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Annals of Oncology 24: 2402–2408, 2013 doi:10.1093/annonc/mdt194 Published online 30 May 2013
Impact of cabazitaxel on 2-year survival and palliation of tumour-related pain in men with metastatic castration-resistant prostate cancer treated in the TROPIC trial A. Bahl1,†, S. Oudard2,†, B. Tombal3, M. Özgürog^ lu4, S. Hansen5, I. Kocak6, G. Gravis7, J. Devin8, L. Shen8, J. S. de Bono9* & A. O. Sartor;10 for the TROPIC Investigators‡ 1 Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, UK; 2Department of Medical Oncology, Hôpital Européen Georges Pompidou, René Descartes University, Paris, France; 3Division of Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium; 4Department of Medical Oncology, Cerrahpas¸ a Medical Faculty, Istanbul University, Istanbul, Turkey; 5Department of Oncology, Odense University Hospital, Odense, Denmark; 6Clinic of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic; 7Department of Medical Oncology, Institut Paoli Calmette, Hôpital de Jour, Marseille, France; 8 Department of Biostatistics and Programming, Sanofi, Bridgewater, USA; 9Department of Drug Development, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK; 10Departments of Medicine and Urology, Tulane Cancer Center, Tulane University, New Orleans, USA
Received 17 December 2012; revised 5 April 2013 & 12 April 2013; accepted 15 April 2013
Background: Cabazitaxel significantly improves overall survival (OS) versus mitoxantrone in patients with metastatic castration-resistant prostate cancer after docetaxel failure. We examined patient survival at 2 years and tumour-related pain with cabazitaxel versus mitoxantrone. *Correspondence to: Professor Johann Sebastian de Bono, Department of Drug Development, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey SM2 5PT, UK. Tel: +44-208-722-4028; Fax: +44-208-642-7979; E-mail:
[email protected] †
Joint lead authors/authors contributed equally. Investigators listed in web appendix.
‡
© The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact
[email protected]
Annals of Oncology
original articles
Methods: Updated TROPIC data (cut-off 10 March 2010) were used to compare 2-year survival between treatment groups and assess patient demographics and disease characteristics. Factors prognostic for survival ≥2 years were assessed. Pain and Eastern Cooperative Oncology Group performance status were evaluated in the overall patient population. Results: Median follow-up was 25.5 months. After 2 years, more patients remained alive following cabazitaxel than mitoxantrone [odds ratio 2.11; 95% confidence interval (CI) 1.33–3.33]. Treatment with cabazitaxel was prognostic for survival ≥2 years. Demographics/baseline characteristics were balanced between treatment arms irrespective of survival. Pain at baseline and pain response were comparable between treatment groups. Average daily pain performance index was lower for cabazitaxel versus mitoxantrone (all cycles; 95% CI –0.27 to –0.01; P = 0.035) and analgesic scores were similar. Grade ≥3 peripheral neuropathies were uncommon and comparable between treatment groups. Conclusions: Cabazitaxel prolongs OS at 2 years versus mitoxantrone and has low rates of peripheral neuropathy. Palliation benefits of cabazitaxel were comparable to those of mitoxantrone.The study was registered with www. ClinicalTrials.gov (NCT00417079). Key words: cabazitaxel, symptom relief, palliative care, prostate cancer, treatment response, quality of life
introduction In the past 3 years, several new agents have demonstrated a survival benefit in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel. Cabazitaxel is a next-generation taxane that has preclinical activity against a range of tumour types (Vrignaud, et al. manuscript submitted), the ability to cross the blood–brain barrier (Semiond, et al. manuscript submitted) and a safety profile consistent with other chemotherapies [1–3]. In the phase III TROPIC trial, cabazitaxel plus prednisone/ prednisolone significantly improved overall survival (OS) in patients with mCRPC versus mitoxantrone plus prednisone/ prednisolone, with a 30% reduction in the risk of death [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.59–0.83; P < 0.0001; data cut-off 25 September 2009] [4]. Based on the results of the TROPIC trial, cabazitaxel (25 mg/m2 once every 3 weeks) plus prednisone was approved by the EMA, FDA and other national health authorities for the treatment of men with metastatic ‘hormone-refractory’ prostate cancer whose disease has progressed after receiving a docetaxel-containing regimen [2, 3]. Extended follow-up (cut-off 10 March 2010) demonstrated continued divergence of the survival curves (HR 0.72; 95% CI 0.61–0.84; P < 0.0001) [5]. While the primary aim of therapy for mCRPC is to extend survival, tumour-related pain is associated with increased morbidity, reduced performance status and psychological deterioration [6, 7]. In addition, peripheral neuropathies, a known side-effect of taxanes, can be incapacitating for patients [8]. In this TROPIC trial update, we present follow-up data on the subgroup of patients who survived ≥2 years. Furthermore, we examine the impact of cabazitaxel plus prednisone/prednisolone compared with mitoxantrone plus prednisone/prednisolone on pain, Eastern Cooperative Oncology Group performance status (ECOG PS) and the occurrence of peripheral neuropathies.
patients and methods The design of the TROPIC study has been described previously [4]. The study was registered with ClinicalTrials.gov (NCT00417079).
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We conducted analyses of several pre-specified end points. Patients alive at ≥2 and
