External Validation of a Prognostic Model Predicting Overall Survival in Metastatic Castrate-resistant Prostate Cancer Patients Treated with Abiraterone

Ravi, Praful; Mateo, Joaquín; Lorente, David; Altavilla, Amelia; Ferraldeschi, Roberta; Sideris, Spyridon; Grist, Emily; Smith, Alan D.; Wong, Sophia; Bianchini, Diletta; Attard, Gerhardt

doi:10.1016/j.eururo.2014.03.020

Cited by 23 publications

(19 citation statements)

References 9 publications

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“…These data highlight that a subset of PCs are biologically more responsive to AR pathway manipulations, and will exhibit a superior response to AR targeted therapies such as abirarerone. Additionally, several prior have investigated clinical parameters, including primary ADT duration, associated with PFS and overall survival (OS) in patients with mCRPC treated with abiraterone (9–16). We sought to confirm the impact of baseline clinical characteristics on abiraterone duration and specifically evaluate duration of prior therapies including primary ADT, SHT, and chemotherapy on abiraterone duration.…”

Section: Introductionmentioning

confidence: 99%

Predictors of duration of abiraterone acetate in men with castration-resistant prostate cancer

Werner

Fiorillo

et al. 2016

Prostate Cancer Prostatic Dis

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Background Androgen receptor signaling remains important in castration resistant prostate cancer (CRPC) as demonstrated by the efficacy of abiraterone acetate (henceforth abiraterone) in phase III trials. Given that heterogeneous patient responses are observed, we sought to determine clinical factors associated with duration of abiraterone. Methods We retrospectively identified patients with CRPC treated with abiraterone in our database. Patient characteristics and types and duration of prostate cancer therapies were analyzed. These parameters were analyzed with duration of abiraterone in univariate and multivariable analyses. Results We identified 161 patients who had received abiraterone. All had received primary androgen deprivation therapy (ADT), 86% prior secondary hormone therapy, and 33% prior chemotherapy. The median duration of primary ADT was 23 months, duration of secondary hormone therapy (excluding abiraterone) was 17 months, and duration of chemotherapy was 8 months. We demonstrated that lower prostate specific antigen (PSA) at abiraterone initiation, longer primary ADT duration, no prior ketoconazole, no prior chemotherapy and longer chemotherapy duration were associated with a longer duration on abiraterone in univariate analysis. In multivariable analysis, duration of primary ADT (duration of abiraterone 9 versus 13 months for ≤12 versus >12 months, p=0.03) and no use of prior chemotherapy (duration of abiraterone 16 versus 7 months for no versus yes prior chemotherapy, p<0.01) were associated with duration of abiraterone. Conclusions Several clinical parameters including type and duration of prior therapy are predictive of responsiveness to abiraterone. These parameters are logical and correlate with smaller disease burden or less exposure to prostate cancer therapies. This information can help physicians counsel patients about the potential durability of efficacy of abiraterone. Identifying predictive biomarkers that inform patient selection for therapy is critical to optimizing treatment outcomes.

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Section: Introductionmentioning

confidence: 99%

Predictors of duration of abiraterone acetate in men with castration-resistant prostate cancer

Werner

Fiorillo

et al. 2016

Prostate Cancer Prostatic Dis

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“…These results contrast with those of an external validation of the prognostic index performed by Ravi et al at Royal Marsden. 6 In their cohort of 64 chemotherapy-naïve patients, low albumin was the only independent factor predicting OS in multivariable analysis. However, this was a relatively small validation cohort which included only one chemotherapy-naïve patient with poor prognosis disease, and differed from our cohort in that no chemotherapy-naïve patients with ECOG PS ≥ 2 were included whereas these patients comprised 38% of our cohort.…”

Section: Cuaj -Original Research Khalaf Et Al Stratifying Clinical Oumentioning

confidence: 99%

“…5 The utility of this model in chemotherapy-naïve patients has also been examined in a preliminary analysis incorporating only 64 patients. 6 The COU-302 trial which evaluated abiraterone in chemotherapy-naïve patients with CRPC showed a significantly longer OS than the post-chemotherapy COU-301 trial (34.7 vs 15.8 months), 3,7 and the performance of our 6-factor prognostic model in that setting is currently unknown. The aim of our study was to determine whether this prognostic model determines clinically relevant prognostic groups in chemotherapy-naïve patients treated with abiraterone in a real-world setting across six cancer centres in British Columbia, Canada.…”

Section: Introductionmentioning

confidence: 99%

A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

Khalaf

Avilés²,

Azad³

et al. 2017

CUAJ

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Introduction: Recently, a prognostic index including six risk factors (RFs) (unfavourable ECOG performance status [PS], presence of liver metastases, short response to luteinizing hormonereleasing hormone [LHRH] agonists/antagonists, low albumin, increased alkaline phosphatase [ALP] and lactate dehydrogenase [LDH]) was developed from the COU-AA-301 trial in postchemotherapy metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate. Our primary objective was to evaluate this model in a cohort of chemotherapy-naive mCRPC patients receiving abiraterone. Methods: We identified 197 chemotherapy-naive patients who received abiraterone at six BC Cancer Agency centres and who had complete information on all six RFs. Study endpoints were prostate-specific antigen (PSA) response rate (RR), time to PSA progression, time on treatment, and overall survival (OS). PSA RR and survival outcomes were compared using Χ 2 test and log-

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“…Model subsequently validated using data from population-based settings. 45 Factors identified also shown to be predictive of response to abiraterone, 46,47 along with bone and lymph node metastases and high neutrophil/lymphocyte ratio. 47 Model may also have application in the prechemotherapy setting.…”

Section: Not Applicablementioning

confidence: 93%

“…47 Model may also have application in the prechemotherapy setting. 45 Subsequent analysis suggests that baseline serum androgen levels are prognostic for OS. 27 Chi KN, et al 48 …”

Section: Not Applicablementioning

confidence: 98%

Treating Patients with Metastatic Castration Resistant Prostate Cancer: A Comprehensive Review of Available Therapies

et al. 2015

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New therapies for metastatic castration resistant prostate cancer have brought new challenges with regard to treatment selection and sequencing. While hormonal agents provide good therapeutic responses, resistance may be intrinsic without prior drug exposure. Identifying predictors of response and relevant biomarkers will allow therapies to be more precisely tailored to individual patient profiles.

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External Validation of a Prognostic Model Predicting Overall Survival in Metastatic Castrate-resistant Prostate Cancer Patients Treated with Abiraterone

Cited by 23 publications

References 9 publications

Predictors of duration of abiraterone acetate in men with castration-resistant prostate cancer

Predictors of duration of abiraterone acetate in men with castration-resistant prostate cancer

A prognostic model for stratifying clinical outcomes in chemotherapy-naive metastatic castration-resistant prostate cancer patients treated with abiraterone acetate

Treating Patients with Metastatic Castration Resistant Prostate Cancer: A Comprehensive Review of Available Therapies

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