Elsevier

European Urology

Volume 67, Issue 3, March 2015, Pages 441-447
European Urology

Platinum Priority – Prostate Cancer
Editorial by Michael R. Harrison and Andrew J. Armstrong on pp. 448–450 of this issue
Outcomes with Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Who Have Poor Performance Status

https://doi.org/10.1016/j.eururo.2014.01.030Get rights and content

Abstract

Background

Although abiraterone acetate (abiraterone) has proven efficacy in two randomised phase 3 trials in metastatic castration-resistant prostate cancer (mCRPC), patients who had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 were either excluded or under-represented in these trials.

Objective

To compare outcomes in ECOG PS 0–1 and ≥2 in mCRPC patients treated with abiraterone.

Design, setting, and participants

Cancer registries from three Canadian centres were used to retrospectively identify mCRPC patients (postdocetaxel and docetaxel-naïve) treated with abiraterone. ECOG PS, clinicopathologic characteristics, prostate-specific antigen (PSA) response, and survival data were collected.

Outcome measurements and statistical analysis

Survival outcomes were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards modelling was used to examine the effect of clinicopathologic characteristics on overall survival (OS) and time to PSA progression.

Results and limitations

A total of 519 patients were identified; 61% (n = 318) and 39% (n = 201) were ECOG PS 0–1 and ≥2, respectively. ECOG PS 0–1 patients were significantly more likely than PS ≥2 patients to achieve a PSA decline ≥50% from baseline (45% vs 32%; p = 0.003, Fisher exact test) and had significantly longer median time to PSA progression (5.2 mo vs 4.1 mo; p = 0.023), median treatment duration (7.4 mo vs 4.5 mo; p < 0.001), and median OS (20.0 mo vs 9.1 mo; p < 0.001). On multivariate analysis, ECOG PS was a significant factor for OS (p < 0.001), time to PSA progression (p = 0.043), and PSA decline (p = 0.002). Potential limitations include the retrospective study design and subjective nature of ECOG PS classification.

Conclusions

ECOG PS ≥2 mCRPC patients treated with abiraterone have inferior outcomes compared with ECOG 0–1 patients, especially in regard to OS. These data indicate that early initiation of abiraterone prior to a decline in PS may be warranted.

Patient summary

We found that advanced prostate cancer patients who have worse performance status (PS) derive less benefit from abiraterone, indicating that earlier treatment before PS declines could improve outcomes.

Introduction

The therapeutic armamentarium for metastatic castration-resistant prostate cancer (mCRPC) has rapidly expanded in recent years [1], [2]. Among the agents now available to treat mCRPC is abiraterone acetate (abiraterone), a novel, orally available inhibitor of CYP17, an enzyme centrally involved in extragonadal androgen synthesis [3]. In phase 3 randomised trials in mCRPC, abiraterone improves radiographic progression-free survival in docetaxel-naïve patients (COU-AA-302 trial) [4] and overall survival (OS) in patients previously treated with docetaxel (COU-AA-301 trial) [5]. The COU-AA-302 trial was restricted to Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–1 patients, while in the COU-AA-301 study, only 10% of enrolled patients were ECOG PS 2. Thus, the activity of abiraterone in ECOG PS ≥2 patients is not well described, which may have important implications for the generalizability of the COU-AA-301 and COU-AA-302 trials, because in clinical practice, abiraterone is commonly used in ECOG PS ≥2 patients [6]. Using an unselected cohort from three large cancer centres in Canada, the aim of this retrospective study was to compare the efficacy of abiraterone in ECOG PS ≥2 and 0–1 patients.

Section snippets

Patient population

Cancer registries at the British Columbia Cancer Agency (BCCA) Alberta Health Services–Cancer Care (AHS-CC) and Princess Margaret Cancer Centre (PM) were reviewed to identify mCRPC patients treated with abiraterone. A total of 519 eligible patients were identified—325 at BCCA, 78 at AHS-CC, and 116 at PM. ECOG PS at initiation of abiraterone was recorded as per assessment of the treating clinician. Patient demographics, prior treatments, and clinicopathologic characteristics were also

Patient population

Baseline clinicopathologic characteristics stratified by ECOG PS are presented in Table 1. The following factors significantly differed between ECOG PS 0–1 and ≥2 patients: median time from commencement of androgen depravation therapy (ADT) to starting abiraterone, serum lactate dehydrogenase (LDH), serum alkaline phosphatase (ALP), and serum albumin. There was also a strong trend towards higher rates of visceral metastases in ECOG PS ≥2 patients, although the difference did not reach

Discussion

In this multicentre, retrospective study, we examined outcomes in ECOG PS 0–1 and ≥2 mCRPC patients treated with abiraterone. Across a cohort of 519 patients, we found that ECOG ≥2 patients had significantly inferior outcomes compared with ECOG 0–1 patients in terms of the proportion of patients who experienced PSA decline ≥50% (45% vs 32%), median time to PSA progression (5.2 mo vs. 4.1 mo) and median OS (20.0 mo vs 9.1 mo). Of note, the survival disadvantage for ECOG PS ≥2 patients in this

Conclusions

Using a large cohort of mCRPC patients across three centres, we examined outcomes with abiraterone in a patient population that has been largely excluded from prior reports, namely, ECOG PS ≥2 patients. Our data indicate that mCRPC patients who have better PS derive greater benefit from abiraterone, highlighting the importance of careful patient selection and optimisation of PS prior to commencing abiraterone.

References (14)

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