Abstract
Purpose
Several adjuvant phase III trials are evaluating cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) in combination with endocrine therapy (ET) in hormonal receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer (eBC). This study examines preferences for this combination regimen and ET alone among patients, oncologists, and payers in the United States.
Methods
A web-based questionnaire, including a discrete choice experiment (DCE), was administered to patients, practicing oncologists, and payers. In the DCE, respondents selected between hypothetical treatment profiles with attributes associated with ET monotherapy and CDK4/6i + ET regimens. Each treatment alternative was defined by the following attributes: 5-year invasive disease-free survival (iDFS), nausea, diarrhea, neutropenia, alopecia, dosing schedule, and electrocardiogram (ECG) monitoring. Payers had the additional attribute of annual per-patient treatment cost. Hierarchical Bayesian models were used to estimate relative preference weights for each attribute-level and relative attribute importance.
Results
For patients (n=300) and oncologists (n=200), iDFS was most important (2 to 3 times more important than the next most important attribute), followed by neutropenia and diarrhea risks for patients and oncologists, respectively. Patients and oncologists required an improvement in iDFS of 8.0 and 5.6 percentage-points, respectively, to accept an increase in diarrhea risk from 11% to 81%. Payers (n=60) viewed annual per-patient cost as most important for treatment access decision-making, closely followed by iDFS. Payers required an improvement in iDFS of 21.8 percentage-points to accept an increase in cost from $5,100 to $149,400. Across all stakeholder groups, dosing schedule, alopecia risk, and ECG monitoring were perceived as least important.
Conclusion
Patients, oncologists, and payers expect a large absolute risk reduction in efficacy to offset the potential risks and costs of adding a CDK4/6i to current standard of care. An open discussion between all stakeholders is necessary to ensure that decision-making, whether at patient- or system-level, is informed by preferences for novel treatments, like CDK4/6is.
Abbreviations
AI, aromatase inhibitor; AJCC, American Joint Committee on Cancer; BC, breast cancer; CDK4/6i, cyclin-dependent 4/6 kinase inhibitor; CI, confidence interval; DCE, discrete choice experiment; eBC, early-stage breast cancer; ECG, electrocardiogram; ET, endocrine therapy; G, grade; GI, gastrointestinal; HER2-, human epidermal growth factor receptor 2 negative; HR+, hormone receptor positive; iDFS, invasive disease-free survival; IDN, integrated delivery network; IQR, interquartile range; ISPOR, International Society of Pharmacoeconomic and Outcomes Research; MCO, managed care organization; NCCN, National Comprehensive Cancer Network; P&T, pharmacy and therapeutics; PBM, pharmacy benefits manager; PO, orally; QD, daily; SD, standard deviation; SVP, senior vice president; US, United States; VP, vice president.
Data Sharing Statement
Upon request, and subject to certain criteria, conditions, and exceptions (see https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual de-identified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines, and medical devices (1) for indications that have been approved in the US and/or EU or (2) in programs that have been terminated (ie, development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer trials 24 months after study completion. The de-identified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer.
Acknowledgments
We would like to thank Dr. Ann-Marie Waldron (Kantar Health GmbH, Munich) for medical writing assistance, which was funded by Pfizer. A portion of the results reported on in this manuscript was presented at the European Society for Medical Oncology (ESMO) Annual Congress, which was held virtually on September 19–21, 2020, and was presented at the Academy of Managed Care Pharmacy (AMCP) Nexus Conference, which was held virtually on October 20–23, 2020.
Author Contributions
All authors contributed to data analysis or interpretation of the data, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
Disclosure
KB, BH, MMG, and MCM are employees of Kantar, which received funding from Pfizer Inc to conduct and report on the study; EHL is an employee and stockholder of Pfizer Inc; MLS is part of the advisory board for Pfizer and an advisor for Novartis. The authors report no other conflicts of interest in this work.