dc.contributor.author | Smith, M | |
dc.contributor.author | De Bono, J | |
dc.contributor.author | Sternberg, C | |
dc.contributor.author | Le Moulec, S | |
dc.contributor.author | Oudard, S | |
dc.contributor.author | De Giorgi, U | |
dc.contributor.author | Krainer, M | |
dc.contributor.author | Bergman, A | |
dc.contributor.author | Hoelzer, W | |
dc.contributor.author | De Wit, R | |
dc.contributor.author | Bögemann, M | |
dc.contributor.author | Saad, F | |
dc.contributor.author | Cruciani, G | |
dc.contributor.author | Thiery-Vuillemin, A | |
dc.contributor.author | Feyerabend, S | |
dc.contributor.author | Miller, K | |
dc.contributor.author | Houédé, N | |
dc.contributor.author | Hussain, S | |
dc.contributor.author | Lam, E | |
dc.contributor.author | Polikoff, J | |
dc.contributor.author | Stenzl, A | |
dc.contributor.author | Mainwaring, P | |
dc.contributor.author | Ramies, D | |
dc.contributor.author | Hessel, C | |
dc.contributor.author | Weitzman, A | |
dc.contributor.author | Fizazi, K | |
dc.date.accessioned | 2017-03-01T13:53:33Z | |
dc.date.issued | 2016-09-01 | |
dc.identifier.citation | Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016, 34 (25), pp. 3005 - 3013 | |
dc.identifier.issn | 0732-183X | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/457 | |
dc.identifier.eissn | 1527-7755 | |
dc.identifier.doi | 10.1200/jco.2015.65.5597 | |
dc.description.abstract | PURPOSE: Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC. PATIENTS AND METHODS: Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments. RESULTS: A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post-random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively). CONCLUSION: Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes. | |
dc.format | Print-Electronic | |
dc.format.extent | 3005 - 3013 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | LIPPINCOTT WILLIAMS & WILKINS | |
dc.rights.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
dc.subject | Humans | |
dc.subject | Neoplasm Metastasis | |
dc.subject | Anilides | |
dc.subject | Pyridines | |
dc.subject | Prednisone | |
dc.subject | Antineoplastic Agents | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Disease-Free Survival | |
dc.subject | Survival Rate | |
dc.subject | Double-Blind Method | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Male | |
dc.subject | Neoplastic Cells, Circulating | |
dc.subject | Prostatic Neoplasms, Castration-Resistant | |
dc.subject | Biomarkers, Tumor | |
dc.title | Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1. | |
dc.type | Journal Article | |
rioxxterms.versionofrecord | 10.1200/jco.2015.65.5597 | |
rioxxterms.licenseref.uri | https://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.licenseref.startdate | 2016-09 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | |
pubs.issue | 25 | |
pubs.notes | No embargo | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.publication-status | Published | |
pubs.volume | 34 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
dc.contributor.icrauthor | De Bono, Johann | |