PMID- 26671239
OWN - NLM
STAT- MEDLINE
DCOM- 20161110
LR  - 20181113
IS  - 1432-1041 (Electronic)
IS  - 0031-6970 (Linking)
VI  - 72
IP  - 3
DP  - 2016 Mar
TI  - First-line therapy for non-transplant eligible patients with multiple myeloma: 
      direct and adjusted indirect comparison of treatment regimens on the existing 
      market in Germany.
PG  - 257-65
LID - 10.1007/s00228-015-1998-5 [doi]
AB  - OBJECTIVES: The purpose of this study was to compare approved first-line 
      therapies for patients with multiple myeloma. METHODS: A systematic literature 
      search for phase III randomized controlled trials (RCTs) comparing first-line 
      chemotherapies approved in Germany and recommended by guidelines at the time of 
      study design was conducted. Random-effects meta-analysis (MA) was used for direct 
      and the Bucher method for adjusted indirect treatment comparison. RESULTS: One 
      RCT comparing melphalan and prednisone plus bortezomib (VMP) vs. melphalan and 
      prednisone (MP) and six RCTs comparing MP plus thalidomide (MPT) vs. MP were 
      analysed. For MPT vs. MP, an individual patient data (IPD) MA was used for 
      sensitivity analyses. VMP and MPT were superior to MP regarding efficacy 
      endpoints (VMP vs. MP, overall survival (OS): hazard ratio (HR) 0.70, 95 % 
      confidence interval (CI) 0.57-0.86; progression-free survival (PFS): HR 0.56, 
      0.39-0.79; complete response (CR), risk-ratio (RR) for non-response: 0.70, 
      0.65-0.75; MPT vs. MP, OS: HR 0.83, 0.66-1.03; PFS: HR 0.67, 0.56-0.81; CR, RR 
      for non-response 0.92, 0.88-0.95); but had a higher risk of developing any grade 
      3-4 adverse events (AEs) (VMP vs. MP: RR 1.13, 1.06-1.20; MPT vs. MP: RR 2.06, 
      1.43-2.98). The indirect comparison of VMP vs. MPT via MP showed a statistically 
      not significant advantage for VMP regarding survival outcomes (OS: HR 0.85, 
      0.63-1.14; PFS: HR 0.83, 0.56-1.23) and a significant advantage regarding CR (RR 
      for non-response 0.76, 0.70-0.83) and AEs (RR 0.55, 0.38-0.80). Treatment 
      comparisons using results of IPD MA yielded similar effect sizes. CONCLUSIONS: 
      VMP and MPT seem more effective than MP, VMP was superior to MPT regarding 
      response criteria and AEs. Our results may best be confirmed by a head-to-head 
      trial of VMP vs. MPT.
FAU - Kuhr, Kathrin
AU  - Kuhr K
AD  - Institute of Medical Statistics, Informatics and Epidemiology, University of 
      Cologne, 50924, Koeln, Germany. kathrin.kuhr@uni-koeln.de.
FAU - Wirth, Daniel
AU  - Wirth D
AD  - Janssen-Cilag GmbH, Neuss, Germany.
FAU - Srivastava, Kunal
AU  - Srivastava K
AD  - HERON Health Pvt. Ltd, Chandigarh, India.
AD  - BresMed Health Solutions India Pvt. Ltd, Malbhat, Margao, India.
FAU - Lehmacher, Walter
AU  - Lehmacher W
AD  - Institute of Medical Statistics, Informatics and Epidemiology, University of 
      Cologne, 50924, Koeln, Germany.
FAU - Hellmich, Martin
AU  - Hellmich M
AD  - Institute of Medical Statistics, Informatics and Epidemiology, University of 
      Cologne, 50924, Koeln, Germany.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20151216
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
RN  - 0 (Antineoplastic Agents)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - 69G8BD63PP (Bortezomib)
RN  - Q41OR9510P (Melphalan)
RN  - VB0R961HZT (Prednisone)
SB  - IM
MH  - Antineoplastic Agents/*therapeutic use
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Bortezomib/therapeutic use
MH  - Clinical Trials, Phase III as Topic
MH  - Germany
MH  - Humans
MH  - Melphalan/therapeutic use
MH  - Multiple Myeloma/*drug therapy
MH  - Prednisone/therapeutic use
MH  - Randomized Controlled Trials as Topic
MH  - Thalidomide/therapeutic use
OTO - NOTNLM
OT  - Adjusted indirect treatment comparison
OT  - First-line therapy
OT  - Meta-analysis
OT  - Multiple myeloma
EDAT- 2015/12/17 06:00
MHDA- 2016/11/12 06:00
CRDT- 2015/12/17 06:00
PHST- 2015/09/21 00:00 [received]
PHST- 2015/12/10 00:00 [accepted]
PHST- 2015/12/17 06:00 [entrez]
PHST- 2015/12/17 06:00 [pubmed]
PHST- 2016/11/12 06:00 [medline]
AID - 10.1007/s00228-015-1998-5 [pii]
AID - 10.1007/s00228-015-1998-5 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 2016 Mar;72(3):257-65. doi: 10.1007/s00228-015-1998-5. Epub 
      2015 Dec 16.