CLINICAL AND PHARMACOECONOMIC ANALYSES OF CDK4/6 INHIBITORS USE IN STAGE IV BREAST CANCER FEMALES IN THE STATE OF QATAR: A COMPARATIVE RETROSPECTIVE OBSERVATIONAL STUDY WITH COST-EFFECTIVENESS AND COST-UTILITY ANALYSES

Abstract

Introduction: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are indicated in the first-line treatment of hormonal receptor positive and HER-2 negative (HR+/HER2- negative) advanced breast cancer. Although phase III randomized controlled trials (RCTs) proved their clinical efficacy, they can increase healthcare expenditure. To date, there are no observational studies to validate the clinical findings of the existed RCTs. In addition, only a few pharmacoeconomic evaluations were published regarding the two common CDK4/6 inhibiting agents, palbociclib and ribociclib to evaluate their financial burden. Objectives: To evaluate the clinical efficacy of palbociclib and ribociclib in the local settings in Qatar. Moreover, to conduct a thorough pharmacoeconomic analysis for the two medications and compare them in terms of their cost-effectiveness and cost-utility. Methodology: A retrospective observational study on HR+/HER-2 negative stage IV breast cancer patients receiving palbociclib or ribociclib in Qatar was conducted, followed by a comparative pharmacoeconomic analysis. Clinical data were collected from the National Center for Cancer Care and Research (NCCCR) from January 2017 to December 2019 using Cerner system. The primary outcomes were progression-free survival (PFS) and overall-survival (OS) generated by Kaplan Meier curves. Safety profiles of both of the two medications were also evaluated. Then, a thorough cost- analysis was conducted by accounting methodology to summarize the overall cost of the treatment strategies of palbociclib and ribociclib. Costs were obtained from the department of accounting and finance in the NCCCR. To evaluate the long-term costs and effectiveness, a 10-year within-cycle corrected Markov's model was developed. The Markov's model consisted of three main health states: progression-free (PFS), progressed disease (PD), and death. Costs were summarized from the cost-analysis, transition probabilities were calculated from individual patient data obtained in the clinical phase, and utilities were summarized from the published literature. Incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) were compared to a three gross-domestic-product (3 GDP) per capita. Deterministic and probabilistic sensitivity analyses were carried out. Modeling was conducted via TreeAge Pro software. Results: There was no statistically significant difference between the palbociclib and ribociclib groups in terms of PFS; median PFS time was 17.85 versus 13.55 months respectively; p> 0.05. Similarly, there was no statistically significant difference in terms of OS between the two medications 29.82 versus 31.72 months; p>0.05. For the pharmacoeconomic analysis, ribociclib dominated palbociclib in yielding an ICER of -83,090.88 QAR per life year gained, and ICUR of -31,868.06 QAR per quality-adjusted life year gained. The results remained robust in all cases of the deterministic sensitivity analyses suggesting ribociclib is more cost-effective than palbociclib. Taking all combined uncertainties into account, the overall confidence in the base-case conclusion was around 60%. Conclusions: Both treatment strategies have similar efficacy and safety profiles. Nonetheless, ribociclib is a more cost-effective option than palbociclib based on the base-case results and based on the addressed uncertainties related to the model inputs.