Objective To compile the safety profile and quality of life (QoL) data for patients with metastatic castration‐resistant prostate cancer (mCRPC) treated with cabazitaxel in the UK Early Access Programme (UK EAP). Patients and Methods A total of 112 patients participated at 12 UK cancer centres. All had mCRPC with disease progression during or after docetaxel. Patients received cabazitaxel 25 mg/m2 every 3 weeks with prednisolone 10 mg daily for up to 10 cycles. Safety assessments were performed before each cycle and QoL was recorded at alternate cycles using the EQ‐5D‐3L questionnaire and visual analogue scale (VAS). The safety profile was compiled after completion of the UK EAP and QoL measures were analysed to record trends. No formal statistical analysis was carried out. Results The incidences of neutropenic sepsis (6.3%), grade 3 and 4 diarrhoea (4.5%) and grade 3 and 4 cardiac toxicity (0%) were low. Neutropenic sepsis episodes, though low, occurred only in patients who did not receive prophylactic granulocyte‐colony stimulating factor. There were trends towards improved VAS and EQ‐5D‐3L pain scores during treatment. Conclusions The UK EAP experience indicates that cabazitaxel might improve QoL in mCRPC and represents an advance and a useful addition to the armamentarium of treatment for patients whose disease has progressed during or after docetaxel. In view of the potential toxicity, careful patient selection is important.

Standard first-line treatment for metastatic castration-resistant prostate cancer (mCRPC) is docetaxel plus prednisone; however, patients will usually experience disease progression during or after docetaxel treatment due to inherent or acquired resistance. Before 2010, second-line options for mCRPC were limited. However, cabazitaxel, abiraterone acetate and enzalutamide have since been approved for patients with mCRPC whose disease has progressed during or after receiving docetaxel, based on the Phase III trials TROPIC, COU-AA-301 and AFFIRM. In all three trials, an overall survival benefit (primary endpoint) was seen in the experimental arm compared with the control arm: 15.1 vs. 12.7months for cabazitaxel plus prednisone compared with mitoxantrone plus prednisone in TROPIC (hazard ratio [HR] 0.70; P<0.0001); 14.8 vs. 10.9months for abiraterone acetateplus prednisone compared with placebo plus prednisone in COU-AA-301 (HR 0.65; P<0.001); and 18.4 vs. 13.6months for enzalutamide compared with placebo alone in AFFIRM (0.63; P<0.001). However, differences in patient populations, comparators, and selection and/or definition of secondary endpoints make it difficult to draw direct cross-trial comparisons. Radium-223 dichloride has also been approved for patients with mCRPC with metastases to bone but not other organs. To date, no comparative trials or sequencing studies with newer agents have been performed. Without such data, treatment decisions must be based on evaluation of the existing evidence. This commentary compares and contrasts study designs and key data from each of these Phase III trials, and also discusses recent and ongoing clinical trials with new agents in the first- and second-line settings in mCRPC.

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30 Background: Hormone therapy in combination with radiotherapy is a curative treatment option for prostate cancer (CaP). Neoadjuvant goserelin is known to reduce prostate gland volume by about 26%, such that radiotherapy treatment volumes are smaller, reducing the risk of damage to bladder and rectum. Triptorelin is 100 times more potent than native LHRH and has a longer half life than both native LHRH and goserelin. This study evaluated the equivalence of cytoreductive efficacy of neoadjuvant triptorelin and goserelin. Methods: Seventy-onepatients with localized CaP who have chosen radical radiotherapy had been randomized by stratified block design, toreceive either triptorelin (n=37) or goserelin (n=34) with bicalutamide cover. Prostate volume was measured at baseline and 14 weeks after start of therapy on transrectal ultrasound (TRUS). PSA, testosterone levels, and EQ5D, QLQ-PR25, QLQ-C30 questionnaires were completed at baseline, 6, 10, and 14 weeks after start of therapy. All the patients had subsequent radical radiotherapy and followed up as per departmental protocol. Changes in TRUS volume and time to castrate levels of testosterone were evaluated. Results: The mean (±S.D) baseline prostate volume in the goserelin and triptorelin groups was 38.1(±12.8) cc and 39.4(±17.5) cc, respectively. The mean (±S.D) reduction in the prostate volume after 14 weeks of goserelin and triptorelin was 36.8(±18.4)% and 32.5(±20.9)%, respectively (p=0.36: Analysis of Covariance). Twenty-nine out of 34 in the goserelin group and 33 out of 37 patients in the triptorelin group achieved castrate levels of testosterone (£0.5nmol/L). The median time to castration was 6.1 (95% CI: 5.8-6.5) and 6.4 (95% CI: 5.9-10.0) weeks for goserelin and triptorelin, respectively (p=0.72: log rank). Conclusions: Goserelin and triptorelin both caused a reduction inprostate volume and achieved castrate levels of testosterone. The cytoreductive efficacy of neoadjuvant triptorelin was equivalent (non-inferior) to that of goserelin. To our knowledge, this is the first reported prospective randomized data demonstrating the equivalence of goserelin and triptorelin in the neoadjuvant setting. Clinical trial information: 2008-007028-25.