Palbociclib plus endocrine therapy in Premenopausal women in HR+/Her2- Breast Cancer with Visceral Metastases versus Combined Chemotherapy

Abstract

Background: Metastatic breast cancer HR+/Her2- type with visceral metastasis in premenopausal women is one of the most aggressive breast cancer types. The objective of this study was to evaluate the comparative efficacy of first-line Palbociclib in combination with endocrine therapy versus combination chemotherapy in premenopausal women with visceral metastases from hormone receptor-positive, HER2-negative metastatic breast cancer.

Methods: In this prospective, nonrandomized study, 105 patients were enrolled: Group1: 61 patients were treated with Palbociclib+ET, either with Fulvustrant/goserelin in 38 patients (62.3%) or with AI/goserelin in 23 patients (37.7%) Group2: 44 patients were treated with combined chemotherapy (Taxol/Carboplatin, Gemzar/Carboplatin, AC or Navelbine/Xeloda). The primary endpoint of the study was progression free survival (PFS) and secondary endpoints were overall survival (OS) and overall response rate (ORR).

Results: A total of 105 patients were identified; the median age was 44 years (range 34-55 years). The median follow up was 24 months. In the ET arm, 6 patients (9.8%) received ET as 1st line, 42 patients (68.9%) as 2nd line and 13 patients (11.3%) received more than 2 prior ET. The objective response rate was significantly higher in group 1 (34.4% vs.15.9%, p =0.018).

Similarly, mPFS was higher in group 1 9.93 months compared to 6.03 months in group 2 (HR=0.64, 95% CI: 0.50–0.82, p=0.001), mOS was not reached in both groups, however 1 year OS rates were 81.82% in chemotherapy arm vs 88% in endocrine arm (HR=0.65, 95% CI: 0.48–0.88, p=0.005). Among the patients receiving palbociclib and endocrine therapy, mPFS was higher in the endocrine group regarding <40 years (17.33 vs 4.67 months P value 0.026), non-obese women (9.93 vs 6.13 months P value 0.046), PR positive tumor and multiple metastatic sites (6.7 vs 4.97 months P 0.015)

 Safety: 90.16% in ET arm developed at least 1 AE vs 88.57% in chemotherapy arm, most common was neutropenia in 86.89% with ET, while in chemotherapy arm, GIT symptoms were found in 52.27% and neutropenia in 45.45%. GIII-IV toxicities were in 18.03% vs 18.18 in ET and chemotherapy respectively.

Conclusion: This is a real-world study to assess the effectiveness of Palbociclib plus endocrine therapy vs combined chemotherapy in premenopausal women with HR+/Her2- breast cancer who have visceral metastases. Palbociclib+ET was superior to combined chemotherapy in the objective response rate, median progression free survival.