Oncology

Prostate Cancer

ALSYMPCA: Quality-of-Life Scores Predict Overall Survival

patient care perspectives by Oliver Sartor, MD

Overview

For the patient with metastatic castration-resistant prostate cancer (mCRPC), the kinetics of disease progression can be subtle. The natural history of mCRPC often includes worsening symptomatology and a progressive decline in health-related quality of life (HRQoL) and bone pain. Accordingly, HRQoL is recognized increasingly as an important outcome of any treatment modality. HRQoL is considered a multidomain phenomenon that captures an individual’s perceived mental, emotional, physical, and social well-being over time. The multidimensional Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire is a commonly used disease-specific instrument for assessing HRQoL in patients with prostate cancer. Pain, fatigue, and physical function are major contributors to HRQoL in mCRPC.

Radium-223 dichloride (²²³RaCl2) was shown in the phase 3 ALSYMPCA (Alpharadin in Symptomatic Prostate Cancer) study to improve overall survival (OS), with meaningful improvements vs placebo in HRQoL. In a subsequent analysis of ALSYMPCA, HRQoL at baseline and changes in HRQoL were determined to be prognostic of OS in mCRPC.

Oliver Sartor, MD

C. E. and Bernadine Laborde Professor of Cancer Research
Medical Director, Tulane Cancer Center
Associate Dean for Oncology
Tulane University School of Medicine
New Orleans, LA

In abstract 177 from the 2017 American Society of Clinical Oncology Genitourinary Cancers Symposia, Nilsson et al reported on the relationship between HRQoL and OS in mCRPC patients treated in the phase 3 radium trial, ALSYMPCA. In this particular trial, HRQoL was assessed by a FACT-P questionnaire at baseline, Week 16, Week 24, and follow-up. Several parameters of note were reported in this presentation.

First, both baseline FACT-P total scores and improvements and FACT-P total scores were related to OS.
Second, the physical well-being subscale, emotional well-being subscale, functional well-being subscale, and prostate cancer score subscale all demonstrated similar relationships, whereas the social subscale did not.

In further analysis, every 10-point increase (ie, improvement) in FACT-P total score was associated with a 7% reduction in the risk of death.

These data clearly indicate that simple patient-reported FACT-P scores can have prognostic importance, at baseline as well as for serially monitored patients, with regard to key endpoints such as OS.

“In further analysis, every 10-point increase (ie, improvement) in FACT-P total score was associated with a 7% reduction in the risk of death.”

Oliver Sartor, MD

Few studies have been reported in this domain in prostate cancer, and it is important to recognize that these types of HRQoL indicators can have significant predictive impact on patients with advanced disease.

The way that clinicians are thinking today, they’re typically using one of the hormones pretty early, either abiraterone or enzalutamide. There are prospective trials comparing abiraterone +/- radium-223 and enzalutamide +/- radium-223, but we don’t have those results yet. So, clearly there’s so much to learn, and it’s now quite intriguing with these biomarkers coming out. Crucial questions need to be answered, such as: which of these patients are progressing because the androgen receptor (AR) is the primary driver, and which are progressing because of non-AR mechanisms? We’re going to figure it out pretty soon as these newer therapies all begin to blossom.

References

Nilsson S, Sartor AO, Vogelzang NJ, et al. Relationship between quality of life and overall survival in metastatic castration-resistant prostate cancer (mCRPC) patients in ALSYMPCA. J Clin Oncol. 2017;35(suppl 6S):Abstract 177.

Sartor O, Coleman RE, Nilsson S, et al. An exploratory analysis of alkaline phosphatase, lactate dehydrogenase, and prostate-specific antigen dynamics in the phase 3 ALSYMPCA trial with radium-223. Ann Oncol. 2017;28(5):1090-1097.

Nussbaum N, George DJ, Abernethy AP, et al. Patient experience in the treatment of metastatic castration-resistant prostate cancer: state of the science. Prostate Cancer Prostatic Dis. 2016;19(2):111-121.