362P - Dose reductions due to treatment-related side effects and survival outcomes in breast cancer patients treated with CDK4/6 Inhibitors

Background

CDK4/6 inhibitors play a crucial role in managing hormone receptor-positive, HER2-negative advanced breast cancer, though they often necessitate dose reductions or temporary stops due to side effects. This study aimed to investigate the effects of dose reductions due to treatment-related side effects on long-term survival in patients treated with CDK4/6i for breast cancer.

Methods

This retrospective, observational cohort study includes HR+ HER2- MBC patients treated with CDK4/6 inhibitors at a single center in Türkiye between 2018 and 2023.

Results

428 patients data analysed. The mean age of the cohort was 57.4 (± 12.4) years, and the median follow-up duration was 29.2 months (95% CI: 26.8-31.6). Dose modifications due to treatment-related toxicities were necessitated in 147 patients (34.3%). Hematologic toxicity was the predominant cause for dose reduction (26.2%), followed by cardiac toxicity (2.6%), hepatotoxicity (1.6%), and fatigue (1.4%). Among individuals undergoing dose reduction, a subset of 37 patients (25%) required subsequent dose reduction, primarily attributed to hematologic toxicity (7.5%). mPFS was determined to be 19.3 months (95% CI: 14.9-23.7) in the group of patients who did not undergo dose reduction. In patients who underwent one dose reduction and two dose reductions, mPFS was determined to be 23.5 (95% CI: 16.1-30.9) and 23.4 months (95% CI: 12.4-34.4). mOS of patients who did not undergo dose reduction was 57.75 months (95% CI: 27.8-87.7), while the mOS could not be reached in the group of patients who underwent dose reduction (p=0.065).

Conclusions

Although nearly one-third of patients required dose reductions, these adjustments did not compromise PFS, as evidenced by the comparable or slightly better mPFS in patients who underwent dose reductions. However the long-term impact on overall survival remains inconclusive, as the mOS was not reached in the dose-reduction group, and statistical significance was not achieved. These results underline the necessity of personalized dosing strategies to optimize treatment efficacy while minimizing adverse effects, warranting further investigation into the long-term outcomes of dose adjustments in this patient population.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.