Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study
Language English Country England, Great Britain Media print-electronic
Document type Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
24055414
DOI
10.1016/s1470-2045(13)70398-x
PII: S1470-2045(13)70398-X
Knihovny.cz E-resources
- MeSH
- Bortezomib MeSH
- Drug Resistance, Neoplasm drug effects MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Boronic Acids administration & dosage MeSH
- Hydroxamic Acids administration & dosage MeSH
- Middle Aged MeSH
- Humans MeSH
- Neoplasm Recurrence, Local drug therapy mortality pathology MeSH
- Survival Rate MeSH
- Multiple Myeloma drug therapy mortality pathology MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Antineoplastic Combined Chemotherapy Protocols therapeutic use MeSH
- Pyrazines administration & dosage MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Neoplasm Staging MeSH
- Vorinostat MeSH
- Salvage Therapy * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial, Phase III MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
- Names of Substances
- Bortezomib MeSH
- Boronic Acids MeSH
- Hydroxamic Acids MeSH
- Pyrazines MeSH
- Vorinostat MeSH
BACKGROUND: We aimed to assess efficacy and tolerability of vorinostat in combination with bortezomib for treatment of patients with relapsed or refractory multiple myeloma. METHODS: In our randomised, double-blind, placebo-controlled, phase 3 trial, we enrolled adults (≥18 years) at 174 university hospitals in 31 countries worldwide. Eligible patients had to have non-refractory multiple myeloma that previously responded to treatment (one to three regimens) but were currently progressing, ECOG performance statuses of 2 or less, and no continuing toxic effects from previous treatment. We excluded patients with known resistance to bortezomib. We randomly allocated patients (1:1) using an interactive voice response system to receive 21 day cycles of bortezomib (1·3 mg/m(2) intravenously on days 1, 4, 8, and 11) in combination with oral vorinostat (400 mg) or matching placebo once-daily on days 1-14. We stratified patients by baseline tumour stage (International Staging System stage 1 or stage ≥2), previous bone-marrow transplantation (yes or no), and number of previous regimens (1 or ≥2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed adverse events in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number 00773747. FINDINGS: Between Dec 24, 2008, and Sept 8, 2011, we randomly allocated 317 eligible patients to the vorinostat group (315 of whom received at least one dose) and 320 to the placebo group (all of whom received at least one dose). Median PFS was 7·63 months (95% CI 6·87-8·40) in the vorinostat group and 6·83 months (5·67-7·73) in the placebo group (hazard ratio [HR] 0·77, 95% CI 0·64-0·94; p=0·0100). 312 (99%) of 315 patients in the vorinostat group and 315 (98%) of 320 patients in the placebo group had adverse events (300 [95%] adverse events in the vorinostat group and 282 [88%] in the control group were regarded as related to treatment). The most common grade 3-4 adverse events were thrombocytopenia (143 [45%] patients in the vorinostat group vs 77 [24%] patients in the placebo group), neutropenia (89 [28%] vs 80 [25%]), and anaemia (53 [17%] vs 40 [13%]). INTERPRETATION: Although the combination of vorinostat and bortezomib prolonged PFS relative to bortezomib and placebo, the clinical relevance of the difference in PFS between the two groups is not clear. Different treatment schedules of bortezomib and vorinostat might improve tolerability and enhance activity. FUNDING: Merck.
Alfred Hospital Monash University Melbourne VIC Australia
Dana Farber Cancer Institute Boston MA USA
Department of Clinical Therapeutics University of Athens Athens Greece
Division of Hematology University of Turin Turin Italy
Hackensack University Medical Center Hackensack NJ USA
Hôpital Huriez Serv Maladies du Sang Lille France
Hospital Clinic Barcelona Spain
Merck Whitehouse Station NJ USA
Middlemore Hospital Auckland New Zealand
Nottingham University Hospitals Nottingham UK
Santa Casa de São Paulo São Paulo Brazil
Universitätsklinikum Heidelberg Heidelberg Germany
University Hospital Brno Brno Czech Republic; University of Ostrava Ostrava Czech Republic
Winship Cancer Institute Emory University School of Medicine Atlanta GA USA
References provided by Crossref.org
European perspective on multiple myeloma treatment strategies in 2014
ClinicalTrials.gov
NCT00773747