A predicitve algorithm for response to abiraterone in metastatic castration relapsed prostate cancer (CRPC).

Abstract

238 Background: Numerous novel therapies for castration relapsed prostate cancer (CRPC) have led to a rapidly evolving approach to its management. Rationalisation of treatment combinations and sequencing of therapy requires identification of men who are more likely to benefit from a particular treatment. An unmet clinical need exists in this domain. We present the findings of a review of patients treated with abiraterone at our centre, and describe a novel predictive algorithm in this setting employing previously undefined pre-determinants of response. Methods: Patients with CRCP treated with abiraterone post-docetaxel at Queen Elizabeth Hospital between August 2010 and February 2012 were identified. Electronic patient records were utilised to extract variables including patient demographics, tumor characteristics, treatment history and other potential predictors of response such as prostate-specific antigen (PSA), hemoglobin (Hb), and alkaline phosphatase (ALP). Outcome measures included overall survival (OS), adverse events and PSA response rate. OS was estimated using the Kaplan-Meier method, and univariate and multivariate analyses were performed on potential prognosticators. Multivariate Beta coefficients were used to generate a predictive algorithm to identify two distinct risk groups. Results: Sixty one patients met the inclusion criteria. From starting abiraterone, the median OS was 12.6m, and median duration of follow-up was 11.5m. In univariate analysis seven factors impacted OS: age, response duration to androgen deprivation therapy (ADT), Hb, time from diagnosis to starting abiraterone, and ALP. Subsequent multivariate analysis identified three independent predictors of OS: duration of response to ADT (HR: 0.95, p=0.006), performance status (HR: 0.71, p=0.013), and baseline Hb (HR: 0.47, p=<0.001). A predictive algorithm dividing the cohort into high- and low-risk groups derived a diverging Kaplan-Meier curve without overlapping 95% CI’s. The low risk group did not reach median survival. Conclusions: This retrospective review has identified a predictive scoring algorithm for response to abiraterone in CRPC. We suggest that further analysis in the form of external validation is needed in order to justify its use in individualisation of patient management and stratification of patients for prospective clinical trials.

Predictors of long-term response to abiraterone in patients with metastastic castration-resistant prostate cancer: a retrospective cohort study

“…In particular, the presence of synchronous metastases at diagnosis and visceral disease were not associated with a less favorable outcome (although only 8.4% of patients had visceral metastases in our cohort). The lack of a significant association between presence of visceral metastases and radiological progression or survival has been observed in other recent retrospective studies in patients treated with AR-targeted therapies [13, 14]. These findings are in keeping with the results of subgroup and exploratory post-hoc analyses of the COU-AA-301 trial and suggest that all subgroups of patients are likely to derive at least some clinical benefit (not excluding the possibility of a long-term benefit) from abiraterone treatment, irrespective of unfavorable baseline clinical characteristics [5, 15].…”

“…Among clinical biomarkers, the duration of previous androgen-deprivation therapy (ADT) response, or time to CRPC, has received much attention as a potential predictor of response to the new AR-targeted therapies. In a retrospective study in 61 mCRPC patients treated with abiraterone post-docetaxel, Ashfar et al identified three independent predictors of OS: hemoglobin levels, ECOG-PS at starting abiraterone, and duration of response to primary androgen-deprivation therapy [13]. Similarly, time to CRPC ≥12 months and ECOG-PS score 0-1 were associated with improved PFS in a cohort of 173 patients treated with enzalutamide, abiraterone or other hormonal therapies at two French cancer centers [14].…”

Consensus statements on the management of metastatic prostate cancer from the Hong Kong Urological Association and Hong Kong Society of Uro‐Oncology

“…Duration of response to primary ADT was identified as a predictor of OS and of sensitivity to AR axis‐targeted drugs in patients with mCRPC . A relatively short time to castration resistance (i.e.…”

“…A poorer performance status was found to be associated with lower treatment responses and reduced OS among patients with mCRPC . The toxicity profile of a treatment option is of particular concern in patients with a poor performance status; however, as clinical trials generally have excluded patients with a poorer performance status (Eastern Cooperative Oncology Group [ECOG] score of 3 or 4) , treatment options cannot merely be based on a performance status. Instead, they should be individualized, depending on other characteristics of a patient.…”

Chemotherapy in the treatment of metastatic prostate cancer: the present state of the problem

“…В исследовании M. Afshar и соавт. изучали факторы прогноза эффективности абиратерона во 2-й линии терапии после доцетаксела в группе, включающей 61 больного КРРПЖ [44]. При мультивариантном анализе выявлены 3 незави-симых фактора прогноза ОВ: длительность ответа на первичную АДТ (р = 0,006), статус общего состоя-ния больного (р = 0,013) и исходный уровень гемогло-бина (р < 0,001).…”