Real-world safety of palbociclib in breast cancer patients in the United States: a new user cohort study

Abstract

Background There is limited real-world safety information on palbociclib for treatment of advanced stage HR+/HER2- breast cancer. Methods We 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. Results There 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). Conclusions This 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).

Outcome in patients of hormone receptor (HR) positive (Her 2) negative metastatic breast cancer treated with palbociclib – A real-world experience

“…[5] The PFS and toxicity analysis results are consistent with other reports of routine clinical practice, that is, real-world evidence from India and other countries and the global clinical trials. [6][7][8][9][10][11][12][13][14][15][16][17] The observed OS is lower than reported in real-world studies and clinical trials. Our analysis suggests that patients who were less heavily pre-treated had better outcomes.…”

“…The safety profile of palbociclib was consistent with that seen in clinical practice and trials in India and other countries. [6,[10][11][12]15,16] The major limitation of our study is its retrospective nature as that introduces a potential bias in patient selection, also it being a single-institutional single-arm study with a small sample size.…”

New Insights on the Toxicity on Heart and Vessels of Breast Cancer Therapies

“…In several trials, those drugs have demonstrated positive outcomes in terms of survival [114][115][116]. The most common adverse effect of this drug is bone marrow suppression and, consequently, pancytopenia [117,118]. The CV concerns for the toxicity of this class of drugs is principally due to the possible effect of ribociclib prolonging the QT interval.…”

Challenges and Opportunities With Routinely Collected Data on the Utilization of Cancer Medicines. Perspectives From Health Authority Personnel Across 18 European Countries

“…Various regulatory mechanisms have also been introduced including adaptive licensing ( Eichler et al, 2012 ; Eichler et al, 2015 ; Vella Bonanno et al, 2017 ), accelerated assessments and conditional marketing approval, to facilitate authorization and funding of promising candidate medicines early in their development ( Hoekman et al, 2015 ; Martinalbo et al, 2016 ). However, there are concerns with such proposals due to the lack of robust evidence for improved outcomes of these new medicines when used in routine clinical practice ( Godman et al, 2014a ; Beachler et al, 2021 ). In addition, currently new oncology treatments are often evaluated based on Phase II and III trials using surrogate endpoints, which are easier to measure ( Kim and Prasad, 2015 ; Kemp and Prasad, 2017 ).…”

“…Real-world data collected in routine care can derive from a number of sources including hospital and pharmacy registers, electronic health records, administrative datasets, patient registers as well as population and healthcare surveys ( OECD Health Division, 2019 ). Such data can complement RCTs to help assess the effectiveness of new medicines in routine clinical care versus their documented efficacy in trials ( Khor et al, 2014 ; Kibbelaar et al, 2017 ; Kilburn et al, 2017 ; Zanotti et al, 2017 ; Eriksson et al, 2018 ; Baillie et al, 2020 ; Lemanska et al, 2020 ; Beachler et al, 2021 ; Lester et al, 2021 ; Nakayama et al, 2021 ). Real-world data has for instance been used in the evaluation of real-world outcomes of olaparib treatment for ovarian cancer in Sweden ( Eriksson et al, 2018 ).…”