Dataset Information

Efficacy, quality of life, and safety of cabazitaxel in Canadian metastatic castration-resistant prostate cancer patients treated or not with prior abiraterone.

ABSTRACT: INTRODUCTION:In the TROPIC study, cabazitaxel improved overall survival in abiraterone-naïve metastatic castration-resistant prostate cancer (mCRPC) patients post-docetaxel. To evaluate cabazitaxel in routine clinical practice, an international, single-arm trial was conducted. Efficacy, safety, and quality of life (QoL) data were collected from Canadian patients enrolled. Overall survival and progression-free survival were not collected as part of this study. Importantly, prior abiraterone use was obtained and its impact on clinical parameters was examined. METHODS:Sixty-one patients from nine Canadian centres were enrolled, with prior abiraterone use known for 60 patients. Prostate-specific antigen (PSA) response rate, safety, and impact on QoL life were analyzed as a function of prior abiraterone use. RESULTS:Overall, 92% of patients were ECOG 0/1, 88% had bone metastases, and 25% visceral metastases. Patients treated without prior abiraterone (NoPriorAbi) (n=35, 58%) and with prior abiraterone (PriorAbi) (n=25, 42%) had similar baseline characteristics, except for age and prior cumulative docetaxel dose. Median number of cabazitaxel cycles received was similar between groups (NoPriorAbi=6, PriorAbi=7), as was PSA response rate (NoPriorAbi=36.4%, PriorAbi=45.0%, p=0.54). Almost one-third (31%) of patients received prophylactic granulocyte colony-stimulating factors. Most frequent Grade 3/4 toxicities were neutropenia (14.8%); anemia, febrile neutropenia, fatigue (each at 9.8%); and diarrhea (8.2%). No treatment-related adverse event leading to death was observed. QoL and pain were improved with no difference seen between groups. Treatment discontinuation was mainly due to disease progression (45.9%) and adverse events (32.8%). CONCLUSIONS:In routine clinical practice, cabazitaxel's risk-benefit ratio in mCRPC patients previously treated with docetaxel seems to be maintained independent of prior abiraterone use.

SUBMITTER: Saad F

PROVIDER: S-EPMC4839990 | biostudies-literature | 2016 Mar-Apr

REPOSITORIES: biostudies-literature

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Efficacy, quality of life, and safety of cabazitaxel in Canadian metastatic castration-resistant prostate cancer patients treated or not with prior abiraterone.

Saad Fred F Winquist Eric E Hubay Stacey S Berry Scott S Assi Hazem H Levesque Eric E Aucoin Nathalie N Czaykowski Piotr P Lattouf Jean-Baptiste JB Alloul Karine K Stewart John J Sridhar Srikala S SS

Canadian Urological Association journal = Journal de l'Association des urologues du Canada 20160301 3-4

<h4>Introduction</h4>In the TROPIC study, cabazitaxel improved overall survival in abiraterone-naïve metastatic castration-resistant prostate cancer (mCRPC) patients post-docetaxel. To evaluate cabazitaxel in routine clinical practice, an international, single-arm trial was conducted. Efficacy, safety, and quality of life (QoL) data were collected from Canadian patients enrolled. Overall survival and progression-free survival were not collected as part of this study. Importantly, prior abiratero ...[more]

PMID: 27217856

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Project description:PurposeMetastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition.MethodsMAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort.ResultsMedian rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events.ConclusionCombination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.[Media: see text].

Project description:Androgen deprivation therapy remains the single most effective treatment for the initial therapy of advanced prostate cancer, but is uniformly marked by progression to castration-resistant prostate cancer (CRPC). Residual tumor androgens and androgen axis activation are now recognized to play a prominent role in mediating CRPC progression. Despite suppression of circulating testosterone to castrate levels, castration does not eliminate androgens from the prostate tumor microenvironment and residual androgen levels are well within the range capable of activating the androgen receptor (AR) and AR-mediated gene expression. Accordingly, therapeutic strategies that more effectively target production of intratumoral androgens are necessary. The introduction of abiraterone, a potent suppressor of cytochrome P450 17 α-hydroxysteroid dehydrogenase-mediated androgen production, has heralded a new era in the hormonal treatment of men with metastatic CRPC. Herein, the androgen and AR-mediated mechanisms that contribute to CRPC progression and establish cytochrome P450 17 α-hydroxysteroid dehydrogenase as a critical therapeutic target are briefly reviewed. The mechanism of action and pharmacokinetics of abiraterone are reviewed and its recently described activity against AR and 3-β-hydroxysteroid dehydrogenase is discussed. The Phase I and II data initially demonstrating the efficacy of abiraterone and Phase III data supporting its approval for patients with metastatic CRPC are reviewed. The safety and tolerability of abiraterone, including the incidence and management of side effects and potential drug interactions, are discussed. The current place of abiraterone in CRPC therapy is reviewed and early evidence regarding cross-resistance of abiraterone with taxane therapy, mechanisms of resistance to abiraterone, and observations of an abiraterone withdrawal response are presented. Future directions in the use of abiraterone, including optimal dosing strategies, the role of abiraterone in earlier disease settings, including castration sensitive, biochemically recurrent, or localized disease, and the rationale for combinatorial treatment strategies of abiraterone with enzalutamide and other targeted agents are also discussed.

Dataset Information

Efficacy, quality of life, and safety of cabazitaxel in Canadian metastatic castration-resistant prostate cancer patients treated or not with prior abiraterone.

Publications

Efficacy, quality of life, and safety of cabazitaxel in Canadian metastatic castration-resistant prostate cancer patients treated or not with prior abiraterone.

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