settings.