Abstract PS12-25: Patterns of treatment and outcomes in real world patients with advanced estrogen receptor positive breast cancer receiving palbociclib and endocrine therapy
Authors: Prior Lisa , Skrobo Darko , Murray Hazel , Farooq Abdul Rehman , Horgan Anne , Calvert Paula , Jordan Emmet , McCaffrey John , Smyth Lillian , O'Connor Miriam , Higgins Michaela , Carney Desmond , Walshe Janice , Gullo Giuseppe , Crown John , Kelly Catherine M 
Published: February 2021

Abstract
Background: Advancement in the treatment of metastatic estrogen receptor positive (ER+) breast cancer has led to the introduction of CDK4/6 inhibitors such as Palbociclib, which are associated with reversal of endocrine resistance and delayed requirement for chemotherapy. Clinical trials to date have demonstrated improved survival outcomes for patients on these agents. The objective of this study was to evaluate their role in a real-world setting.
Methods: We performed a retrospective multicentre analysis of patients (pts) with metastatic ER+ breast cancer who were commenced on Palbociclib (PAL) between January 2010 and September 2019. Data extracted included demographics, disease characteristics, treatments, toxicities, response rates and survival outcomes. Statistical analysis was performed using Cox proportional hazard model for univariate analysis and Kaplan Meier curves for survival data.
Results: We identified 271 pts. The median age was 60 years (31-88) and 18% (n=48) pts were premenopausal. PAL was combined with the following ET partners: Aromatase inhibitor (AI) (38%, n=103), Fulvestrant (FUL) (38%; n=103), Tamoxifen (4%, n=10), FUL & AI combination (16%, n=44) and other (4%, n=11). Among 71 pts treated in the 1st line, overall response rate (ORR) was 56% (n=40). The median PFS (progression free survival) was 35 months (95% confidence interval [CI], 17.2-52.7) in all pts and 25 months (mo) in those not treated with FUL. In 1st line pts with de novo disease (37%, n=26), there appeared to be a trend towards improved PFS in the FUL vs non FUL group - not reached vs 25 mo (HR 0.21; 95% CI 0.02-1.79, p=0.15). There was no significant difference in PFS between the FUL vs non FUL group in relapsed pts (63%, n=45) treated in the 1st line - 22 vs 20 mo (HR 1.0, 95%CI 0.35-2.9; p=0.96). The median OS was 59 mo (95% CI, 9.5 to 108). Of 74 pts treated in the 2nd line, ORR was 24% (n=18), median PFS was 10 mo (95% CI, 5.8-14.1) & OS was 25 mo (95% CI, 18.3-31.6). Among 126 3rd line pts, ORR was 16% (n=20), median PFS was 5 mo (95% CI, 3.5-6.4) and OS was 20 mo (95% CI, 12.8-27.1). 3 of 9 pts achieved &gt;6 mo of stable disease after switching ET and continuing Palbociclib beyond progression. The most frequent grade 3 toxicities were neutropenia (40%), anaemia (4%), fatigue (3%) & thrombocytopenia (2.5%). The rate of febrile neutropenia was 2.5%. Dose reductions occurred in 40%, with the most common reason being neutropenia. Treatment was discontinued in 3% due to toxicity. Premenopausal status or dose reductions were not associated with poorer survival outcomes.
Conclusions: Palbociclib appears to be safe and tolerable in a real-world population and is associated with favourable survival outcomes comparable to that seen in a clinical trial setting. Combining Palbociclib with Fulvestrant as opposed to other endocrine therapies may delay progression in the 1st line setting in patients with de novo metastatic ER+ breast cancer but larger studies are needed to explore this hypothesis further.
Citation Format: Lisa Prior, Darko Skrobo, Hazel Murray, Abdul Rehman Farooq, Anne Horgan, Paula Calvert, Emmet Jordan, John McCaffrey, Lillian Smyth, Miriam O'Connor, Michaela Higgins, Desmond Carney, Janice Walshe, Giuseppe Gullo, John Crown, Catherine M Kelly. Patterns of treatment and outcomes in real world patients with advanced estrogen receptor positive breast cancer receiving palbociclib and endocrine therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-25.