Abstract
BackgroundThere is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer.MethodsWe conducted a cohort study of breast cancer patients initiating palbociclib and fulvestrant from February 2015 to September 2017 using the HealthCore Integrated Research Database (HIRD), a longitudinal claims database of commercial health plan members in the United States.The historical comparator cohort comprised patients initiating fulvestrant monotherapy from January 2011 to January 2015. Propensity score matching and Cox regression were used to estimate hazard ratios for various safety events. For acute liver injury (ALI), additional analyses and medical record validation were conducted.ResultsThere were 2445 patients who initiated palbociclib including 566 new users of palbociclib-fulvestrant, and 2316 historical new users of fulvestrant monotherapy. Compared to these historical new users of fulvestrant monotherapy, new users of palbociclib-fulvestrant had a greater than 2-fold elevated risk for neutropenia, leukopenia, thrombocytopenia, stomatitis and mucositis, and ALI. Incidence of anemia and QT prolongation were more weakly associated, and incidences of serious infections and pulmonary embolism were similar between groups after propensity score matching. After adjustment for additional ALI risk factors, the elevated risk of ALI in new users of palbociclib-fulvestrant persisted (e.g. primary ALI algorithm hazard ratio (HR) = 3.0, 95% confidence interval (CI) = 1.1–8.4).ConclusionsThis real-world study found increased risks of several adverse events identified in clinical trials, including neutropenia, leukopenia, and thrombocytopenia, but no increased risk of serious infections or pulmonary embolism when comparing new users of palbociclib-fulvestrant to fulvestrant monotherapy. We observed an increased risk of ALI, extending clinical trial findings of significant imbalances in grade 3/4 elevations of alanine aminotransferase (ALT).
Highlights
There is limited real-world safety information on palbociclib for treatment of advanced stage Hazard ratio (HR)+/ Human epidermal growth factor receptor 2 (HER2)- breast cancer
We developed a more sensitive acute liver injury (ALI) algorithm that included a broader set of codes in both inpatient and outpatient settings [5, 7], and a more specific ALI algorithm restricting to primary inpatient codes that had a high Positive predictive value (PPV) in the Mini-Sentinel validation study [5]
We examined the potential effect of unmeasured confounding by calculating the E-value (the associations between the confounder-exposure and the confounder-outcome needed to attenuate the association of interest to a level indicating no effect (HR) =
Summary
There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/ HER2- breast cancer. In February 2016, palbociclib in combination with fulvestrant received US approval for the treatment of women with HR+/HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy [1]. Some of the most commonly occurring (> 10%) AEs in the palbociclib arms of the trials included neutropenia, infections, leukopenia, and anemia [2, 3] These trials revealed an increased risk of grade 3/4 elevations of alanine aminotransferase (ALT), with palbociclib – but were limited in size and breast cancer disease severity in evaluating less common AEs such as acute liver injury (ALI) [1,2,3]. Based on the initial results, further analyses were conducted to further assess ALI and to validate ALI using medical records
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
