Platinum Priority – Prostate CancerEditorial by Michael R. Harrison and Andrew J. Armstrong on pp. 448–450 of this issueOutcomes with Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Who Have Poor Performance Status
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.
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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.
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Cited by (38)
Disease Characteristics and Completion of Treatment in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Radium-223 in an International Early Access Program
2019, Clinical Genitourinary CancerCitation Excerpt :In contrast, patients who for whatever reason died before the fifth injection (ie, those with poor overall survival) would automatically be placed in the 1 to 4 injections group.21 Furthermore, baseline factors identified as being associated with the completion of 5 to 6 radium-223 cycles have been shown to be markers of good prognosis in patients with mCRPC treated with other life-prolonging agents.11,15,22-24 Thus, the finding of prolonged survival in the patients who received 5 to 6 radium-223 injections should be treated with caution because it could be because of the presence of more favorable baseline factors in this patient group.
What kind of patients with castration-naïve prostate cancer can benefit from upfront docetaxel and abiraterone: A systematic review and a network meta-analysis
2018, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :Subgroup analysis performed on the basis of ECOG PS is of 0 vs. 1, because few patients had a score of 2. It was reported that mCRPC patients with ECOG PS ≥ 2 treated with Abi had inferior survival outcomes compared to those with favorable PS [18]. However, patients with ECOG PS ≥ 2 usually had a more aggressive disease phenotype, characterized by increased bone lesions and visceral metastases.
Abiraterone acetate + prednisolone treatment beyond prostate specific antigen and radiographic progression in metastatic castration-resistant prostate cancer patients
2018, Urologic Oncology: Seminars and Original InvestigationsCitation Excerpt :AA and the other new agents have significantly improved the outcomes of men with mCRPC, however, there are a proportion of patients who do not respond to a particular therapy. Some studies investigated the predictive factors for OS in case of AA treatment [9–11]. The aim of this study was to investigate the OS of chemotherapy (CT) refractory mCRPC patients who were treated with AA + P beyond PSA and radiographic progression (PRP) until clinical progression (PRP) in comparison to patients treated only until PRP.