Abstract PO4-04-13: Impact of dose reduction of CDK4/6 inhibitors on progression-free survival in Mexican patients with hormone receptor-positive, HER2-negative metastatic breast cancer: a retrospective single-center study
Authors: Meraz-Brenez Andres , Aranda-Gutierrez Alejandro , Gonzalez-Sanchez Hector Raul , Martinez-Cannon Bertha Alejandra , Verduzco-Rodriguez Leonardo , Verduzco-Aguirre Haydee Cristina 
Published: May 2024

Background

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have been demonstrated to prolong survival in women with hormone receptor-positive, HER-2 negative, metastatic breast cancer. However, these treatments often require dose adjustments due to adverse effects, resulting in a reduction in 30-50% of cases. There is evidence suggesting a relationship between dose intensity and progression-free survival (PFS), but data in the Hispanic population are limited. Therefore, the objective of the study was to explore the association between dose reduction of CDK4/6/i inhibitors and PFS in patients with metastatic breast cancer.

Methods

We conducted a retrospective single-center study involving patients diagnosed with hormone receptor-positive, HER-2 negative metastatic breast cancer (MBC) between 2020 and 2023. Eligible patients were those who received at least one cycle of palbociclib, abemaciclib, or ribociclib and had a follow-up period of more than three months since the initiation of CDK4/6 inhibitor (CDK4/6i) treatment. Patient data were collected from electronic medical records. We analyzed demographic and clinicopathological characteristics and estimated the PFS in patients who had any dose reduction within the first 12 weeks compared to those who did not, using Kaplan-Meier plots and compared the differences in survival using the log-rank test. A Cox regression analysis was performed to estimate survival hazard ratios (HR).

Results

Among 41 patients, the mean age at CDK4/6i initiation was 61.0 years (SD 12.9), 22 (53.7%) were postmenopausal at diagnosis, 25 (61%) had recurrent disease, and 22 (53.7%) were receiving CDK4/6i in the first-line setting. Bone metastases were present in 30 (73.2%), and visceral metastases in 22 (53.7%). Regarding type of CDK4/6i, 33 (80.5%) received palbociclib, 7 (17.1%) ribociclib, and 1 (2.4%) abemaciclib. At 12 weeks, 12 patients (29.3%) had a dose reduction (Table 1).

With a median follow-up since CDK4/6i initiation of 407 days (95% confidence interval (CI) 272-542), 19 events were recorded, with a median PFS of 12.6 months (95% CI 8.0-17.3) for the overall population. Median PFS was 9.7 months (95% CI 0.6-18.8) in patients who had a dose reduction at 12 weeks and 35.2 months (95% CI 0-72.2) in those who did not (p=0.014). The univariate Cox proportional hazard model showed that dose reduction was associated with a worse PFS (hazard ratio 3.1; 95% CI: 1.20–7.80, p = 0.0019)

Conclusion

In this cohort of Mexican patients with hormone receptor-positive, HER2-negative metastatic breast cancer we found that dose reduction of CDK4/6 inhibitors within the first 12 weeks of treatment was associated with worse PFS. Given the retrospective nature of this analysis, we believe that these findings should be replicated in prospective studies.

Table. Patient characteristics

Citation Format: Andres Meraz-Brenez, Alejandro Aranda-Gutierrez, Hector Raul Gonzalez-Sanchez, Bertha Alejandra Martinez-Cannon, Leonardo Verduzco-Rodriguez, Haydee Cristina Verduzco-Aguirre. Impact of dose reduction of CDK4/6 inhibitors on progression-free survival in Mexican patients with hormone receptor-positive, HER2-negative metastatic breast cancer: a retrospective single-center study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-13.