Integrated analysis of pain, health-related quality of life, and analgesic use in patients with metastatic castration-resistant prostate cancer treated with Radium-223

Sushil K Badrising ,Jeantine M De Feijter,Vincent O Dezentjé,Hanneke Zuetenhorst,Suzan Ras-Van Spijk,Rebecca D Louhanepessy,Filiz Dadaşer-Çelik ,Wilbert Zwart,John B.a.g Haanen ,Erik Vegt,Marnix G E H Lam ,Jacobien M Kieffer ,Ad H J Oostdijk ,Lonneke V Van De Poll‐Franse ,Vincent Van Der Noort,Jules L.l.m Coenen ,Nils Wagenaar,Olaf Loosveld ,Aart Beeker,Paul Hamberg,Andries M Bergman

doi:10.1038/s41391-021-00412-6

Abstract

BackgroundRadium-223 (Ra-223), an alpha-emitting radiopharmaceutical, established an improved overall survival and health-related quality of life (HRQoL) in symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients. However, effects on pain were not specifically evaluated. Here we assess integrated HRQoL, pain, and opioid use in a contemporary, more extensively pretreated, symptomatic and asymptomatic mCRPC population.MethodsmCRPC patients scheduled for Ra-223 treatment were included and analyzed for HRQoL, pain, and opioid use, using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory-Short Form (BPI-SF) questionnaires and recording of opioid use and dosage, respectively. Primary outcome measure was the percentage of patients experiencing a complete pain response (score of 0 on the BPI-SF Worst pain item and no increase in daily use of analgesics). A complete or partial pain response (better BPI-SF score and decrease in opioid use) and a better or no change in HRQoL was evaluated as an integrated overall clinical response (IOCR). Secondary endpoints included the time to pain progression (TPP) and Total FACT-P deterioration (TTFD), defined as time from first Ra-223 treatment to clinical meaningful increase in BPI-SF Worst pain item score and Total FACT-P score, respectively.ResultsThis registry included 300 patients, of whom 105 (35%) were evaluable for FACT-P and BPI-SF during Ra-223 treatment. Forty-five (43%) patients had pain at baseline (PAB) (BPI-SF Worst pain score 5–10 points) and 60 (57%) had no pain at baseline (no-PAB) (BPI-SF Worst pain score 0–4 points). Complete pain response was achieved in 31.4% of the patients, while 58% had an IOCR. The median TTP and TTFD were 5.6 and 5.7 months, respectively, while the difference between PAB and no-PAB patients was not significant.ConclusionsIn contemporary, extensively pretreated mCRPC patients, Ra-223 treatment induced complete pain responses while integrated analysis of HRQoL, pain response, and opioid use demonstrated that the majority of patients derive clinical benefit.

Highlights

Each year, over 1.2 million men are diagnosed with prostate cancer worldwide and approximately 350,000 patients succumb to the consequences of this disease, rendering it the most common noncutaneous cancer in males and the second largest cause of cancerrelated death in men [1]
Baseline characteristics and survival Between April 2015 and March 2018, 305 Metastatic castration-resistant prostate cancer (mCRPC) patients from 20 Dutch hospitals scheduled for Radium-223 dichloride (Ra-223) treatment were included
The percentages of patients experiencing a clinically meaningful improvement of Total Functional Assessment of Cancer Therapy-Prostate (FACT-P) in our cohort was comparable to ALSYMPCA (31.4% and 24.6%, respectively) [5]

Summary

Introduction

Over 1.2 million men are diagnosed with prostate cancer worldwide and approximately 350,000 patients succumb to the consequences of this disease, rendering it the most common noncutaneous cancer in males and the second largest cause of cancerrelated death in men [1]. Contemporary patients treated with Ra-223 are more extensively pretreated with novel agents, like abiraterone, enzalutamide, and cabazitaxel [7] This questions the relevance of HRQoL results from the ALSYMPCA for present mCRPC patients [8]. We assess integrated HRQoL, pain, and opioid use in a contemporary, more extensively pretreated, symptomatic and asymptomatic mCRPC population. A complete or partial pain response (better BPI-SF score and decrease in opioid use) and a better or no change in HRQoL was evaluated as an integrated overall clinical response (IOCR). CONCLUSIONS: In contemporary, extensively pretreated mCRPC patients, Ra-223 treatment induced complete pain responses while integrated analysis of HRQoL, pain response, and opioid use demonstrated that the majority of patients derive clinical benefit

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