Patient-reported outcomes for patients with metastatic castration-resistant prostate cancer receiving docetaxel and Atrasentan versus docetaxel and placebo in a randomized phase III clinical trial (SWOG S0421)

Joseph M Unger,Iii Iii,Maha Hussain,David I Quinn,James L Wade,Michael A Carducci,Eunicia Reburiano,Margorie J Good,Catherine M Tangen,Ian M Thompson,Paul Monk ,Celestia S Higano,Peter J Van Veldhuizen,Jr ,Karen Baranowski ,Gary Donaldson ,Primo N Lara,Nicholas J Vogelzang,Katie Griffin ,Carol M Moinpour

doi:10.1186/s41687-018-0054-5

Abstract

BackgroundSWOG S0421 was a large randomized trial comparing docetaxel/prednisone plus placebo (DPP) to docetaxel/prednisone plus atrasentan over 12 cycles for patients with metastatic castration-resistant prostate cancer (mCRPC). The current report presents the PRO results for this trial, an important secondary endpoint.MethodsThe trial specified two primary PRO endpoints. Palliation of worst pain was based on the Brief Pain Inventory (BPI), where a 2 point difference is defined as clinically meaningful. Improvement of functional status was based on the Functional Assessment of Cancer Therapy – Prostate Cancer Trial Outcome Index (FACT-P TOI); a 5-point difference has been defined as clinically meaningful. We compared rates by arm using chi-square tests. Longitudinal analyses using linear mixed models addressed changes by arm over time.ResultsFour-hundred eighty-nine patients on each arm were evaluable for PRO endpoint data. There were no differences by arm in clinically meaningful pain palliation (41.7% for DPP vs. 44.0% for DPA, p = .70) or functional status (24.2% for DPP vs. 28.7% for DPA, p = .13). Longitudinal comparisons indicated no differences over time by arm for BPI Worst Pain scores (0.13 points, p = .23). Patients on the DPA arm had improved functional status of 1.78 points on average, a statistically significant (p = .02) but not clinically meaningful difference.ConclusionsThe SWOG S0421 PRO data showed little evidence of clinically meaningful differences by arm in either pain palliation or functional status.

Highlights

SWOG S0421 was a large randomized trial comparing docetaxel/prednisone plus placebo (DPP) to docetaxel/prednisone plus atrasentan over 12 cycles for patients with metastatic castration-resistant prostate cancer
Patient population and study design SWOG S0421 was activated in August, 2006 and closed in May, 2010
The this study had 89% power to detect a 15% difference in the proportion of pain palliated patients (e.g., 35% versus 50%) using a two-sided test, based on the hypothesis was that worst pain reduction would be at least 15% more in the in the DPA arm compared to the DPP arm

Summary

Introduction

SWOG S0421 was a large randomized trial comparing docetaxel/prednisone plus placebo (DPP) to docetaxel/prednisone plus atrasentan over 12 cycles for patients with metastatic castration-resistant prostate cancer (mCRPC). Patients with metastatic castration-resistant prostate cancer (mCRPC) are no longer sensitive to a continued regimen of androgen deprivation treatment (ADT). This condition is defined based on confirmed objective progression and/or increases in prostate specific antigen (PSA) in the presence of castrate ranges of testosterone; bone metastases are often present. The inclusion of Patient-Reported Outcomes (PROs) in studies of prostate cancer are vital for informing trial interpretations, as they provide key insights into patients’ symptoms and treatment response [2]. Men with prostate cancer face issues that differ substantially depending on stage of disease; early stage patients receiving local treatment to the prostate experience urinary, sexual, and bowel problems, while men in the advanced care setting experience systemic bone pain and symptomatic deterioration [3]. In mCRPC trials, PROs can be especially useful for informing the assessment of the risk/benefit tradeoff from the patient’s perspective for treatment regimens with modest effects on overall survival [6, 7]

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Conclusion