Retrospective evaluation of the efficacy of CDK4/6 inhibitors compared to ER and PR levels in hormone receptor positive HER2 negative metastatic breast cancer patient

CDK4/6 inhibitors with aromatase inhibitors as the first-line standard-of-care in hormone receptor (HR) positive, human epidermal growth factor receptor-2 (HER2)- negative advanced breast cancer. Phase III studies examining CDK4/6 inhibitors have not identified significant predictive or prognostic markers.In this study, we aimed to restrospectively evaluate the efficacy of CDK4/6 inhibitors according to ER and PR levels in HR+, HER2 (-) metastatic breast cancer. Methods 171 patients were evaluated retrospectively. Patients were divided into 2 groups as ER level ≥90 (n=119) and <90 (n=52). Demographic characteristics, histopathologic findings, menopausal status, presence of visceral metastases, treatment response and side effects were evaluated in both groups. Results The mean age was 55 years, 75% of the patients were postmenopausal and 67% were denova metastatic. Visceral metastases were present in 73% of the patients, 53% of the patients had received this treatment second line and beyond. 87% of the patients had clinical benefit, 12% were primary non-responders. Patients with ER<90 were younger, higher grade (p=0.018), had more liver metastases (p=0.009),reached CDK4/6 therapy later, and had shorter follow-up. Duration of response(DOR ) was statistically longer in those who received first-line treatment (21.3 months vs. 11 months, p=0.034). In the ER≥90 group, OS was not reached independently of the treatment line, while in the <90 group, OS was not reached in the first-line group and 30 months in the second-line group. The longer time until CDK4/6 inhibitor therapy was associated with statistically significant shorter OS (NR-33.9 months p=0.019) and no significant impact of PR level or HER2 status on overall survival. Median PFS was 50 months, with no statistical differences based on ER and PR levels. Receiving second or later line therapy significantly shortened PFS. Conclusions In this study, it was observed that the levels of ER and PR were not predictive or prognostic in patients receiving CDK4/6 inhibitor. However, the time until the initiation of treatment impacted OS and PFS, with PR levels being associated with more aggressive disease.