Abstract
Background: There has been considerable development in the treatment of advanced prostate cancer over the last decade. A number of agents, including docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and sipuleucel-T, have been reported to improve outcomes in men with castration-resistant disease and their use is being explored in hormone-sensitive prostate cancer. Objectives: To assess the effects of early taxane-based chemohormonal therapy for newly diagnosed, metastatic, hormone-sensitive prostate cancer. Search methods: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, Google Scholar, and Web of Science), trials registries, other sources of grey literature, and conference proceedings, up to 10 August 2018. We applied no restrictions on publication language or status. Selection criteria: We included randomized or quasi-randomized controlled trials in which participants were administered taxane-based chemotherapy with systemic androgen deprivation therapy (ADT) within 120 days of beginning ADT versus ADT alone at the time of diagnosis of metastatic disease. Data collection and analysis: Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model. We rated the quality of evidence according to the GRADE approach. Main results: The search identified three studies in which 2,261 participants were randomized to receive either ADT alone, or taxane-based chemotherapy at a dose of 75mg per square meter of body surface area at three-weekly intervals for six or nine cycles in addition to ADT. Primary outcomes Early treatment with taxane-based chemotherapy in addition to ADT probably reduces death from any cause compared to ADT alone (hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.68 to 0.87; moderate-certainty evidence); this would result in 94 fewer deaths per 1,000 men (95% CI 51 to 137 fewer deaths). We downgraded the certainty of evidence due to study limitations related to potential performance bias. Based on the results of one study with 375 participants, the addition of taxane-based chemotherapy to ADT may increase the incidence of Grade III to V adverse events compared to ADT alone (risk ratio (RR) 2.98, 95% CI 2.19 to 4.04; low-certainty evidence); this would result in 405 more Grade III to V adverse events per 1,000 men (95% CI 243 to 621 more events). We downgraded the certainty of evidence due to study limitations and imprecision. Secondary outcomes Early taxane-based chemotherapy in addition to ADT probably reduces the risk of prostate cancer-specific death (RR 0.79, 95% CI 0.70 to 0.89; moderate-certainty evidence). We downgraded the certainty of evidence due to study limitations related to potential performance and detection bias. The addition of taxane-based chemotherapy also probably reduces disease progression compared to ADT alone (HR 0.63, 95% CI 0.56 to 0.71; moderate-certainty evidence). We downgraded the certainty of evidence because of study limitations related to potential performance bias. The addition of taxane-based chemotherapy to ADT may result in a large increase in the risk of treatment discontinuation due to adverse events (RR 79.41, 95% CI 4.92 to 1282.78; low-certainty evidence). We downgraded the certainty of evidence due to study limitations and imprecision. This estimate is derived from a single study with no events in the control arm but a discontinuation rate of 20% in the intervention arm. Taxane-based chemotherapy may increase the incidence of adverse events of any grade (RR 1.11, 95% CI 1.06 to 1.17; low-certainty evidence). We downgraded our assessment of the certainty of evidence due to very serious study limitations. There may be a small improvement, which may not be clinically important, in quality of life at 12 months with combination treatment (mean difference (MD) 2.85 on the Functional Assessment of Cancer Therapy - Prostate scale, 95% CI 0.13 higher to 5.57 higher; low-certainty evidence). We downgraded the certainty of evidence for study limitations related to potential performance, detection and attrition bias. Authors' conclusions: Compared to ADT alone, the early (within 120 days of beginning ADT) addition of taxane-based chemotherapy to ADT for hormone-sensitive prostate cancer probably prolongs both overall and disease-specific survival and delays disease progression. There may be an increase in toxicity with taxane-based chemotherapy in combination with ADT. There may also be a small, clinically unimportant improvement in quality of life at 12 months with taxane-based chemotherapy and ADT treatment.
| Original language | English (US) |
|---|---|
| Article number | CD012816 |
| Journal | Cochrane Database of Systematic Reviews |
| Volume | 2018 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 15 2018 |
Bibliographical note
Funding Information:therapy and overall survival. How measured: progression measured by clinical evaluation, PSA testing and radiological tests; FACT-P questionnaire used for quality of life Timepoints measured: progression measured for Group A every three weeks while receiving docetaxel then every 3 months; and every 3 months for Group B; quality of life measured at baseline then every 3 months for 12 months Timepoints reported: progression reported as a continuous outcome with medians and Kaplan-Meier curves; all quality-of-life timepoints reported Safety outcomes How measured: National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE; version 3.0 until September 2011 and version 4.0 thereafter) Timepoints measured: at each visit. Timepoints reported: at each visit. Subgroup: a post hoc analysis was conducted based on the volume of metastatic disease The National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and by grants from the Public Health Service. Sanofi provided the docetaxel and a grant to ECOG-ACRIN Dr. Carducci reports personal fees from Sanofi, Amgen, Astellas, and Medivation outside the submitted work. Dr. DiPaola reports other support from Sanofi-Aventis during the conduct of the study. Dr. Dreicer reports personal fees from Millennium, Medivation, Astellas, Bind Pharmaceuticals, Genentech, Roche, and Dendreon outside the submitted work. Dr. Eisenberger reports personal fees from Sanofi outside the submitted work. Dr. Garcia reports grant support and personal fees from Astellas and Bayer, and personal fees from Sanofi outside the submitted work. Dr. Hahn reports grant support from Sanofi-Aventis during the conduct of the study; grant support from Dendreon, grant support and personal fees from OncoGeneX, grant and non-financial support from Millennium, and personal fees from Medivation and Sanofi-Aventis outside the submitted work. Dr. Hussain reports grant support from the SWOG during the conduct of the study. Dr. Liu reports grant support from the University of Wisconsin Carbone Cancer Center during the conduct of the study. Dr. Picus reports grant support from the National Cancer Institute during the conduct of the study. Dr. Sweeney reports grant support from the NCI during the conduct of the study, and personal fees from Sanofi, Janssen, Astellas, Bayer, and Genentech, personal fees and other support from BIND Therapeutics, and other support from Leuchemix outside the submitted work. In addition, Dr. Sweeney reports a patent related to the use of Pathenolide to inhibit cancer (US6890946 B2), issued to Indiana University, and a pending patent related to a Abiraterone plus Cabozantinib combination, held by Exelixis. Dr. Wong reports other support from Sanofi during the conduct of the study; grant support from Pfizer, Medivation, Millennium, and other support from outside the submitted work
Funding Information:
nancial support from Sanofi -Aventis, outside the submitted work. MRSy reports grants and non-financial support from Sanofi -Aventis, grants and non-financial support from Novartis, grants and non-financial support from Pfizer, grants and non-financial support from Janssen, grants and non-financial support from Astellas, during the conduct of the study; and personal fees from Eli-Lilly, outside the submitted work. ST reports other from Sanofi , other support from Astellas, personal fees from Astellas, and other support from Janssen, outside the submitted work. JW reports a paid consultancy for Janssen. Abiraterone acetate was developed at The Institute of Cancer Research, which therefore has a commercial interest in the development of this agent. All other authors declare no competing interests
Funding Information:
Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, NIHR Clinical Research Netwrok, Swiss Group for Clinical Cancer Research GA reports personal fees from Sanofi -Aventis; personal fees and non-financial support from Astellas; personal fees from Novartis; grants, personal fees, and non-financial support from Janssen, personal fees and non-financial support from Roche/Ventana, personal fees and non-financial support from Medivation, personal fees from Millennium Pharmaceuticals, personal fees and non-financial support from Abbott Laboratories, personal fees from Essa Pharmaceuticals, personal fees and non-financial support from Bayer Healthcare Pharmaceuticals, personal fees from Takeda, and grants from AstraZeneca. AJB reports other support from Janssen, Sanofi, and Astellas, outside the submitted work. RC reports personal fees as a Consultant for Sanofi -Aventis, outside the submitted work. SC reports grants and personal fees from Sanofi-Aventis, outside the submitted work. JdB reports advisory boards and paid participation for Sanofi -Aventis. DPD reports grants from Cancer Research UK, during the conduct of the study; personal fees from Takeda Pharmaceuticals, outside the submitted work. TE reports that patients entering this study received docetaxel free of charge (Sanofi) and has previously received per-patient payment for entering patients in other commercial trials investigating docetaxel. JDG reports other support as a local principal investigator for a study of radium-223 in prostate cancer funded by Bayer, and other support as a local principal investigator for a study of LHRH antagonist in prostate cancer funded by Millennium Pharmaceuticals, outside the submitted work. NDJ reports grants and personal fees from Sanofi, and grants and personal fees from Novartis, during the conduct of the study; grants and personal fees from Janssen, grants and personal fees from Astellas, and grants and personal fees from Bayer, outside the submitted work. RJJ reports grants from Sanofi, and grants and non-financial support from Novartis, during the conduct of the study; grants, personal fees, and non-financial support from Sanofi, grants, personal fees, and non-financial support from Novartis, outside the submitted work. MDM reports personal fees from Sanofi, personal fees from Bayer, personal fees from Dendreon, personal fees from Bristol-Myers, and personal fees from Janssen, outside the submitted work. CCP reports personal fees from Sanofi -Aventis, research funding and speaker’s honoraria from Bayer, and Bavarian Nordic and Janssen, outside the submitted work. MKBP reports funding from Cancer Research UK, Medical Research Council, Novartis, Sanofi -Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network (formerly National Cancer Research Network), and SAKK-Swiss Group for Clinical Cancer Research, during the conduct of the study. JMR reports personal fees from Janssen (lecture fee), outside the submitted work. MRSp reports grants and non-financial support from Sanofi - Aventis, grants and non-financial support from Novartis, grants and non-financial support from Pfizer, grants and non-financial support from Janssen, and grants and nonfinancial support from Astellas, during the conduct of the study. JS reports support for travel and speakers fees for the following companies in the field of prostate cancer, not related to this paper: Janssen Bayer and Astellas. SS reports personal fees and non-fi-
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© 2018 The Cochrane Collaboration.
