Abstract PS10-40: Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer
Authors: Porte Baptiste , Carton Matthieu , Loirat Delphine , Bidard François-Clement , Haroun Linda , Bellesoeur Audrey , Kirova Youlia , Cottu Paul 
Published: February 2021

Abstract
BackgroundPalbociclib, a highly selective inhibitor of CDK4/6, is indicated for the treatment of hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC), in combination with an aromatase inhibitor or with fulvestrant for patients who have progressed with an aromatase inhibitor, and in premenopausal women with a luteinising-hormone-releasing-hormone (LH-RH) agonist. Emerging real world data suggest that the efficacy of a palbociclib-based therapy is highly conserved. We report here the Institut Curie (IC) experience.
Patients and methodsWe retrospectively reviewed all patients with HR+ HER2- ABC treated with a palbociclib-based therapy as 1st or 2nd line of therapy for ABC, from November 2016 to December 2018. Clinical, biological and imaging data were retrieved from IC electronic health record system. Data lock was December 31st 2020. Descriptive analyses, univariate and multivariate Cox regression analyses were performed.
ResultsWe included 310 consecutive premenopausal (24.5%) and menopausal (75.5%) women. Median age was 61.8 years-old [23.5-92.1]. Among them, Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 59.7%, 1 in 32.1%, and 2 in 8.2% of patients (pts). The ABC diagnosis was de novo for 26.8%. There was at least one visceral lesion in 51.0% of pts, only bone lesions in 30.3%, 28.1% had three metastatic sites or more, and none of them have brain lesions. Previous treatments were chemotherapy (49.4%) and endocrine therapy (60.7%). Among pts pretreated by at least one endocrine therapy, 51.1% had shown prior sensibility, as defined by an absence of recurrence during adjuvant endocrine therapy or during 24 months after its completion, or an absence of progression during 6 months after the beginning of an endocrine therapy for a metastatic disease. Palbociclib was prescribed in the 1st line setting for 72.6% of pts and in the 2nd line setting for 27.4% of pts. The initial dose was 125 mg daily (95.2%). It was associated with an aromatase inhibitor (66.8%) or with fulvestrant (33.2%). LH-RH agonist was prescribed in 19.7% of pts. Denosumab was prescribed in 68.5% of pts with bone lesions. Median follow-up was 20.7 months (m). At 12 m from the initiation of palbociclib, 94.5% of the pts were alive. Median progression free survival was 23.4 m (95%CI: 21.6-NR) for pts without previous endocrine therapy, 22.7 m (95%CI: 14.7-NR) for pts who have shown endocrine sensibility, HR=1.2 (95%CI: 0.81-1.77), p=0.0027 and 13.4 m (95%CI: 10.7-20.8) for pts who have not shown endocrine sensibility, HR=1.88 (95%CI: 1.29-2.73), p=0.003. Although sensibility to previous endocrine therapy was a prognostic factor for progression free survival with the univariate analyse, it was not with the multivariate analysis. Three independent poor prognostic factors for progression free survival were identified: previous chemotherapy, HR=1.6 (95%CI: 1.12-2.29), p&lt;0.001; initial ECOG performance status 2, HR=2.72 (95%CI: 1.55-4.79), p&lt;0.001; and three or more metastatic sites, HR=1.61 (95%CI: 1.152.26), p&lt;0.001. Hematologic grade 3-4 adverse events were neutropenia (72.3%), leukopenia (43.9%), anemia (3.2%) and thrombocytopenia (2.9%). Other adverse events observed (all grades) were infections (16.5%), stomatitis (13.9%) or alopecia (13.9%). At least one dose reduction occurred in 29.4% of pts and permanent discontinuation because of treatment toxicity was observed in 5.7% of pts.
ConclusionIn a non-selected population of patients with HR+ HER2- ABC, the efficacy and safety data are strikingly similar to those previously reported. Palbociclib, in combination with hormone therapy, is a cornerstone treatment of HR+ HER2- metastatic breast cancer.
Citation Format: Baptiste Porte, Matthieu Carton, Delphine Loirat, François-Clement Bidard, Linda Haroun, Audrey Bellesoeur, Youlia Kirova, Paul Cottu. Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer [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 PS10-40.