Abstract

BackgroundRecent approvals of second-generation androgen receptor inhibitors (SGARIs) have changed the treatment landscape for non-metastatic castration-resistant prostate cancer (nmCRPC). These SGARIs have similar efficacy but differ in safety profiles. We used a discrete choice experiment to explore how United States physicians make treatment decisions between adverse events (AEs) and survival gains in nmCRPC, a largely asymptomatic disease.MethodsTreating physicians (n = 149) participated in an online survey that included 14 treatment choice questions, each comparing 2 hypothetical treatment profiles, which varied in terms of 5 safety and 2 efficacy attributes. We described safety attributes (fatigue, skin rash, cognitive problems, falls, and fractures) in terms of severity and frequency, and efficacy attributes (overall survival [OS] and time to pain progression) in terms of duration of effect. We used a random parameters logit model to estimate preference weights and importance scores for each attribute. We also estimated the amount of survival gain physicians were willing to trade for a reduction in specific AEs between treatment options.ResultsPhysicians placed more importance on survival than on time to pain progression, and viewed a reduction in cognitive problems from severe to none, a reduction in risk of a serious fracture from 8% to none, and a reduction in fatigue from severe to none as the most important safety attributes. Physicians were willing to forego 9.1 and 6.6 months of OS, respectively, to reduce cognitive problems and fatigue from severe to mild-to-moderate. To reduce the risk of a serious fracture from 8 to 5% and 5% to none, physicians were willing to trade 3.9 and 5.3 months of OS, respectively.ConclusionsPhysicians were willing to trade substantial amounts of survival to avoid AEs between hypothetical treatments. These results emphasize the importance of carefully balancing therapies’ benefits and risks to ultimately optimize the overall quality of nmCRPC patients’ survival. Nonetheless, it is noted that the results from the study sample of 149 physicans may not be representative of the viewpoints of all nmCRPC-treating physicians.

Highlights

  • Recent approvals of second-generation androgen receptor inhibitors (SGARIs) have changed the treatment landscape for non-metastatic castration-resistant prostate cancer

  • By using a formal discrete choice experiment (DCE) approach following recommended practices [20, 21], we aimed to quantify the benefit-risk preferences that United States (US) practicing physicians associate with non-metastatic castration-resistant prostate cancer (nmCRPC) and Second-generation androgen receptor inhibitor (SGARI) therapy, and examine the extent to which physicians are willing to trade their nmCRPC patients’ overall survival (OS), to minimize or avoid Adverse event (AE) of interest

  • This research focused on OS instead of metastasis-free survival (MFS) because the MFS definition varies slightly between trials and is a fairly recent endpoint, whereas OS is assumed to be universally understood by most physicians

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Summary

Introduction

Recent approvals of second-generation androgen receptor inhibitors (SGARIs) have changed the treatment landscape for non-metastatic castration-resistant prostate cancer (nmCRPC). These SGARIs have similar efficacy but differ in safety profiles. Non-metastatic castration-resistant prostate cancer (nmCRPC) is characterized by biochemical progression (i.e., rising prostate-specific antigen [PSA] after androgen deprivation therapy (ADT) without evidence of detectable disease on conventional imaging [1]. The relative lack of evidence on these strategies’ benefits presents a challenge to clinicians making treatment recommendations [5] This can be further complicated by patients requesting treatment upon experiencing anxiety due to rising PSA levels [6, 7]

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