Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study

Abstract

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. Patients and methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47–79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6–32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2− MBC, also suggesting a better performance of the combinations in earlier treatment lines.

First-Line Treatment with a Cyclin-Dependent Kinase 4/6 Inhibitor Plus an Aromatase Inhibitor for Metastatic Breast Cancer in Alberta

“…While median OS in our cohort has not yet been reached, OS at 3 years was 68%. This result is comparable to OS at 3 years for the palbociclib + letrozole cohort from the Flatiron database (72%) [ 20 ] and superior to a historical Alberta cohort of de novo HR-positive, HER2-negative MBC patients aged <65 years who were diagnosed 1 January 2010 through 31 December 2014 and would not have had access to a CDK4/6i in the first-line setting (56%) [ 27 ]. In terms of the pivotal RCTs of CDK4/6 inhibitors + AI, only Monaleesa-7 (all pre-menopausal patients with ovarian function suppression) reported OS, which was significantly better in the ribociclib arm (OS at 42 months, 70% vs. 46%; HR, 0.71, 95% CI, 0.54–0.95) [ 28 ].…”

“…Median PFS was 24.7 vs. 16.6 months in favour of combination treatment, but the difference was not statistically significant, with an adjusted hazard ratio (HR) of 0.87 (95% CI, 0.58–1.32), probably reflecting the small sample size of the study. Other prospective real-world studies have now been published, including a multicentre cohort from northern Italy [ 20 ]. Of the 182 patients included in the primary analysis, 61 (33.5%) received palbociclib plus an AI or fulvestrant in the first-line setting.…”

Real-world effectiveness of palbociclib plus fulvestrant in advanced breast cancer: Results from a population-based cohort study

“…With a median follow-up of 10.2 months, median PFS was estimated at 10.3 months (95%CI 8.16–12.3) [ 35 ]. More recently, a study conducted in Italy including 92 patients and having a median follow-up time of 24 months found a median PFS of 12.2 months (95%CI 3.0–19.0) [ 36 ]. Although our estimates [median rwPFS 7.43 months (95%CI 6.28–9.05) and median rwOS 24.70 months (95%CI 21.58–29.27)] are consistently inferior to the above-mentioned studies, it should be noticed that the comparison is challenging due to the limited follow-up duration of these studies, absence of data for OS in some of them, different healthcare settings as well as imprecision of the results obtained for these studies, as exposed by the wider confidence intervals reported.…”

Palbociclib plus endocrine therapy significantly enhances overall survival of HR+/HER2− metastatic breast cancer patients compared to endocrine therapy alone in the second‐line setting: A large institutional study

“…21 After the PALOMA clinical trials, several published real-world data on the safety and effectiveness of the CDK4/6 inhibitors + ET in routine clinical practice have collectively, shown similar efficacy and safety profiles to the clinical trials. [30][31][32][33][34][35][36] However, these reports were limited in scope due to the heterogenous follow-up practices observed across different institutions; some studies had small sample sizes or lack of a proper "control" cohort. To overcome these limitations, the goal in our study is to provide evidence from a single institution, the MD Anderson Cancer Center (MDACC), for both PFS and OS of palbociclib + ET using a comprehensively annotated and curated database and comparing the outcome data to the historical controls using propensity-matched patients who received ET alone in both first-line and second-line settings.…”

“…After the PALOMA clinical trials, several published real‐world data on the safety and effectiveness of the CDK4/6 inhibitors + ET in routine clinical practice have collectively, shown similar efficacy and safety profiles to the clinical trials 30‐36 . However, these reports were limited in scope due to the heterogenous follow‐up practices observed across different institutions; some studies had small sample sizes or lack of a proper “control” cohort.…”