Cabazitaxel for the treatment of castration-resistant prostate cancer

Treatment with docetaxel-based chemotherapy results in improved survival in patients with metastatic castration-resistant prostate cancer. However, all patients eventually develop progressive disease associated with poor outcomes. In this article, we discuss the available second-line therapeutic options following docetaxel, with a special focus on cabazitaxel, which is the first agent to yield extended survival as second-line therapy following docetaxel. Cabazitaxel, a novel semi-synthetic taxane, is effective even in docetaxel-resistant model systems. Recently, results of the Phase III TROPIC trial demonstrated improved survival with cabazitaxel plus prednisone compared with mitoxantrone and prednisone in patients with progressive metastatic castration-resistant prostate cancer, following prior docetaxel, which led to approval by the US FDA.     

Novel therapeutic strategies for metastatic prostate cancer in the post-docetaxel setting

Prostate cancer is the most common noncutaneous cancer and the second leading cause of death from cancer in men in most western countries. Advanced prostate cancer is typically sensitive to androgen‐deprivation therapy, but invariably progresses to the castration‐resistant state. Most current prostate cancer treatments are based on cytotoxicity directed against tumor cells via androgen‐deprivation therapy or chemotherapy. Chemotherapy with docetaxel represents the standard first‐line treatment in patients with castration‐resistant prostate cancer (CRPC). Following progression after treatment with docetaxel, cabazitaxel (XRP6258)–prednisone treatment leads to a significantly longer overall survival (OS) time than with mitoxantrone–prednisone. Several other novel agents are currently being evaluated, including sipuleucel‐T, abiraterone acetate, and MDV3100, as well as the radionuclide alpharadin. The cell‐based immunotherapy sipuleucel‐T produces longer OS times in chemotherapy‐naïve patients, whereas the androgen biosynthesis inhibitor abiraterone acetate results in longer OS times following docetaxel. It is envisioned that these agents will change the standard of care for patients with metastatic CRPC. This review focuses on the clinical development of cabazitaxel and abiraterone acetate.     

SEOM clinical guidelines for the treatment of metastatic prostate cancer (2017)

Androgen deprivation treatment was the only treatment available for metastatic prostate cancer until recently, with docetaxel as the only treatment with a proven survival benefit in castration-resistant prostate cancer (CRPC). Several drugs have been approved in the castration-resistant disease (sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, radium-223). More recently, docetaxel and abiraterone have been moved to the hormone-sensitive disease setting, achieving better patient survival. The purpose of this article is to define the state of the art in the treatment of prostate carcinoma.     

Metastatic castration-resistant prostate cancer (CRPC): preclinical and clinical evidence for the sequential use of novel therapeutics

With five novel therapies shown to improve survival in metastatic castration-resistant prostate cancer (CRPC) in the last 3 years, patients are now living longer and experiencing better quality of life. Since docetaxel became standard of care for men with symptomatic metastatic CRPC, three artificial treatment “spaces” have emerged for prostate cancer drug development: pre-docetaxel, docetaxel combinations, and following docetaxel. Multiple therapies are currently under development in both early and late stage CRPC. Additionally, the novel agents abiraterone, radium-223, cabazitaxel, and enzalutamide have all been approved in the post-docetaxel setting. Strategies for patient selection and treatment sequencing are therefore urgently required. In this comprehensive review, we will summarize the preclinical and clinical data available with regards to sequencing of the novel treatments for CRPC.     

Cabazitaxel in metastatic castration-resistant prostate cancer

Metastatic castration-resistant prostate cancer (CRPC) has a poor prognosis and remains a significant therapeutic challenge. Prior to 2010, docetaxel chemotherapy was the only treatment shown to improve overall survival, symptom control and quality of life in patients with CRPC. Research efforts focused on overcoming chemoresistance to taxanes eventually led to the development of multiple novel anti-tumor agents, including cabazitaxel. Cabazitaxel has recently been shown to significantly improve overall survival compared with mitoxantrone in a large multicenter Phase III study. This article details the preclinical and clinical development of cabazitaxel and discusses the importance of this novel chemotherapy in CRPC. The authors also discuss the challenges now facing the future use of cabazitaxel in CRPC, including the determination of the optimal dose of cabazitaxel in patients with advanced CRPC, the ideal sequencing of cabazitaxel relative to other anti-tumor treatments, appropriate patient selection and novel strategies for the assessment of treatment response.     

Evolving therapeutic paradigms for advanced prostate cancer

Improving survival in metastatic castration-resistant prostate cancer (CRPC) is no longer an elusive goal. With the expansion of knowledge regarding the biology of the disease, we are witnessing a plethora of novel therapeutics that are undergoing testing in clinical trials. Since the approval of docetaxel for metastatic CRPC in 2004, three additional agents have demonstrated improvements in overall survival in randomized phase III trials: two agents (cabazitaxel and sipuleucel-T) were approved by the FDA in 2010, and a third (abiraterone) was approved in April of 2011. A threshold has clearly been crossed in the management of advanced prostate cancer; however, the impact on survival has been relatively modest, and efforts at personalized therapy have lagged behind those for other solid tumors. Further meaningful advances are needed, and the foundation for future clinical trials must be high-quality, high-impact translational science that focuses on disease biology, the defining of relevant pathways and validated predictive biomarkers, and adequate preclinical characterization of agents and combinations that will facilitate more personalized therapy.     

New treatment options for patients with metastatic castration-resistant prostate cancer

Chemotherapy for men with metastatic castration-resistant prostate cancer (CRPC) conferred no survival advantage until 2004 when docetaxel was shown to improve survival when compared with mitoxantrone, which was approved for palliation of symptomatic disease in 1996. Since then, clinical trials have concentrated on three main populations of patients with metastatic CRPC: those who are chemotherapy naïve and are asymptomatic or minimally symptomatic, those who need docetaxel therapy, and those who have received docetaxel previously and/or those with symptomatic disease. Over the last year, four Phase III therapeutic trials have met their primary endpoint of improved overall survival: sipuleucel-T in the pre-chemotherapy setting, cabazitaxel and abiraterone in the post-docetaxel setting, and radium-223 for those with symptomatic bone metastases who have received or are not suitable to receive docetaxel. In addition to these therapeutic trials, a Phase III head-to-head trial of denosumab compared to zoledronic acid showed that denosumab was superior to zoledronic acid in delaying or preventing skeletal related events. As a result, the treatment paradigm for metastatic CRPC is changing rapidly. This paper reviews the data from these five completed Phase III trials and places these new agents, as well as those in ongoing Phase III trials, in the context of the old treatment paradigm for metastatic CRPC and discusses some of the challenges ahead for determining optimal timing and sequencing of treatments for metastatic CRPC.     

Medical strategies for treatment of castration resistant prostate cancer (CRPC) docetaxel resistant

Current landscape of treatment of castration-resistant prostate cancer (CRPC) has recently changed. Cabazitaxel, a new taxane with potential antineoplastic activity, has been approved by Food and Drug Administration (FDA) after docetaxel failure. In a phase III trial, cabazitaxel showed increased overall survival (OS) compared with mitoxantrone (15.1 vs. 12.7 mo, HR 0.70, 95% CI 0.59-0.83, p < 0.0001). Furthermore, chemotherapy is not the only strategy available: several studies have shown as CRPC remains dependent on androgen receptor function for growth. Abiraterone acetate, an irreversible inhibitor of CYP17, has also been approved by FDA after docetaxel failure. In a phase III trial comparing abiraterone acetate to placebo, abiraterone showed improvement in OS (14.8 vs. 10.4 mo, HR 0.65, 95% CI 0.54-0.77; p < 0.0001). This review will discuss current options and the ongoing trials for second-line treatment of CRPC including chemotherapy, hormonal therapies, antiangiogenetic and immune strategies.     

Pleuropulmonary and Lymph Node Progression after Docetaxel – Benefits from Treatment with Cabazitaxel in Metastatic Prostate Cancer

Introduction

To date, there are no guidelines for a rational and more favourable sequence of treatment after docetaxel. Two drugs (cabazitaxel and abiraterone) have recently been approved as second-line treatment after docetaxel failure in metastatic castration-resistant prostate cancer (mCRPC), but there are no studies comparing abiraterone versus cabazitaxel. The most suitable drug is chosen based on the physician''s opinion and the patient''s characteristics. In patients with a good performance status who are able to receive either treatment, it would be convenient to begin with cabazitaxel and to reserve abiraterone in case there is a worsening of the general status, in consideration of abiraterone''s more favourable toxicity profile.

Case Report

We describe the case of a 74-year-old male with mCRPC who presented with an interesting and uncommon tumour dissemination (pleuropulmonary) occurring after the first standard treatment with docetaxel. Intravenous treatment with cabazitaxel 25 mg/m² and oral prednisone 10 mg continuously was initiated. The patient received a total of 8 cycles of chemotherapy. A reduction of mediastinal adenopathies and infrarenal para-aortic stable bone involvement and an absence of pleural effusion were observed. No relevant toxicity was noted. Since February 2012, a progressive PSA increase without clinical deterioration has been noted.

Conclusions

The selection criteria for second- and third-line systemic treatment and the excellent response obtained with cabazitaxel in an unusual disease setting are described. The results confirm the long duration and quality of response of cabazitaxel treatment. Further therapeutic options in this group of patients are suggested.Key words: Cabazitaxel, Castration-resistant prostate cancer, Pleuropulmonary progression     

Cabazitaxel après docétaxel,une nouvelle option dans le cancer métastatique de la prostate résistant à la castration

The management of patients with metastatic castration-resistant prostate cancer is a real challenge. Indeed, after a first line chemotherapy with docetaxel, there was no standard because the treatments were ineffective. Today, several therapeutic options are available with the development of new therapies. Among them, cabazitaxel, semi-synthetic derivative of a natural taxoid, has been developed to its low recognition by the MDR system and power distribution including brain. This new chemotherapy was assessed in patients with metastatic castration-resistant prostate cancer whose disease has progressed during or after docetaxel-based therapy. Treatment with cabazitaxel plus prednisone has improved overall survival of 2.4 months compared to mitoxantrone in the TROPIC phase III. However, hematologic toxicity may be limiting with a risk of febrile neutropenia; hematopoietic growth factors are advised in case of significant neutropenia. The cabazitaxel, Jevtana^®, has been approved in second line after docetaxel. Its position in relation to new types of hormone therapy, as abiraterone acetate, in the same indication requires further investigations, including predictive factors of response. Studies are on going in first line indication (compared to docetaxel) and associated to other new hormone therapies.     

Second-Line Cabazitaxel Treatment in Castration-Resistant Prostate Cancer Clinical Trials Compared to Standard of Care in CAPRI: Observational Study in the Netherlands

BackgroundCabazitaxel has been shown to improve overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients after docetaxel in the TROPIC trial. However, trial populations may not reflect the real-world population. We compared patient characteristics and outcomes of cabazitaxel within and outside trials (standard of care, SOC).Patients and MethodsmCRPC patients treated with cabazitaxel directly after docetaxel therapy before 2017 were retrospectively identified and followed to 2018. Patients were grouped on the basis of treatment within a trial or SOC. Outcomes included OS and prostate-specific antigen (PSA) response.ResultsFrom 3616 patients in the CAPRI registry, we identified 356 patients treated with cabazitaxel, with 173 patients treated in the second line. Trial patients had favorable prognostic factors: fewer symptoms, less visceral disease, lower lactate dehydrogenase, higher hemoglobin, more docetaxel cycles, and longer treatment-free interval since docetaxel therapy. PSA response (≥ 50% decline) was 28 versus 12%, respectively (P = .209). Median OS was 13.6 versus 9.6 months for trial and SOC subgroups, respectively (hazard ratio = 0.73, P = .067). After correction for prognostic factors, there was no difference in survival (hazard ratio = 1.00, P = .999). Longer duration of androgen deprivation therapy treatment, lower lactate dehydrogenase, and lower PSA were associated with longer OS; visceral disease had a trend for shorter OS.ConclusionPatients treated with cabazitaxel in trials were fitter and showed outcomes comparable to registration trials. Conversely, those treated in daily practice showed features of more aggressive disease and worse outcome. This underlines the importance of adequate estimation of trial eligibility and health status of mCRPC patients in daily practice to ensure optimal outcomes.     

βIII-tubulin enhances efficacy of cabazitaxel as compared with docetaxel

Cabazitaxel is a novel taxane approved for treatment of metastatic hormone-refractory prostate cancer in patients pretreated with docetaxel. Cabazitaxel, docetaxel, and paclitaxel bind specifically to tubulin in microtubules, disrupting functions essential to tumor growth. High levels of βIII-tubulin isotype expression are associated with tumor aggressivity and drug resistance. To understand cabazitaxel’s increased efficacy, we examined binding of radio-labeled cabazitaxel and docetaxel to microtubules and the drugs’ suppression of microtubule dynamic instability in vitro in microtubules assembled from purified bovine brain tubulin containing or devoid of βIII-tubulin. We found that cabazitaxel suppresses microtubule dynamic instability significantly more potently in the presence of βIII-tubulin than in its absence. In contrast, docetaxel showed no βIII-tubulin-enhanced microtubule stabilization. We also asked if the selective potency of cabazitaxel on βIII-tubulin-containing purified microtubules in vitro extends to cabazitaxel’s effects in human tumor cells. Using MCF7 human breast adenocarcinoma cells, we found that cabazitaxel also suppressed microtubule shortening rates, shortening lengths, and dynamicity significantly more strongly in cells with normal levels of βIII-tubulin than after 50% reduction of βIII-tubulin expression by siRNA knockdown. Cabazitaxel also more strongly induced mitotic arrest in MCF7 cells with normal βIII-tubulin levels than after βIII-tubulin reduction. In contrast, docetaxel had little or no βIII-tubulin-dependent selective effect on microtubule dynamics or mitotic arrest. The selective potency of cabazitaxel on purified βIII-tubulin-containing microtubules and in cells expressing βIII-tubulin suggests that cabazitaxel may be unusual among microtubule-targeted drugs in its superior anti-tumor efficacy in tumors overexpressing βIII-tubulin.

     

Current and emerging treatments in the management of castration-resistant prostate cancer

Historically, patients diagnosed with castration-resistant prostate cancer (CRPC) have had poor survival rates. In recent years there have been significant advances in the treatment of CRPC. In addition to cytotoxic chemotherapy, treating physicians and their patients now have the option of several new agents that target not only androgen- and cytotoxic-mediated pathways, but also the patient's own immune system. In this review, we discuss the existing US FDA-approved therapies, a wide range of experimental treatments that are currently in development, and also palliative options for patients with symptoms secondary to metastatic disease. We also discuss the progression-free survival, overall survival, PSA levels and other end points used in clinical trials in order to evaluate and compare novel therapeutic options for CRPC. Currently, docetaxel and sipuleucel-T are the first line treatment options for patients with CRPC; approved second-line treatments for first line treatment failure are limited to cabazitaxel and abiraterone acetate. Recently, a few experimental agents, MDV3100 and radium-223, have demonstrated efficacy in improving overall survival in patients who had previously failed chemotherapy. These agents, and possibly others introduced in this review, are positioned to change the treatment landscape for CRPC.     

Current and emerging treatments in the management of castration-resistant prostate cancer

Historically, patients diagnosed with castration-resistant prostate cancer (CRPC) have had poor survival rates. In recent years there have been significant advances in the treatment of CRPC. In addition to cytotoxic chemotherapy, treating physicians and their patients now have the option of several new agents that target not only androgen- and cytotoxic-mediated pathways, but also the patient’s own immune system. In this review, we discuss the existing US FDA-approved therapies, a wide range of experimental treatments that are currently in development, and also palliative options for patients with symptoms secondary to metastatic disease. We also discuss the progression-free survival, overall survival, PSA levels and other end points used in clinical trials in order to evaluate and compare novel therapeutic options for CRPC. Currently, docetaxel and sipuleucel-T are the first line treatment options for patients with CRPC; approved second-line treatments for first line treatment failure are limited to cabazitaxel and abiraterone acetate. Recently, a few experimental agents, MDV3100 and radium-223, have demonstrated efficacy in improving overall survival in patients who had previously failed chemotherapy. These agents, and possibly others introduced in this review, are positioned to change the treatment landscape for CRPC.     

Acétate d’abiratérone (AA) : comment prescrire l’abiratérone et à qui en 2014 ?

Abiraterone acetate (AA) is a selective inhibitor of cytochrom p450 (CYP)17 which is required for androgen biosynthesis, and can block the androgens synthesis by testicles, surrenals and intratumoral secretion. In phase I and II studies in patients with prostate cancer, therapy with AA 250-2000 mg once daily demonstrated reductions in prostate specific antigen (PSA), and/or circulating tumor cells (CTCs). In two large phase III trials in patients with metastatic castration resistant prostate cancer (CRPC) in post-docetaxel and pre-docetaxel setting, AA plus prednisone compared with placebo plus prednisone demonstrated a significant superior overall survival in post-docetaxel setting, and a superior radiological PFS in pre-docetaxel setting. Based of these results, AA is approved in metastatic CRPC patients in post-docetaxel setting or pre-docetaxel setting in 2013.     

Prognostic significance of grade 3/4 neutropenia in Japanese prostate cancer patients treated with cabazitaxel

The present study aimed to evaluate the efficacy of cabazitaxel in Japanese patients affected by metastatic castration‐resistant prostate cancer (mCRPC) previously treated with a docetaxel‐containing regimen. In this retrospective study, 41 patients with mCRPC treated with cabazitaxel at Keio University Hospital were retrospectively reviewed. Cabazitaxel at a dose of 20‐25 mg/m² was administered every 3 or 4 weeks. Clinicopathological factors and laboratory data were collected to assess the prognostic factors for overall survival (OS) and progression‐free survival (PFS). An upfront dose‐reduction was required in 52.5% of patients due to their reduced general condition or advanced age. Prophylactic G‐CSF was prescribed to all the patients. Grade ≥3 neutropenia and febrile neutropenia occurred in 21 patients (53.6%) and 3 patients (6.8%), respectively. Treatment was generally well tolerated, with a median of 5 cycles (range 1‐17). Median PFS and OS from the start of cabazitaxel treatment were 4.4 and 15.0 months (95% CI 8.9‐21.2), respectively. Waterfall plot analysis revealed that a prostate‐specific antigen (PSA) decline >50% was noticed in n = 11 patients receiving cabazitaxel (26.8%). Univariate analysis revealed that poor performance status, PSA ≥100 ng/mL prior to cabazitaxel treatment, visceral metastasis, absence of grade 3/4 neutropenia during cabazitaxel therapy and neutrophil‐lymphocyte ratio were significantly associated with shorter overall survival. Multivariate analysis revealed that poor performance status, visceral metastasis, and the absence of grade 3/4 neutropenia during cabazitaxel therapy were the independent prognostic indicators for OS. The practical implication of our results might be to tailor cabazitaxel dosing on the basis of its hematological effects.     

Broadening horizons in medical management of prostate cancer

HORMONAL THERAPY: Testosterone suppression achieved either medically or surgically is the standard initial treatment for men with advanced prostate cancer. Most men respond but the disease progresses after a median of 1-2 years. Clinical trials suggest that intermittent androgen deprivation therapy (ADT) provides equal or longer time to castration-independence than continuous ADT, and is preferred, especially since there are subtle long-term toxicities associated with ADT. Further hormonal manipulations (including addition and withdrawal of peripheral antiandrogens, steroid synthesis inhibitors such as ketoconazole, and estrogens) can be transiently effective in selected patients with castration-resistant prostate cancer (CRPC). Androgen-dependent signalling pathways remain active in most men with CRPC and are associated with mutation, changes in expression or modulation of the androgen receptor (AR); abiraterone acetate and MDV3100 are promising drugs being evaluated in clinical trials that may lead to further hormonal response. CHEMOTHERAPY: Eventually men who progress rapidly, are symptomatic, and/or develop metastasis to visceral organs require chemotherapy. Three-weekly docetaxel with prednisone has been shown to improve survival and relieve symptoms but eventually men develop progressive disease or become intolerant to docetaxel. Multiple trials are evaluating new drugs (mainly molecular targeted agents) either given first line with docetaxel chemotherapy, or to men who have progressive disease after receiving docetaxel. Cabazitaxel was shown recently to improve survival as compared to mitoxantrone when used second line and has been approved by the United States Food and Drug Administration (FDA). CONCLUSION: Despite major advances, treatment of men with advanced CRPC remains a challenge both for the seeker and giver of care.     

Metronomic Oral Cyclophosphamide Chemotherapy Possibly Contributes to Stabilization of Disease in Patients With Metastatic Castration-Resistant Prostate Cancer: A Prospective Analysis of Consecutive Cases

Introduction/BackgroundCastration-resistant prostate cancer remains a therapeutic challenge, even after establishing the survival benefits of docetaxel chemotherapy. Metronomic chemotherapy stabilizes various cancers through antiangiogenic and immunomodulatory effects. We evaluate the activity of metronomic oral cyclophosphamide chemotherapy in metastatic CRPC patients, and assess predictive factors for clinical outcomes.Patients and MethodsTwenty-four patients with metastatic CRPC received an oral cyclophosphamide and dexamethasone regimen. Of those, 11 patients (45.8%) had been exposed and resistant to previous docetaxel chemotherapy. Six patients had refused to receive docetaxel chemotherapy, and 7 patients could not receive the therapy because of deteriorated performance status. All patients had already shown resistance to continuous dexamethasone therapy. Demographic and clinical data were collected prospectively.ResultsA total of 16 patients (66.7%) experienced a reduction in PSA levels, and PSA decrease ≥ 50% was observed in 8 patients (33.3%). The median PSA progression-free and overall survival were 5.0 months and 19.0 months, respectively. The favorable PSA decrease had no associations with the progression-free and overall survival, but 7 patients (29.2%) in whom response had exceeded 8 months achieved long overall survival of 28 months in median. None of the patients discontinued therapy because of the presence of toxicities.ConclusionMetronomic cyclophosphamide is an active and well tolerated chemotherapy and can be an option for metastatic CRPC patients. The benefit of this regimen could not always be evaluated according to a favorable PSA decrease; thus, we must identify the predictive factors of response other than known clinical factors.     

沙利度胺联合化疗治疗骨转移去势抵抗性前列腺癌的疗效观察

背景与目的:多西他赛联合泼尼松治疗可延长转移性去势抵抗性前列腺癌患者的生存期,血管生成抑制剂也可抑制肿瘤生长,联合治疗的疗效目前仍不明确.该研究旨在观察沙利度胺联合多西他赛和泼尼松治疗骨转移的去势抵抗性前列腺癌的近期临床疗效.方法:收集2008年12月—2015年6月南京军区福州总医院收治的骨转移去势抵抗性前列腺癌患者78例,其中40例作为对照组给予多西他赛和泼尼松方案化疗,38例作为观察组在对照组的基础上给予沙利度胺联合化疗,观察两组有效率、骨痛缓解率、前列腺特异性抗原(prostate specific antigen,PSA)无进展时间、无疾病进展时间及总生存时间,并评价不良反应.结果:观察组有效率为65.79%,PSA无进展时间为4.13个月,无疾病进展时间为4.25个月,骨痛缓解率为86.84%;对照组有效率为40.00%,PSA无进展时间为3.54个月,无疾病进展时间为3.75个月,骨痛缓解率为60.00%,观察组均高于对照组,差异有统计学意义(P<0.05).治疗后两组总生存时间、患者恶心呕吐及白细胞下降等不良反应发生率比较,差异无统计学意义(P>0.05).结论:沙利度胺联合化疗治疗骨转移的去势抵抗性前列腺癌近期临床效果满意,安全,不增加不良反应,具有较高的临床应用价值.     

No significant impact of prior treatment profile with docetaxel on the efficacy of cabazitaxel in Japanese patients with metastatic castration-resistant prostate cancer

The objective of this study was to retrospectively analyze the oncological outcomes of Japanese patients with metastatic castration-resistant prostate cancer (mCRPC) who received cabazitaxel. This study included a total of 63 consecutive Japanese mCRPC patients treated with cabazitaxel following the failure of docetaxel, and assessed the prognostic significance of cabazitaxel therapy in these patients focusing on the association of efficacies between two taxane agents. After treatment with cabazitaxel (median 5 cycles), prostate-specific antigen (PSA) decline was observed in 39 patients (61.9%), including 13 (27.0%) achieving the response defined by PSA decline ≥50%. The median progression-free survival (PFS) and overall survival (OS) periods after the introduction of cabazitaxel were 4.1 and 14.8 months, respectively. The response rate to cabazitaxel was not significantly different between responders and non-responders to prior docetaxel, and there was no significant correlation between the PFSs with docetaxel and cabazitaxel. Furthermore, univariate analyses of several parameters identified the performance status (PS) and clinical symptoms, but not the cycles of docetaxel therapy, total amount of administered docetaxel or objective response to docetaxel therapy, as significant predictors of OS on cabazitaxel therapy, of which only PS was independently associated with OS on multivariate analysis. These findings suggest that oncological outcomes in Japanese mCRPC patients receiving cabazitaxel are generally satisfactory, irrespective of the profiles related to prior treatment with docetaxel, and that it might be preferable to introduce cabazitaxel to mCRPC patients with a good PS to maximize the prognostic benefit of this agent.