Abstract P3-01-07: Phase II trial of palbociclib with fulvestrant in individuals with hormone receptor-positive, HER2-negative metastatic breast cancer with disease progression after palbociclib with an aromatase inhibitor
Authors: Tao Jessica J. , Blackford Amanda L. , Nunes Raquel , Truica Cristina I. , Mahosky Justin , Jones Mary Kate , Leasure Nick C. , Cescon Terrence , Christou Antonios , Werner Jeanine L. , Couzi Rima , Smith Karen L. , Santa-Maria Cesar Augusto , Wolff Antonio C. , Stearns Vered 
Published: March 2023

Abstract
Background: CDK4/6 inhibition (CDK4/6i) with endocrine therapy (ET) is a standard first line treatment for individuals with HR+, HER2- metastatic breast cancer (MBC). The anti-proliferative effect of CDK4/6i may reverse upon discontinuation, and the role of continuing CDK4/6i after progression on a CDK4/6i with aromatase inhibitor (AI) is not known. We examine the clinical activity of palbociclib and fulvestrant after disease progression on palbociclib with AI in a phase II trial in individuals with HR+, HER2- MBC (NCT02738866).
Methods: We conducted a prospective, phase II, multicenter, open-label study of palbociclib with fulvestrant in patients with HR+ HER2- MBC with disease progression after at least 6 months of first line palbociclib and AI. Previous chemotherapy was allowed. Eligible participants received fulvestrant and continued on the same palbociclib dose. Premenopausal women received a concomitant GnRH agonist. We obtained a baseline tumor biopsy, when accessible, for correlative studies, and serial blood samples for ctDNA and circulating tumor cells (CTCs) analysis. Participants received disease assessment with imaging every 2 cycles (8 weeks) for the first year, followed by every 3 cycles (12 weeks) for participants who had been on study for &gt;12 months. The primary endpoint was progression-free survival (PFS), estimated using the Kaplan Meier method. Other key endpoints included objective response rate (ORR) and clinical benefit rate (CBR) per RECIST v1.1.
Results: As of June 1, 2022, a total of 58 of 60 participants were enrolled, with median age 57.9 (range 28.2-82.1 years). 17 patients (29%) were premenopausal. 41 (71%) of participants were white and 12 (21%) of participants were black/African American. Median PFS (mPFS) among the entire cohort was 3.7 months; among pre-menopausal patients, mPFS was 2.5 months and among post-menopausal patients, mPFS was 4.0 months). 22 (38%) of patients were on treatment for 6 or more months, with 11 (19%) of patients experiencing long term response beyond one year (Table 1). 13/58 (22%) of participants required further dose reductions of palbociclib after initiating fulvestrant despite previously being on a stable dose of palbociclib with an AI; no unexpected treatment-related toxicities were noted. Updated results for the entire 60 patient cohort will be presented at the meeting.
Conclusions: Second line ET with palbociclib and fulvestrant following palbociclib and AI resulted in limited overall PFS. However, 38% of participants remained on therapy for greater than 6 months, suggesting clinical benefit in a subset of participants. Correlative studies, including of tissue, serial ctDNA and CTCs, are ongoing to further characterize this subset.
Table 1: Preliminary efficacy of palbociclib and fulvestrant
Citation Format: Jessica J. Tao, Amanda L. Blackford, Raquel Nunes, Cristina I. Truica, Justin Mahosky, Mary Kate Jones, Nick C. Leasure, Terrence Cescon, Antonios Christou, Jeanine L. Werner, Rima Couzi, Karen L. Smith, Cesar Augusto Santa-Maria, Antonio C. Wolff, Vered Stearns. Phase II trial of palbociclib with fulvestrant in individuals with hormone receptor-positive, HER2-negative metastatic breast cancer with disease progression after palbociclib with an aromatase inhibitor [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-07.