Real life efficacy of palbociclib and endocrine therapy in HR positive, HER2 negative advanced breast cancer

Abstract

Background Palbociclib is indicated for the treatment of hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC), in combination with endocrine therapy. Emerging real-life data suggest that the efficacy of a palbociclib-based therapy is highly conserved. We report the Institut Curie hospital experience. Patients and methods We retrospectively reviewed all patients with HR + HER2- ABC treated with a palbociclib-based therapy as first or second line for ABC, with an initial prescription from November 2016 to December 2018. Clinical, laboratory and imaging data were retrieved from electronic records. Data lock was December 31st, 2019. Descriptive analyses, univariate and multivariate Cox regression analyses were performed. Results We included 310 consecutive patients. Median age was 61.8 years old. Palbociclib was prescribed in first line in 225 patients (72.6%). Before palbociclib-based therapy initiation, 122 patients (39.3%) were endocrine naive, 96 (31.0%) endocrine sensitive and 92 (29.7%) endocrine resistant. Median follow-up was 20.7 months. Median progression free survival (PFS) was 23.4 months (95%CI: 21.6-NR) in endocrine naive patients, 22.7 months (95%CI: 14.7-NR) in endocrine sensitive, and 13.4 months (95%CI: 10.7–20.8) in endocrine resistant. At 12 months from the initiation of palbociclib, 94.5% of patients were alive. By multivariate analysis, poor prognosis factors for PFS were identified in the endocrine naive/sensitive population: initial ECOG status 2, previous endocrine therapy for ABC, 3 metastatic sites or more. Toxicity profile was similar to previously published data. Conclusion In a non-selected population of patients with HR + HER2- ABC, the efficacy and safety data are strikingly similar to those previously reported.

Real-World Treatment Patterns and Clinical Effectiveness of Palbociclib Plus an Aromatase Inhibitor as First-Line Therapy in Advanced/Metastatic Breast Cancer: Analysis from the US Syapse Learning Health Network

“…Although the current study was conducted in a patient population distinct from that of the PALOMA-2 trial (i.e., patients in the current study were older, and more patients had only 1 metastatic site, bone-only disease, and de novo metastatic disease), the median rwPFS with first-line palbociclib plus an aromatase inhibitor observed herein (31.7 months) was complementary to the median PFS reported in PALOMA-2 (24.8 months) [ 9 , 11 ]. As mentioned previously, the higher median PFS reported in the present study may be attributed to a higher percentage of patients with bone-only disease and de novo metastatic disease at diagnosis [ 32 , 33 ]. While the reasons for the presence of a larger proportion of de novo A/MBC patients in our study population is unclear, we suspect that patients with de novo metastatic disease may be more likely to be treated with palbociclib plus an aromatase inhibitor, while patients who progressed to A/MBC may be more likely to be treated with palbociclib plus fulvestrant.…”

“…Previous real-world studies showed a median rwPFS between 15.1 and 37.9 months with palbociclib combination therapy as first-line therapy for HR+/HER2− A/MBC [ 19 , 26 , 27 , 28 , 29 , 30 ]. The median rwPFS outcome observed in the current real-world study is longer than some PFS estimates previously reported; this may be due in part to the better overall prognostic characteristics of the patients in this cohort, with a larger proportion of patients with de novo disease and bone-only disease, which tends to be associated with longer PFS [ 32 ]. In addition, nuances in rwPFS between studies may also be due to differences in median duration of follow-up; some real-world studies reported between 9.9 and 10.8 months of follow-up [ 20 , 26 , 28 ].…”

Real‐world benefit of combination palbociclib and endocrine therapy for metastatic breast cancer and correlation with neutropenia

“…33 Finally, a more recent study by Porte et al reported similar median PFS in unselected patients who received palbociclib and endocrine therapy compared with published clinical trial data. 34 We posit that the survival benefit of neutropenia is likely due to the suppression of pro-tumor effects by neutrophils. Angiogenesis is mediated through degradation of the extracellular matrix by matrix metalloproteinase 9 (MMP-9), which then causes release of potent angiogenic factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2).…”

“… 33 Finally, a more recent study by Porte et al reported similar median PFS in unselected patients who received palbociclib and endocrine therapy compared with published clinical trial data. 34 …”

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2–advanced breast cancer: GEICAM/2014–12 (FLIPPER)

“…The results are reassuring for considering CDK4/6i combined with endocrine therapy as upfront treatment for the majority of patients with HR positive/HER2 negative ABC. Two recent systematic reviews and meta-analysis support the superiority of CDK4/6i plus endocrine therapy over endocrine therapy alone in the vast majority of patients [22,23]. The authors also noted that in selected patients with low tumor burden and indolent endocrine-sensitive disease, particularly those with only-bone and very limited disease, endocrine therapy alone might still remain a valid option [22,23].…”