Decisions on Further Research for Predictive Biomarkers of High-Dose Alkylating Chemotherapy in Triple-Negative Breast Cancer: A Value of Information Analysis.
OBJECTIVE
To inform decisions about the design and priority of further studies of emerging predictive biomarkers of high-dose alkylating chemotherapy (HDAC) in triple-negative breast cancer (TNBC) using value-of-information analysis.


METHODS
A state transition model compared treating women with TNBC with current clinical practice and four biomarker strategies to personalize HDAC: 1) BRCA1-like profile by array comparative genomic hybridization (aCGH) testing; 2) BRCA1-like profile by multiplex ligation-dependent probe amplification (MLPA) testing; 3) strategy 1 followed by X-inactive specific transcript gene (XIST) and tumor suppressor p53 binding protein (53BP1) testing; and 4) strategy 2 followed by XIST and 53BP1 testing, from a Dutch societal perspective and a 20-year time horizon. Input data came from literature and expert opinions. We assessed the expected value of partial perfect information, the expected value of sample information, and the expected net benefit of sampling for potential ancillary studies of an ongoing randomized controlled trial (RCT; NCT01057069).


RESULTS
The expected value of partial perfect information indicated that further research should be prioritized to the parameter group including "biomarkers' prevalence, positive predictive value (PPV), and treatment response rates (TRRs) in biomarker-negative patients and patients with TNBC" (€639 million), followed by utilities (€48 million), costs (€40 million), and transition probabilities (TPs) (€30 million). By setting up four ancillary studies to the ongoing RCT, data on 1) TP and MLPA prevalence, PPV, and TRR; 2) aCGH and aCGH/MLPA plus XIST and 53BP1 prevalence, PPV, and TRR; 3) utilities; and 4) costs could be simultaneously collected (optimal size = 3000).


CONCLUSIONS
Further research on predictive biomarkers for HDAC should focus on gathering data on TPs, prevalence, PPV, TRRs, utilities, and costs from the four ancillary studies to the ongoing RCT.
Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, The Netherlands.
Anna
A
Miquel-Cases
Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, The Netherlands.
Valesca P
VP
Retèl
Department of Psychosocial Research and Epidemiology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, The Netherlands; Department of Health Technology and Services Research, University of Twente, Enschede, The Netherlands. Electronic address: w.v.harten@nki.nl.
Wim H
WH
van Harten
Hutchinson Institute for Cancer Outcomes Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Lotte M G
LM
Steuten
D000328:Adult; D000477:Alkylating Agents / Q000191:economics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000191:economics / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000191:economics*; D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D018572:Disease-Free Survival; D005260:Female; D006292:Health Priorities / Q000191:economics; D006801:Humans; D008390:Markov Chains; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D062085:RNA, Long Noncoding; D016032:Randomized Controlled Trials as Topic; D012106:Research / Q000191:economics; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000191:economics* / Q000453:epidemiology / Q000628:therapy; D000071857:Tumor Suppressor p53-Binding Protein 1; D044767:Ubiquitin-Protein Ligases / Q000191:economics* / Q000235:genetics
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1; C077885:XIST non-coding RNA; C111164:BRAP protein, human; D044767:Ubiquitin-Protein Ligases
decision modeling; diagnostics; high-dose alkylating chemotherapy; predictive biomarkers; value of information