Cycles Of Cabazitaxel Research Articles

Atypical Haemolytic Uraemic Syndrome Associated with Cabazitaxel in Advanced Prostate Cancer

Atypical haemolytic uraemic syndrome, (aHUS) is a rare but potentially lifethreatening condition with clinical manifestations of haemolytic anaemia, thrombocytopenia, and renal failure. We report the first case of aHUS secondary to cabazitaxel in the setting of metastatic castrate resistant prostate cancer. In July 2015, a 73 year old male presented with acute on chronic back pain, in the context of metastatic castrate-resistant prostate cancer with known pulmonary and skeletal metastases. He was day 3 into his first cycle of cabazitaxel. Within 24 hours of admission, he acutely deteriorated with progressive drowsiness and the development of an acute kidney injury. During this period, he developed acute thrombocytopenia, falling to 58 x 109/L and haemolytic anaemia. He had a coagulopathy, with an elevated INR 1.5, but with a normal APTT and fibrinogen levels. He was subsequently diagnosed with an atypical haemolytic uraemic syndrome. In light of his rapid decline and poor prognosis he was managed with conservative treatment. Over the next 24 hours, he developed progressive acute renal failure and ongoing haemolysis. There was further neurological deterioration which culminated in his passing away three days following his initial presentation. With the

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.

A retrospective analysis of clinical factors influencing response to treatment with cabazitaxel in patients with metastatic castration resistant prostate cancer.

281 Background: The TROPIC trial demonstrated that cabazitaxel improves overall survival (OS) in mCRPC patients progressing on or after docetaxel; a setting where both abiraterone and enzalutamide are also approved. We evaluated baseline factors that may help predict prostate specific antigen (PSA) response or PSA progression defined as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria and OS in mCRPC patients treated with cabazitaxel. Methods: Forty patients from five centres participated in an early access program and were retrospectively reviewed to capture baseline characteristics, disease history, prior and subsequent treatments, PSA response, and OS. The influence of selected variables on PSA response and OS were evaluated by univariate and multivariate stepwise regression analysis. Results: At cabazitaxel initiation, median age was 65, ECOG 0-1 (90%), median PSA was 216 ng/mL, 25% had visceral disease and 70% had pain. Median number of prior docetaxel cycles was 9 and median time from treatment was 9.6 months (5-14.2). Median number of cabazitaxel cycles was 7 (1-27). Fourteen patients received abiraterone before cabazitaxel. In patients with prior abiraterone treatment there was no impact on PSA response compared to patients with no prior abiraterone. In the multivariate regression analysis, presence of visceral disease, low albumin (≤40g/L), low hemoglobin (<100 g/L) and longer time between last docetaxel dose and start of cabazitaxel were correlated with PSA response to cabazitaxel (p<0.10). Age < 65, BMI ≥ 30kg/m2 and presence of pain were linked to an increased likelihood of PSA progression. None of the factors selected were significantly associated with OS. Conclusions: In routine clinical practice, this study suggests that mCRPC patients with visceral disease and a longer time elapsed between last docetaxel dose and start of cabazitaxel may experience a greater PSA response with cabazitaxel.

Rapidly progressive disease in a castration-resistant prostate cancer patient after cabazitaxel discontinuation

We report the case of a 51-year-old patient with metastatic prostate cancer at diagnosis and primary refractoriness to both androgen ablation therapy and docetaxel. At the time of cabazitaxel initiation, the patient had only osseous metastases and was constrained to a wheelchair because of bone pain. Ten cycles of cabazitaxel were administered, and a remarkable response was achieved, with improvement in biochemical markers, performance status, and bone scan findings. Two months after suspension of treatment by choice, the patient developed jaundice because of massive hepatic metastases and died after a few days because of hepatic failure.

Cabazitaxel for metastatic castration-resistant prostate cancer: safety data from the Spanish expanded access program

Background: Based on the TROPIC study results, cabazitaxel was approved for the management of metastatic castration-resistant prostate cancer (mCRPC) progressing on or after docetaxel.Methods: This multi-centre program provided early access to cabazitaxel to patients with mCRPC before its commercialization. Safety data from 153 Spanish patients receiving cabazitaxel 25 mg/m2 i.v. Q3W, plus oral prednisone/prednisolone 10 mg daily, are reported.Results: Median age of patients was 70 years (26.8% ≥ 75 years), 94.1 and 26.8% had bone and visceral metastasis, respectively. Most had an Eastern Cooperative Oncology Group ≤ 1 (88.9%) and had received a median of 8.0 cycles of last docetaxel treatment. The median of cabazitaxel cycles and cumulative dose were 6.0 (Interquartile range [IQR]: 4.0; 8.0) and 148.9 (IQR: 98.2; 201.4) mg/m2, respectively. Adverse events (AEs) possibly related to cabazitaxel occurred in 143 (93.5%) patients. The most frequent grade ≥ 3 AEs were neutropenia (n = 25, 16.3%) and asthenia (n = 17, 11.1%). Febrile neutropenia and grade ≥ 3 diarrhea occurred in 5.2% of the patients each. There were five (3.3%) possibly treatment-related deaths, mainly infection-related. G-CSFs were used in 114 (74.5%) patients, generally as prophylaxis (n = 107; 69.9%). Grade ≥ 3 peripheral neuropathy and nail disorders were uncommon.Conclusions: Cabazitaxel administration, in a real-world setting, is tolerated by Spanish patients with mCRPC, and the AEs are manageable.

Real-world Cabazitaxel Safety: The Italian Early-Access Program in Metastatic Castration-Resistant Prostate Cancer

Cabazitaxel is a novel taxane that is approved for use in metastatic castration-resistant prostate cancer based on the Phase III TROPIC study, which showed improved overall survival with cabazitaxel/prednisone versus mitoxantrone/prednisone. A global early-access program was initiated in order to provide early access to cabazitaxel in docetaxel-pretreated patients and to obtain real-world data. We report interim safety results from an Italian prospective, single-arm, multicenter, open-label trial of 218 patients receiving cabazitaxel 25 mg/m2 every 3 weeks plus prednisolone 10 mg/day, until disease progression, unacceptable toxicity, investigator's decision or death. Patients completing treatment received a median of six cabazitaxel cycles. The most common grade 3/4 adverse events were neutropenia (33.9%), leukopenia (15.6%), anemia (6%) and asthenia (6%). No peripheral neuropathy or nail disorders were observed. These results confirm that cabazitaxel has a manageable safety profile in daily clinical practice and support its use in patients with prostate cancer who progress during or after a docetaxel-based therapy.

DI-101 Cabazitaxel: effectiveness and safety in metastatic prostate cancer

BackgroundCabazitaxel has been approved as combination treatment with prednisone in patients with metastatic prostate cancer (MPC) refractory to hormone treatment previously treated with docetaxel.PurposeTo analyse the effectiveness and safety of...

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,

Meaningful survival after cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC): The Spanish experience.

235 Background: New emerging therapies for metastatic castration resistant prostate cancer (mCRPC), such as cabazitaxel (CBZ), have prompted the need to identify appropriate patients (pts) for each specific treatment. We describe preliminary data on the experience with CBZ in patients (pts) with mCRPC in Spain. Methods: Medical records from docetaxel-resistant mCRPC pts receiving CBZ at 15 centers in Spain were reviewed retrospectively. Baseline characteristics, PSA response, overall survival (OS), radiographic progression-free survival (rPFS), and toxicity were collected. Results: Data from 79 consecutive pts (median age 70) were reviewed: Eastern Cooperative Oncology Group (ECOG) zero to one (87.3%), Gleason score of 7 to 10 (87.1%), visceral involvement (24.1%), pain (74.7%), and radiological progression (68.4%) at CBZ initiation. Median duration of response to first-line androgen deprivation therapy was 20.8 months (mo). Most pts received less than or equal to two hormonal lines (72.2%) and only one docetaxel line (74.7%) before CBZ. Thirty-five (44.3%) pts had progressed on docetaxel. Progression less than six mo or greater than six mo after last docetaxel treatment was observed in 23 (29.1%) and 21 (26.6%) pts, respectively. New hormonal agents (abiraterone or enzalutamide) were given before CBZ in 2.5% of pts and after CBZ in 17.7%. Pts received a median of seven cycles (range 2 to 22) of CBZ. CBZ dose-reductions or -delays for any cause occurred in eight (10.1%) and 20 (25.3%) pts, respectively. Prophylactic G-CSF was given in 32 (40.5%) pts. A PSA decrease of greater than or equal to 50% and greater than or equal to 30% was reached in 41.2% and 48.6% of pts treated with CBZ. Median OS from first CBZ cycle was 16.2 [CI: 10.4;-] mo and median clinical and/or radiographic progression-free survival (rPFS) was 9.9 mo [CI: 7.4; 13.1]. Fourteen (17.7%) pts experienced at least one grade greater than or equal to 3 treatment-related AE, the most common being neutropenia (n=4), febrile neutropenia (n=2), asthenia (n=4), and diarrhoea (n=2). No grade greater than or equal to 3 peripheral neuropathy was reported. An analysis of factors predicting outcome will be presented. Conclusions: CBZ administered in real-life practice and in the adequate treatment setting in Spain is associated with meaningful PFS and OS and an acceptable safety profile. Dose delays and reductions were low. Prophylactic G-CSF use in 4 out of 10 pts may have contributed to these good results.

Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer: Results of the European compassionate-use programme

BackgroundCabazitaxel/prednisone has been shown to prolong survival versus mitoxantrone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel. Subsequently, compassionate-use programmes (CUPs) and expanded-access programmes (EAPs) were established worldwide, allowing access to cabazitaxel before its commercial availability. Preliminary results of the European CUP/EAP, focusing on the elderly population (aged ⩾70years), are reported. Patients and methodsEnrolled patients with progressive mCRPC received cabazitaxel (25mg/m2) plus 10mg oral prednisone/prednisolone every 3weeks until disease progression, death, unacceptable toxicity or physician/patient decision. Safety was analysed by age group (<70, 70–74 and ⩾75years). The influence of selected variables on grade ⩾3 neutropenia and/or neutropenic complications was analysed in multivariate analysis. Results746 men were enrolled (<70years, n=421; 70–74, n=180, ⩾75years, n=145). Number of cabazitaxel cycles, dose reductions for any cause, dose delays possibly related to cabazitaxel adverse events, and tolerability were similar in the three age groups. Prophylactic granulocyte colony-stimulating factor (G-CSF) use was more common in men aged ⩾70years. In multivariate analysis, age ⩾75years, treatment cycle 1, and neutrophil count <4000/mm3 before cabazitaxel injection were associated with increased risk of developing grade ⩾3 neutropenia and/or neutropenic complications. Prophylactic use of G-CSF at a given cycle significantly reduced this risk by 30% (odds ratio 0.70, p=0.04). ConclusionThe results suggest that cabazitaxel has a manageable safety profile in everyday clinical practice. Prophylactic use of G-CSF, especially at cycle 1 and in men aged ⩾75years, is important and improves tolerability in senior adults treated with cabazitaxel.

Beyond ten cycles of cabazitaxel for castrate-resistant prostate cancer.

Background: There are limited data regarding cabazitaxel use beyond 10 cycles. Patients and Methods: Retrospective analysis of prospectively collected data of patients with metastatic castrate-resistant prostate cancer who received over 10 cycles of cabazitaxel after docetaxel failure. Results: Four patients received between 14 and 27 cycles. Reasons for stopping cabazitaxel were toxicity (2), progression (1) and logistics (1). Two of the three patients with measurable disease attained a partial remission (PR). Three patients continued to have a PSA response after 10 cycles; PSA nadir occurred between 17 and 23 cycles. Other than peripheral neuropathy (PN), all the cabazitaxel-related toxicities occurred after the initial cycles and did not increase cumulatively. Clinically significant neuropathy occurred after 15-17 cycles. The cabazitaxel-induced PN was partially reversible, with improvement from grade 3 to grade 2 after a 3-5-month long drug holiday. Conclusion: Cautiously continuing cabazitaxel until progression or intolerable toxicity may maximize efficacy.

Activity of Cabazitaxel in Castration-resistant Prostate Cancer Progressing After Docetaxel and Next-generation Endocrine Agents

BackgroundCabazitaxel, abiraterone, and enzalutamide are survival-prolonging treatments in men with castration-resistant prostate cancer (CRPC) progressing following docetaxel chemotherapy. The sequential activity of these agents has not been studied and treatment sequencing remains a key dilemma for clinicians. ObjectiveTo describe the antitumour activity of cabazitaxel after docetaxel and next-generation endocrine agents. Design, setting, and participantsWe report on a cohort of 59 men with progressing CRPC treated with cabazitaxel, 37 of whom had received prior abiraterone and 9 of whom had received prior enzalutamide. Outcome measurements and statistical analysisChanges in prostate-specific antigen (PSA) level were used to determine activity on abiraterone, enzalutamide, and cabazitaxel treatment. Radiologic tumour regressions according to Response Evaluation Criteria in Solid Tumors (RECIST) and symptomatic benefit were evaluated for cabazitaxel therapy. Results and limitationsThe post–endocrine-therapy patients received abiraterone (n=32), sequential abiraterone and enzalutamide (n=5) or enzalutamide (n=4). These patients received a median of 7 mo of abiraterone and 11 mo of enzalutamide. A median of six cabazitaxel cycles (range: 1–10 cycles) were delivered, with ≥50% PSA declines in 16 of 41 (39%) patients, soft tissue radiologic responses in 3 of 22 (14%) evaluable patients, and symptomatic benefit in 9 of 37 evaluable patients (24%). Median overall survival and progression-free survival were 15.8 and 4.6 mo, respectively. Antitumor activity on cabazitaxel was less favourable in the abiraterone- and enzalutamide-naïve cohort (n=18), likely reflecting biologic differences in this cohort. These data were obtained from a retrospective analysis. ConclusionsThis is the first report of cabazitaxel activity in CRPC progressing after treatment with docetaxel and abiraterone or enzalutamide. We demonstrate significant cabazitaxel activity in this setting. Patient summaryWe looked at the antitumour activity of the chemotherapy drug cabazitaxel in men previously treated with docetaxel chemotherapy and the hormonal drugs abiraterone and enzalutamide. Cabazitaxel appeared active when given after abiraterone and enzalutamide. We can reassure men that cabazitaxel can be used after these novel endocrine treatments.

Potential Value of Gleason Score in Predicting the Benefit of Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer

This study aimed to identify predictive/prognostic factors in castration-resistant prostate cancer patients treated with cabazitaxel. Patients were enrolled from March 2011 to December 2011 in an international expanded access program. In January 2012, when cabazitaxel became commercially available, a prospective study was initiated at University Federico II of Naples and at Rionero in Vulture Hospital. Forty-seven patients were enrolled in this study. Patients received a median of nine cycles of cabazitaxel. Median progression-free survival was 7.0 months (95% CI: 5.7-8.0). Seventeen patients were still alive at the time of the analysis, with a median overall survival of 14 months (95% CI: 11-16). At multivariate analysis, a higher Gleason score (≥ 8) appeared to be associated with prolonged progression-free survival (hazard ratio: 0.36; 95% CI: 0.18-0.72); however, the higher Gleason score showed no statistical impact on overall survival. We hypothesize that the Gleason score has the potential to be incorporated in the clinical decision-making process for definition of treatment strategy in docetaxel-pretreated castration-resistant prostate cancer patients. We encourage further experimentation in this setting.

Quality of life (QoL) of patients with metastatic castration resistant prostate cancer (mCRPC) treated with cabazitaxel.

e16088 Background: The effects of cabazitaxel on QoL, pain response and preference/utility data have not been well studied in men with CRPC treated post-docetaxel. As part of a single-arm multicenter Sanofi-funded Early Access Program (EAP) for cabazitaxel, QoL data were collected on Canadian patients. Methods: Between May 2011 and February 2012, 61 patients (pts) were enrolled at 9 centers. QoL was assessed at the start of each cycle using the FACT-P and its subscales, and the EQ 5D-3L. EQ 5D-3L health state index (HIS) data were converted into utility values (Canadian tariff, Bansback 2011). Present pain intensity (PPI) and analgesic scores were assessed using the McGill-Melzack questionnaire. Results: QoL data were evaluable in 55 pts. Baseline pt characteristics were: median age 65 years (range, 42-79), 92.7% of pts were ECOG PS 0 or 1, 87% had bone metastases, and 56% (31/55) received at least 6 cycles of cabazitaxel. Statistically significant changes from baseline in mean QoL scores were observed on FACT-P total score at cycle 2, and prostate cancer specific subscale (PCS) at cycles 1 to 4. As a measure of QoL response, increases were observed and maintained for &gt; 2 consecutive cycles in 9% (&gt;16 points) and 25% (≥10) of pts for FACT-P total score. Improvements to the level of Minimal Important Differences (MID) (Cella 2009) maintained for &gt; 2 consecutive cycles were observed in 36% of pts for FACT-P total score (MID=6), 49% for PCS subscale (MID=2), and 26% for PCS-Pain subscale (MID=2), respectively. The percentage of pts reporting "no problem" in the EQ-5D pain/discomfort domain were above baseline levels at every cycle and improved from baseline to end of treatment from 19% to 29% (p &lt; 0.05). Other EQ-5D dimensions (anxiety/depression, mobility, self-care and usual activities) remained stable over the course of treatment. Improvement from baseline in utility value (HIS) was observed at cycle 4 with a utility value of 0.769 (vs 0.713 at baseline). PPI scores improved despite stable analgesic use and were significantly different from baseline at cycles 2, 4 and 9. Conclusions: Data from this EAP suggest improvements in QoL, pain and prostate cancer specific symptoms with second-line cabazitaxel treatment. Clinical trial information: NCT01254279.

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.

Management of Post-orchidectomy Stage I Classical Seminoma: 11 Year Outcome Data of a Regional Cancer Unit

Aim: The TROPIC trial [1] demonstrated improved overall survival in patients with metastatic castration-resistant prostate cancer who had progressed during or after treatment with docetaxel. The trial established cabazitaxel as a tolerable and viable second-line treatment option in these patients. We reportourexperience with cabazitaxel inpatients receiving treatment within the Early Access Programme (EAP) and via the Cancer Drugs Fund (CDF). Materials and methods: Retrospective review of patients receiving cabazitaxel chemotherapy from 1 January 2011 to1 January2012. Patients were identified using the pharmacy database. Chemotherapy administration was corroborated via the electronic prescribing system. Patient records provided documentation regarding disease response and treatment toxicities. For patients within the EAP, data were confirmed and supplemented via the Trials Office. Results: 22 patients were identified, of whom 20 received cabazitaxel. 12 patients were treated within the EAP and 8 received cabazitaxel via the CDF. Median age was 68.5 years for the EAP group and 70 years for the CDF group. Median number of cycles was 6 for the EAP and 5.5 for the CDF patients, respectively. Primary GCSF was received by 91.6% of EAP patients and by 75% of CDF patients. Overall, 3/20 patients had treatment discontinued due to progressive disease (after a minimum of 3 cycles of cabazitaxel). 13/20 patients derived a positive biochemical and/or clinical response from treatment. There were no treatment-related deaths. Notable treatment-related adverse events for all patients included: diarrhoea (40%), fatigue (25%), neutropenic sepsis (10%) and thrombocytopenia (5%). Our results are comparable with the TROPIC data [1], which reported the following results: diarrhoea (37%), fatigue (47%), neutropenic sepsis (8%), thrombocytopenia (46%) as well as peripheral neuropathy (14%) and cardiotoxicity (1%). Conclusion: Our results are comparable with the TROPIC data, suggesting cabazitaxel has an acceptable toxicity profile with demonstrable treatment response. Reference

Response to cabazitaxel in CRPC patients previously treated with docetaxel and abiraterone acetate.

155 Background: Cabazitaxel, which is a tubulin-binding chemotherapy, and the CYP-17 androgen biosynthesis inhibitor abiraterone acetate (AA) are both approved for patients with metastatic castration resistant prostate cancer (CRPC) following docetaxel chemotherapy. Recent preclinical data suggest that taxanes impact AR signalling and could imply cross-resistance between new AR targeting treatments and taxane chemotherapy. The aim of this study is to evaluate the antitumor activity of cabazitaxel after AA. Methods: We retrospectively evaluated antitumor activity of cabazitaxel in patients (pts) with metastatic CRPC and progressive disease after docetaxel and AA. Radiological response by RECIST, PSA response by PCWG2 criteria and symptomatic benefit were examined. Results: 89 pts were treated with third-line cabazitaxel, after docetaxel (median 8 cycles; range: 4-12), and AA (median duration of treatment 4.8 months, range: 1-55 months). At cabazitaxel initiation median age was 68 years (range: 53-83), ECOG performance status was 0 or 1 in 70% of pts, and median PSA was 309 ng/ml (range: 3.75-9150). Bone, lymph node and visceral metastases were present in 80 pts (89%), 37 pts (41%), and 12 pts (13%) respectively. An average of 6 cycles of cabazitaxel (range 1-15) were administered. All pts had PSA data available and 44 (49%; 95% CI 39-60%) had a 50% or greater PSA decline. In the 35 pts with RECIST evaluable disease, 7 (20%; 95% CI 8-37%) had a partial response. Conclusions: In men with metastatic CRPC cabazitaxel appears to retain activity in the third-line setting following docetaxel and AA.

Peg-filgrastim and cabazitaxel in prostate cancer patients

To determine the impact of prophylaxis with granulocyte-colony stimulating growth factor (G-CSF) on the risk of febrile neutropenia in a cohort of patients enrolled at the University Federico II of Naples and treated with cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC). We carried out a retrospective review of prospectively collected data of patients enrolled at our institution in a compassionate-use programme with cabazitaxel, aimed at providing early access to the drug before its commercial availability in mCRPC patients. Besides baseline clinical and demographic characteristics, data on treatment efficacy and toxicity, as well as those on the use of G-CSF per patient per cycle were extracted. Progression-free survival and overall survival were calculated using the Kaplan-Meier method. Fisher's exact test was used to explore a relationship between a single event of grade 3 or more neutropenia or febrile neutropenia and previous use of G-CSF. Univariate analysis was carried out to evaluate predictors of grade 3 or more neutropenia and/or febrile neutropenia. Of 34 patients enrolled at our institution from December 2010 to December 2011, 32 had received at least one dose of cabazitaxel and were included in the analysis. Patients received a median of 10 cabazitaxel cycles. Grade 3 or more neutropenia was common, occurring in 64.5% of patients. Three patients (9.3%) developed febrile neutropenia. Twenty-seven patients received prophylaxis with G-CSF during at least one cycle using peg-filgrastim. The risk of grade 3 or more neutropenia and/or febrile neutropenia per patient and per cycle was seven times lower when G-CSF was used. Baseline neutrophil count of less than 4570/mm was the strongest predictor of grade 3 or more neutropenia and/or febrile neutropenia. No toxic death was reported. Only one patient discontinued cabazitaxel because of an adverse event. Our analysis suggests that prophylaxis with peg-filgrastim may considerably reduce the incidence of grade 3 or more neutropenia and, possibly, of febrile neutropenia in mCRPC patients treated with cabazitaxel. Further analyses involving a larger population are warranted to confirm our results.

PCN46 Cost-Efficacy Analysis of Licensed Drugs for the Treatment of Metastatic Castrate Resistant Prostate Cancer Post Docetaxel Based on Hospital Drug Evaluation Methodology in Spain

To estimate which is the dominant treatment between the only two drugs that had been able to demonstrate overall survival (OS) improvements in patients with metastatic castrate resistant prostate cancer (mCRPC) that have progressed on or after docetaxel treatment, and that were approved by the EMA in 2011 (AA by accelerated procedure): cabazitaxel (CBZ) and abiraterone acetate (AA),. We replicated the methodology most commonly used by Spanish hospitals to estimate the cost-efficacy of oncologic drugs (OS gains and incremental costs vs. those of comparators) by: (i) taking the perspective of the Spanish NHS (ii) estimating treatment costs based on the product labels (i.e. main medication, co-medication, premedication, and primary prophylaxis) at ex-factory prices, and the cost of administering such medications; and (iii) the OS data from the respective pivotal phase III trials: for CBZ vs. mitoxantrone + prednisone (MP) OS was 15.1 vs. 12.7 months. For AA vs. placebo + prednisone (PP) OS was 15.8 vs. 11.2. Input for the base case analysis comes from Phase III randomized clinical trials and from publicly available cost data. Sensitivity analysis was performed on: (i) length of treatment; (ii) median OS; and (iii) G-CSF usage and drug administration costs. In our base case scenario the cost per cycle of CBZ was 4,711.52€ vs. 78.20€ for MP. The cost per cycle of AA was 3,179.26€ vs. 11.85€ for PP. Treatment costs difference for CBZ vs. MP is 27,799.93€ (range 13,665.36€ – 46,646.01€) and for AA vs. PP is 25,386.71€ (range 12,669.65€ - 38,103.76€). OS gain is 2.4 months for CBZ and 4.6 months for AA. In Spain, based on local hospital methodology, AA would be the dominant alternative (higher OS gain and lower incremental cost) to treat mCRPC patients that have progressed on or after a docetaxel based regime.

956 - Health-Related Quality of Life (QOL) in Patients with Metastatic Castration-Resistant Prostate Cancer (MCRPC): Cabazitaxel Early Access Program (EAP) Interim Results from Canada

ABSTRACT Background QoL and preference/utility data have not been extensively collected in post-docetaxel (D) mCRPC. Canada collected EQ-5D-3L data in this setting as part of the single-arm multicenter EAP for Cabazitaxel. Methods Between May 2011 and February 2012, 61 evaluable patients (pts) were enrolled at 9 centers. EQ–5D-3L data was collected and analyzed at baseline and after every cycle. EQ-5D health state index (HIS) and visual analog scale (VAS) data were collected. HIS data were converted into utility values using the UK tariff from Dolan 1997. The relationship between baseline ECOG performance status (PS) and EQ-5D values (HIS and VAS) across visits was examined. Results At time of abstract submission, baseline characteristics and EQ-5D data were available for 58 pts: median age 65 years, 94% of pts ECOG PS 0 or 1, 85% had bone metastases, and 45% received at least 6 cycles of cabazitaxel. Significant improvements (p Conclusions Improvements were seen on the EQ-5D in the Pain domain, with more than a third of pts reaching a MID on the EQ-5D by cycle 6. Improvements in pain, a common symptom in mCRPC, directly impact pts' experience of their disease. The poster will present updated data. Disclosure F. Saad: Dr Fred Saad sits on the advisory board for Sanofi Canada and has received consultant's honoraria from Sanofi Canada. He is involved in research projects with Sanofi Canada. E. Winquist: Dr Eric Winquist has received travel funding and consultant's honoraria from Sanofi Canada. He is involved in research projects with Sanofi Canada, M. Girard: Employee with Sanofi Canada, S.S. Sridhar: Dr S.S. Sridhar sits on Advisory Boards and receives Research Funding from Sanofi Canada.