Efficacy Of Cabazitaxel Research Articles

Abstract 2567: Cabazitaxel chemotherapy targets mitotic kinesins resulting in multi-nucleation of prostate cancer cells: A novel mechanism of cross-resistance with antiandrogens in advanced CRPC

Abstract Progression to castration-resistant prostate cancer (CRPC) is characterized by increased androgen receptor (AR) and activated AR signaling despite castrate levels of androgens. The FDA-approved next generation microtubule stabilizing taxane, Cabazitaxel (CBZ) and novel anti-androgen Enzalutamide (MDV) have demonstrated additional survival benefits for patients with advanced CRPC. The present study pursued the mechanism of therapeutic resistance to CBZ and antiandrogen treatment in models of CRPC. The effect CBZ and/or MDV was examined in human prostate cancer cells: androgen independent (DU145 and PC3), androgen responsive (LNCaP and VCaP) and CRPC (22Rv1 and PC3-ARv567, harboring AR variants). Cell viability assessment revealed that CRPC PC3-ARv567es and the androgen-sensitive VCaP cells exhibited resistance to CBZ; however the 22Rv1 cells responded to CBZ and MDV combination with a significant increase in growth (P<0.05). Confocal microscopy and Western blot analysis were used to establish the subcellular localization and protein expression in prostate cancer cells. Antiandrogen (MDV) treatment (24hrs;1uM) led to a cytoplasmic accumulation of AR, while treatment with CBZ (72hrs, 35 -100nM) decreased AR expression, but it did not inhibit its nuclear localization. Furthermore CBZ induced mono-astral spindle formation, centrosomal clustering and multi-nucleation, potentially via targeting the “pro-mitotic kinesins”, MCAK and HSET, regardless of androgen status. To determine the in vivo efficacy of CBZ and androgen axis targeting, we used a transgenic mouse model of prostate cancer (Dominant negative TGFβRII/TRAMP) that is driven to metastasis by epithelial-mesenchymal transition (EMT). Immunohistochemical profiling of prostate tumors from untreated control and CBZ treated mice demonstrated that combination of CBZ and castration-induced androgen depletion reduced kinesin and AR expression and reversed EMT, impairing prostate cancer progression. Furthermore, CBZ treatment restored normal glandular differentiation (by H&E), without significant effect on apoptosis in tumor epithelial cells. Cell proliferation was significantly decreased in response to castration-induced androgen depletion in combination with CBZ (2wks) (P<0.05). These findings support the ability of CBZ to target pro-mitotic kinesins, providing an insight into a new mechanism of action of this taxane that can be exploited for targeting CRPC patients with kinesin overexpression. Moreover, the in vivo evidence identified that CBZ chemotherapy has novel effects beyond suppressing tumor growth, by inducing prostate glandular differentiation. This study is of translational significance in introducing a novel mechanism to overcome cross-resistance to CBZ chemotherapy and anti-androgens in advanced CRPC. Citation Format: Sarah K. Martin, Hong Pu, Craig Horbinski, Zheng Cao, Natasha Kyprianou. Cabazitaxel chemotherapy targets mitotic kinesins resulting in multi-nucleation of prostate cancer cells: A novel mechanism of cross-resistance with antiandrogens in advanced CRPC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2567. doi:10.1158/1538-7445.AM2015-2567

Efficacy of Cabazitaxel in Castration-resistant Prostate Cancer Is Independent of the Presence of AR-V7 in Circulating Tumor Cells

BackgroundAndrogen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs) from patients with metastatic castration-resistant prostate cancer (mCRPC) was recently demonstrated to be associated with resistance to abiraterone and enzalutamide. Cabazitaxel might, however, remain effective in AR-V7-positive patients. ObjectiveTo investigate the association between AR-V7 expression in CTCs and resistance to cabazitaxel. Design, setting, and participantsWe selected patients with mCRPC from the multicenter, randomized, phase 2, randomized, open-label, multicenter study in mCRPC on the pharmacodynamic effects of budesonide on cabazitaxel (Jevtana) (CABARESC). Before the start of the first and third cabazitaxel cycle, CTCs were enumerated using the CellSearch System. In patients with ≥10 CTCs in 7.5ml blood at baseline, the expression of AR-V7 was assessed by quantitative polymerase chain reaction. Outcome measures and statistical analysisThe primary end point was the association between the AR-V7 status and the CTC response rate (decrease to fewer than five CTCs in 7.5ml blood during treatment). Secondary end points were the prostate-specific antigen (PSA) response rate (RR) and overall survival (OS). Analyses were performed using chi-square and log-rank tests. Results and limitationsAR-V7 was detected in 16 of 29 patients (55%) with ≥10 CTCs and was more frequently found in abiraterone pretreated patients (5 of 5 [100%] treated vs 7 of 20 [35%] untreated; p=0.009). We found no differences in CTC and PSA RRs. The presence of AR-V7 in CTCs was not associated with progression-free survival (hazard ratio [HR]: 0.8; 95% confidence interval [CI], 0.4–1.8) or overall survival (HR 1.6; 95% CI, 0.6–4.4). ConclusionsThe response to cabazitaxel seems to be independent of the AR-V7 status of CTCs from mCRPC patients. Consequently, cabazitaxel might be a valid treatment option for patients with AR-V7-positive CTCs. Patient summaryTools are needed to select specific treatments for specific patients at specific times. The presence of the gene AR-V7 in CTCs has been associated with resistance to anti-androgen receptor treatments. We investigated whether this holds true for cabazitaxel, but we found cabazitaxel to be effective independent of the presence of AR-V7.

Efficacy of cabazitaxel in mouse models of pediatric brain tumors.

There is an unmet need in the treatment of pediatric brain tumors for chemotherapy that is efficacious, avoids damage to the developing brain, and crosses the blood-brain barrier. These experiments evaluated the efficacy of cabazitaxel in mouse models of pediatric brain tumors. The antitumor activity of cabazitaxel and docetaxel were compared in flank and orthotopic xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS-PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo spontaneous mouse medulloblastoma tumor model. This study observed significant tumor growth inhibition in pediatric patient-derived flank xenograft tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and CNS-PNET showed significantly improved survival with treatment of cabazitaxel. These data support further testing of cabazitaxel as a therapy for treating human pediatric brain tumors.

Phase I clinical study of cabazitaxel plus prednisolone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in a Japanese population.

237 Background: Cabazitaxel (CBZ), a novel taxoid agent, promotes tubulin assembly and stabilizes microtubules, as docetaxel (DTX). CBZ had antitumor activity in DTX-resistant tumor models in vitro. We assessed dose-limiting toxicities (DLTs), safety and efficacy of CBZ in patients (pts) with mCRPC with prior DTX treatment. Methods: This was an open-label, dose escalation study of CBZ every 3 weeks, with daily prednisolone. Two CBZ dose levels (20 or 25 mg/m2) were set in the dose escalation cohort to determine the maximum tolerated dose (MTD). Pts in the expansion cohort received the MTD. DLTs were evaluated at cycle 1 and were defined as follows: Grade (Gr) 4 neutropenia > 7 days, Gr 4 thrombocytopenia, Gr 4 febrile neutropenia (FN), or Gr 3/4 non-hematological toxicities. Gr 3/4 neutropenia was prospectively studied based on occurrence of Gr 3/4 neutropenia during prior DTX treatment. Results: A total of 48 pts received CBZ (median age 66.1 years; ECOG PS: 0, 34 pts; 1, 14 pts; median cumulative DTX dose 753 mg/m2). None of the evaluable pts in the dose escalation cohort experienced a DLT. All pts had at least one Gr 3/4 adverse event (AE). Frequent Gr 3/4 AEs at 25 mg/m2 were neutropenia (44 pts, 100%) and FN (24 pts, 54.5%). G-CSF prophylaxis was not allowed at cycle 1 and was only used in 10% of cycles from cycle 2 onward. Neutropenia occurrence during prior DTX treatment did not affect neutropenia or FN incidence during CBZ treatment. No pt discontinued CBZ due to neutropenia or FN and no toxic death was reported. In total, 12/41 pts (29.3%) had a PSA response, and 2/12 evaluable pts had a partial response as the best overall response. Conclusions: The safety profile of CBZ in Japanese pts was generally consistent with that reported in previous studies. The cumulative dose of prior DTX was higher and use of G-CSF prophylaxis less frequent than in previous studies, which may have contributed to the increased incidence of neutropenia and FN in Japanese pts. The majority of neutropenia and FN events were manageable and did not lead to treatment discontinuation. In terms of safety and efficacy, CBZ has a favourable risk–benefit profile in Japanese pts with mCRPC following prior DTX therapy. Clinical trial information: NCT01324583.

Sequential Therapies in Castration-Resistant Prostate Cancer

153 ISSN 1479-6694 10.2217/FON.13.243 © 2014 Future Medicine Ltd Future Oncol. (2014) 10(2), 153–155 An unprecedented large number of agents capable of prolonging survival is presently available for patients with castrationresistant prostate cancer (CRPC) [1,2]. Survival expectancy of a patient with newly diagnosed CRPC has approximately doubled since the approval of docetaxel, although it still appears to be poor in selected populations [3,4], such as those with primary refractoriness to docetaxel [5]. US FDAand EMA-approved agents now include immunotherapy agent sipuleucel-T, CYP17A inhibitor abiraterone, antiandrogen receptor enzalutamide, cytotoxic agent cabazitaxel and radiopharmeceutical agent radium-223. These agents were approved in different settings. While sipuleucel-T was mainly tested in minimally symptomatic, chemotherapy-naive patients, abiraterone, enzalutamide and cabazitaxel were tested in patients pretreated with docetaxel. Radium-223 was approved in patients who were either ineligible to or refused or had already received docetaxel, and had symptomatic diffuse bone metastases. Although abiraterone proved to prolong progression-free survival in chemotherapy-naive patients, with a statistically significant improvement in overall survival that did not satisfy the statistical boundaries required by the study design, the potential detrimental effect on survival that postponing docetaxel in a population of metastatic CRPC might have was not adequately accounted for in this trial, and an opportunity to test sequential therapies was missed [6]. With multiple available effective agents, their optimal sequential use, their use in selected populations and the early assessment of efficacy in individual patients are three main issues. A few recently published case series showed only modest efficacy of cabazitaxel, abiraterone and enzalutamide when used as third-line agents, although prospective data are lacking. In 24 patients treated with cabazitaxel after docetaxel and abiraterone, a median of four cycles of cabazitaxel were delivered, with a median survival from initiation of cabazitaxel of 8.2 months (95% CI: 3.34–13.05) [7], and a median survival after docetaxel initiation of 32 months. In 35 patients treated with the sequence enzalutamide after docetaxel and abiraterone, a greater than 50% PSA decline was recorded in 45.7% of patients,

Cabazitaxel in Patients With Metastatic Castration-Resistant Prostate Cancer: Results of a Compassionate Use Program in The Netherlands

BackgroundCabazitaxel has been reimbursed as a second-line therapy for patients with metastatic castrate-resistant prostate cancer (mCRPC) in the Netherlands since 2011. Before reimbursement was available, cabazitaxel was provided through a Compassionate Use Program (CUP). We report the results of the Dutch CUP, detailing the safety and efficacy of cabazitaxel in a routine clinical practice setting. Patients and MethodsSafety and efficacy data of all 5 Dutch centers participating in the cabazitaxel CUP were collected. Safety data were collected prospectively using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3.0. Overall survival (OS) and progression-free survival (PFS), time to PSA progression (TTPP), and best clinical response were evaluated retrospectively. ResultsFifty-one patients were registered in the CUP; 49 received cabazitaxel. Forty-two of 49 patients [85.7%], 42 patients had ≥ 2 metastatic sites. Patients received on average 6 cabazitaxel cycles (range, 1-21). A dose reduction or dose delay occurred in 13 and 20 patients [26.5% and 40.9%] respectively. Prophylactic granulocyte colony-stimulating factor (G-CSF) was used in 8 patients [16.3%]. Grade ≥ 3 adverse events were observed in 25 patients [51.0%]; 16 patients [32.7%] discontinued treatment because of treatment-emergent adverse events (TEAEs). Serious adverse events (SAEs) occurred in 16 (32.7%) patients; the most frequent SAEs were hematuria (4 patients [8.3%]) and urosepsis (3 patients [6.3%]). Febrile neutropenia occurred twice; no patient had grade ≥ 3 neuropathy. No toxicity-related mortality occurred. Median follow-up was 24.1 months. Median OS was 8.7 months (interquartile range [IQR], 6.0-15.9 months); median TTPP was 2.8 months (IQR, 1.7-5.9 months). ConclusionIn the Dutch CUP, patients with advanced mCRPC had delayed tumor progression with acceptable toxicities using cabazitaxel treatment.

Abstract 5055: Efficacy of cabazitaxel in mouse models of pediatric brain tumors.

Abstract Successful treatment of pediatric brain tumors is limited by significant long-term toxicities associated with surgery and radiation therapy on the developing central nervous system There is an unmet need for chemotherapy with improved efficacy in difficult to treat tumors, such as supratentorial primitive neuroectodermal tumors (sPNET) and atypical teratoid/rhabdoid tumors (ATRT), as well as diagnoses that currently have good long-term survival, such as medulloblastoma. Overcoming the blood brain barrier is a large hurdle in effectively treating brain tumors, particularly when there is a need, as with very young patients, to avoid radiation therapy. Cabazitaxel is a promising taxane derivative shown to effectively kill tumor cells in pre-clinical in vitro and in vivo experiments. Similar to docetaxel, cabazitaxel has favorable drug properties and a manageable safety profile in patients with advanced solid tumors, with the advantage of being able to cross the blood brain barrier. Additionally, cabazitaxel has shown efficacy in docetaxel resistant tumors. The experiments presented here, tested the relative efficacy of cabazitaxel and docetaxel in mouse models of pediatric brain tumors. A spontaneous mouse model of medulloblastoma driven by Smo activation was evaluated by magnetic resonance imaging for tumor growth and blood brain barrier integrity before and after treatment with cabazitaxel or docetaxel. Efficacy of cabazitaxel and docetaxel against patient-derived pediatric brain tumors was tested in flank and orthotopic xenograft models of medulloblastoma, sPNET, ATRT, and ependymoma. We observed regression in some flank xenograft tumors after treatment with cabazitaxel or docetaxel, with evidence of superior action of cabazitaxel. These data support further testing of cabazitaxel as a therapy to treat human pediatric brain tumors. This work has been funded by Sanofi Inc. Citation Format: James M. Olson, Emily Girard, Sally Ditzler, Andrew Richards, Doonhoon Lee, Patricia Vrignaud. Efficacy of cabazitaxel in mouse models of pediatric brain tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5055. doi:10.1158/1538-7445.AM2013-5055

Abstract 316: Cabazitaxel antitumor activity in docetaxel-resistant patient-derived prostate cancer xenograft models.

Abstract Introduction: The first line of chemotherapy for castration resistant prostate cancer (CRPC) patients is docetaxel treatment. Continued treatment after progression on docetaxel with cabazitaxel can be very strenuous for patients. Clearly, selection of patients that will benefit from either docetaxel or cabazitaxel treatment would be an essential asset to the management of CRPC. Therefore docetaxel-resistant, CRPC xenografts PC339-DOC and PC346C-DOC were developed. These xenografts were tested for sensitivity to cabazitaxel as an initial step to develop a biomarker gene expression profile of docetaxel resistance and cabazitaxel sensitivity in CRPC. Materials and Methods: PC339 (low sensitivity to docetaxel, log cell kill 0.7) and PC346C (moderate sensitivity to docetaxel, log cell kill 1.0) bearing mice were treated with bolus injections of docetaxel (33 mg/kg) every two weeks until the tumor became resistant. Cabazitaxel efficacy was tested in the resistant xenografts by treating PC339-DOC and PC346C-DOC bearing mice with a single bolus injection cabazitaxel (33 mg/kg). Body weight and tumor volume (TV) were monitored up to 160 days post-treatment. Log cell kill was calculated as measure of antitumor activity, taken into account the tumor growth delay induced by the treatment and the tumor doubling time of the tumor (log cell kill= tumor growth delay / tumor doubling time x 3,32). Log cell kill values of < 0.7 reflect no antitumor activity. Importantly, both naïve and resistant xenografts are lacking expression of docetaxel transporter P-glycoprotein (P-gp/ABCB1/MDR1). Results: PC339-DOC was generated within 4 months after start of docetaxel treatment suggesting some intrinsic resistance against docetaxel. In contrast, PC346C-DOC could be classified as acquired resistance as it took more than one year to develop docetaxel resistance in the naïve PC346C. Cabazitaxel was highly active in PC339-DOC, causing complete regression in 4 out of 5 mice (log cell kill > 2.8) while cabazitaxel lacked antitumor activity in PC346C-DOC (log cell kill 0.20). Conclusion: Cabazitaxel was highly active in a docetaxel-resistant PC339DOC xenograft. Low antitumor activity in PC346C-DOC suggests different mechanisms of resistance in both resistant models and potential cross-resistance between taxanes. The differences between PC339-DOC and PC346C-DOC will allow the development of a biomarker profile to specifically select CRPC patients that could benefit from continued treatment with taxanes. Citation Format: Ellen S. de Morree, Corrina M.A. de Ridder, Herman Burger, Erik A.C. Wiemer, Ron H.J. Mathijssen, Ronald de Wit, Wytske M. van Weerden. Cabazitaxel antitumor activity in docetaxel-resistant patient-derived prostate cancer xenograft models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 316. doi:10.1158/1538-7445.AM2013-316

DGI-022 Cost-Efficacy Analysis of Cabazitaxel For the Treatment of Hormone-Refractory Metastatic Prostate Cancer Patients

Background In combination with prednisone or prednisolone, cabazitaxel is indicated for the treatment of patients with hormone-refractory metastatic prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. Cabazitaxel was evaluated...

Efficacy of cabazitaxel and its relationship with predictors of poor response to second hormonal therapies (2d HT) in metastatic castration-resistant prostate cancer (mCRPC).

137 Background: Potential predictors of low response to 2d HT including new agents have been recently identified: high Gleason score, rapid progression with first androgen deprivation therapy (ADT), chemotherapy lines >1 and low baseline testosterone (T) levels. We evaluated the influence of these factors on the efficacy of cabazitaxel (C), a new taxane developed to overcome docetaxel (D) resistance. Methods: Records of 84 consecutive mCRPC pts (median 67 yrs) treated with C for disease progression on D or after D were retrospectively collected in 8 French centers. Baseline characteristics, disease history, PSA response, overall survival (OS) and radiological or clinical progression-free survival (PFS) were collected. Results: At C initiation, 84% of pts were ECOG 0-1, 59% had pain and 24% received ≥2 prior chemotherapy lines. Metastases were located in bone (93%), lymph nodes (49%) and visceral/soft tissues (9%). Gleason score was 8-10 in 47%, median time to progression with first ADT was 20 months and median T was 0.1 ng/ml. Median number of C cycles received was 6 (range 2-14). Efficacy of C was not influenced by Gleason score, response duration to first ADT, prior number of chemo lines, or baseline T (table). Main grade ≥ 3 toxicities were neutropenia (32%), anaemia (17%), thrombocytopenia (8%), diarrhoea (6%), and febrile neutropenia (5%). There was no grade ≥3 peripheral neuropathy and no toxic death. Conclusions: This retrospective study suggests that C is effective and shows an acceptable safety profile. Efficacy was not influenced by predictors of poor response to 2d HT (high Gleason, short response to first ADT, Number of chemo lines, low T levels). If these results are confirmed in further investigations, cabazitaxel could be proposed whatever the baseline characteristics of mCRPC pts. [Table: see text]

Safety and efficacy of cabazitaxel in the docetaxel-treated patients with hormone-refractory prostate cancer.

Prostate cancer (PC) is one of the most common cancers and is a leading cause of death. Its initial growth is dependent on androgens; most patients show an initial response to hormonal therapy but will experience disease progression when PC becomes resistant to castration. In 2004, two key randomized controlled trials demonstrated a benefit for docetaxel-based regimens in the treatment of men with castration-resistant prostate cancer (CRPC). Cabazitaxel (XRP6258, TXD258, and RPR116258A), a tubulin-binding taxane drug as potent as docetaxel in cell lines, was the first treatment able to prolong survival for metastatic CRPC in the post-docetaxel setting. This review describes pharmacologic parameters of this agent followed by a review of clinical trials involving cabazitaxel. Other available treatments and the place of cabazitaxel in metastatic CRPC setting are discussed.

Cabazitaxel: More Than a New Taxane for Metastatic Castrate-Resistant Prostate Cancer?

The taxanes are recognized as a major class of chemotherapeutic agents; however, mechanisms of innate and acquired resistance can limit their usefulness. Cabazitaxel, a novel taxane with microtubule-stabilizing potency similar to docetaxel, exhibits activity against tumor cell lines resistant to paclitaxel and docetaxel. Cabazitaxel showed linear pharmacokinetics and a terminal elimination half-life comparable with that of docetaxel, findings which support dosing as a single infusion in three-week treatment cycles. Dose-ranging studies recommended doses of 20 or 25 mg/m(2) every three weeks. Antitumor activity was shown in patients with advanced cancer and chemotherapy failure (including taxane failure). Other early studies investigated the efficacy of cabazitaxel in pretreated metastatic breast cancer, either as a single agent or in combination with capecitabine. Objective antitumor response rates of up to 24% and sustained tumor stabilizations were also observed. The TROPIC phase III study, conducted in patients with metastatic castrate-resistant prostate cancer previously treated with docetaxel, established cabazitaxel as the first chemotherapeutic agent to offer a survival advantage in this patient population. Across these studies, the dose-limiting hematologic toxicity was neutropenia (including febrile neutropenia), usually controllable with colony-stimulating factor/granulocyte-colony stimulating factor support.

TROPIC: Phase III Trial of Cabazitaxel for the Treatment of Metastatic Castration-Resistant Prostate Cancer

For patients with metastatic castration-resistant prostate cancer (mCRPC), the current standard of care is chemotherapy involving the tubulin-binding taxane docetaxel. However, as the tumor cells become resistant to docetaxel-based therapy, disease progression is inevitable, and until recently there was no further available treatment beyond palliative care. In June 2010, cabazitaxel, a next-generation taxane, was approved by the US FDA for the treatment of mCRPC that has progressed after docetaxel therapy. This article describes the background and rationale of cabazitaxel's development and the clinical study program that led to its FDA approval, focusing on the Phase III TROPIC trial that demonstrated the efficacy of cabazitaxel plus prednisone in the treatment of mCRPC. Future development of this therapy and others under investigation is discussed.

Cabazitaxel for the treatment of prostate cancer

Introduction: Prostate cancer is a frequently diagnosed male cancer. In men presenting locally advanced or metastatic disease, the mainstay of treatment is hormonal suppression. Despite the castrate levels of testosterone, with time, prostate cancer gradually evolves into a castration-refractory state. Chemotherapeutic agents are able to influence the natural history of metastatic castration-resistant prostate cancer. Docetaxel is a clinically relevant, FDA-approved taxane. Today, it is the first-line chemotherapeutic agent in castration-refractory prostate cancer (CRPC). There is no standard second-line chemotherapeutic regimen.Areas covered: This review provides information on the efficacy of cabazitaxel as a second-line treatment for CRPC. The medline database was searched for clinical trials on chemotherapeutical treatment options of castration-resistant prostate cancer. All available data on the efficacy of cabazitaxel are summarized.Expert opinion: New treatment strategies for castration-resistant prostate cancer should primarily focus on quality of life. In this view, vaccination therapy seems promising because of the acceptable level of toxicity. However, more research is needed to prove their efficacy in the treatment of castration-resistant prostate cancer. Cabazitaxel seems to be a promising second-line therapy in CRPC.