Outcome of Everolimus-Based Therapy in Hormone-Receptor-Positive Metastatic Breast Cancer Patients After Progression on Palbociclib

Abstract

Background: Despite the approval of mTOR inhibitor everolimus and CDK4/6 inhibitors in the management of hormone-receptor-positive HER2 non-amplified metastatic breast cancer (HR+ HER2-MBC), the optimal sequence of therapy is unclear. There are no clinical data on efficacy of everolimus in HR+ HER2-MBC after cancer progresses on CDK4/6 inhibitors. Objective: The objective of this study is to find the efficacy of everolimus in HR+ HER2-MBC after they progress on a CDK4/6 inhibitor palbociclib. Methods: This is a retrospective, 2-institute review of HR+ HER2-MBC from Jan 2015 to March 2018 treated with everolimus after progression on palbociclib. Primary end point was median progression-free survival (PFS), secondary end points objective response rate (ORR), clinical benefit ratio (CBR), and overall survival (OS). Results: Out of 41 women with median age 61 years (33, 87) enrolled, 66% had received adjuvant systemic therapy, 61% had visceral disease, and 95% had prior nonsteroidal aromatase inhibitors. About 83% women had 3 or more chemotherapy or hormonal therapies prior to everolimus. Kaplan-Meier estimates showed a median PFS of 4.2 months (95% confidence interval [CI]: 3.2-6.2). The median OS was 18.7 months (95% CI 9.5 to not reached). Objective response rate and CBR were both 17.1%. Conclusion: Everolimus was associated with modest PFS and ORR in HR+ HER2-MBCs postprogression on palbociclib.

Comparison of the Effectiveness and Clinical Outcome of Everolimus Followed by CDK4/6 Inhibitors with the Opposite Treatment Sequence in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer

“…Therefore, the survival outcomes of our study suggest that EVE-based regimens could be a reasonable choice after CDK4/6i failure, in which the optimal treatment strategies have yet to be established. These results are in line with prior retrospective studies that have reported similar PFS with EVE between CDK4/6i-exposed and unexposed patients [20], and a modest survival outcome with a median PFS of four months and a median OS of 19 months with EVE following CDK4/6i in a heavily treated patient population [21].…”

<p>Resistance and Overcoming Resistance in Breast Cancer</p>

“… 57 Furthermore, recent studies showed the benefit of everolimus with CDK4/6 inhibitor treatment in ER+ metastatic BC patients. 58 …”

Use of Real-World Evidence for Oncology Clinical Decision Making in Emerging Economies

“…A 2019 retrospective study demonstrated that first-, second-and third-line palbociclib treatment followed by subsequent hormonal therapy improved rw-PFS in patients with hormone receptor + and HER2-metastatic breast cancer [31]. In another study, Dhakal et al demonstrated that a treatment sequence of everolimus following palbociclib-progression (first, second, third and fourth line) led to improved rw-PFS [32]. RWE studies have also been conducted in emerging economies to better understand treatment sequencing.…”