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Comparative Efficacy of Ibrutinib Versus Obinutuzumab + Chlorambucil in First-Line Treatment of Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison

INTRODUCTION: Ibrutinib (ibr) monotherapy and the combination of obinutuzumab plus chlorambucil (obi) are approved for previously untreated chronic lymphocytic leukemia (CLL). No trials directly comparing their efficacy are available. Therefore a matching-adjusted indirect comparison (MAIC) was perf...

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Autores principales: Van Sanden, Suzy, Baculea, Simona, Diels, Joris, Cote, Sarah
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504213/
https://www.ncbi.nlm.nih.gov/pubmed/28573505
http://dx.doi.org/10.1007/s12325-017-0564-1
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author Van Sanden, Suzy
Baculea, Simona
Diels, Joris
Cote, Sarah
author_facet Van Sanden, Suzy
Baculea, Simona
Diels, Joris
Cote, Sarah
author_sort Van Sanden, Suzy
collection PubMed
description INTRODUCTION: Ibrutinib (ibr) monotherapy and the combination of obinutuzumab plus chlorambucil (obi) are approved for previously untreated chronic lymphocytic leukemia (CLL). No trials directly comparing their efficacy are available. Therefore a matching-adjusted indirect comparison (MAIC) was performed to provide insight into their relative efficacy in terms of progression-free survival (PFS) and overall survival (OS). MAIC attempts to adjust for between-trial differences in factors known or suspected to influence treatment effects, to minimize bias. METHODS: A MAIC within a Bayesian framework was conducted using individual patient data from the RESONATE-2 study of ibr versus chlorambucil and published data from the CLL11 study of obi versus chlorambucil. Both studies were conducted in patients ineligible for full-dose fludarabine-based therapy. After matching, the reweighted adjusted relative efficacy measure of ibr versus chlorambucil from RESONATE-2 [hazard ratio (HR), 95% credible interval (CrI)] was compared with that of obi versus chlorambucil from CLL11 for each endpoint, using a Bayesian indirect comparison. RESULTS: Our results suggest that in a population with similar average baseline characteristics to CLL11, ibr would improve PFS and OS outcomes compared to obi. Before matching, the HRs for ibr versus obi were 0.48 [CrI = 0.22–1.02, p(HR <1) = 97%], 0.85 [CrI = 0.44–1.63, p(HR <1) = 69%], and 0.40 [CrI = 0.10–1.54, p(HR <1) = 91%] for PFS by investigator assessment, PFS by independent review committee, and OS, respectively. After matching on all available characteristics the HRs decreased to 0.12 [CrI = 0.02–0.97, p(HR <1) = 98%], 0.24 [CrI = 0.04–1.35, p(HR <1) = 95%], and 0.21 [CrI = <0.01–8.89, p(HR <1) = 79%], respectively. There was a large variance around the treatment effect for OS due to the low number of deaths. CONCLUSION: Our analysis suggests that ibrutinib is highly likely to provide greater PFS benefit than obinutuzumab plus chlorambucil in older or less fit patients with previously untreated CLL. There is also an indication of improvement in OS, albeit with a higher uncertainty due to the low number of events. FUNDING: Janssen-Cilag Ltd. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12325-017-0564-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-55042132017-07-25 Comparative Efficacy of Ibrutinib Versus Obinutuzumab + Chlorambucil in First-Line Treatment of Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison Van Sanden, Suzy Baculea, Simona Diels, Joris Cote, Sarah Adv Ther Original Research INTRODUCTION: Ibrutinib (ibr) monotherapy and the combination of obinutuzumab plus chlorambucil (obi) are approved for previously untreated chronic lymphocytic leukemia (CLL). No trials directly comparing their efficacy are available. Therefore a matching-adjusted indirect comparison (MAIC) was performed to provide insight into their relative efficacy in terms of progression-free survival (PFS) and overall survival (OS). MAIC attempts to adjust for between-trial differences in factors known or suspected to influence treatment effects, to minimize bias. METHODS: A MAIC within a Bayesian framework was conducted using individual patient data from the RESONATE-2 study of ibr versus chlorambucil and published data from the CLL11 study of obi versus chlorambucil. Both studies were conducted in patients ineligible for full-dose fludarabine-based therapy. After matching, the reweighted adjusted relative efficacy measure of ibr versus chlorambucil from RESONATE-2 [hazard ratio (HR), 95% credible interval (CrI)] was compared with that of obi versus chlorambucil from CLL11 for each endpoint, using a Bayesian indirect comparison. RESULTS: Our results suggest that in a population with similar average baseline characteristics to CLL11, ibr would improve PFS and OS outcomes compared to obi. Before matching, the HRs for ibr versus obi were 0.48 [CrI = 0.22–1.02, p(HR <1) = 97%], 0.85 [CrI = 0.44–1.63, p(HR <1) = 69%], and 0.40 [CrI = 0.10–1.54, p(HR <1) = 91%] for PFS by investigator assessment, PFS by independent review committee, and OS, respectively. After matching on all available characteristics the HRs decreased to 0.12 [CrI = 0.02–0.97, p(HR <1) = 98%], 0.24 [CrI = 0.04–1.35, p(HR <1) = 95%], and 0.21 [CrI = <0.01–8.89, p(HR <1) = 79%], respectively. There was a large variance around the treatment effect for OS due to the low number of deaths. CONCLUSION: Our analysis suggests that ibrutinib is highly likely to provide greater PFS benefit than obinutuzumab plus chlorambucil in older or less fit patients with previously untreated CLL. There is also an indication of improvement in OS, albeit with a higher uncertainty due to the low number of events. FUNDING: Janssen-Cilag Ltd. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12325-017-0564-1) contains supplementary material, which is available to authorized users. Springer Healthcare 2017-06-01 2017 /pmc/articles/PMC5504213/ /pubmed/28573505 http://dx.doi.org/10.1007/s12325-017-0564-1 Text en © The Author(s) 2017 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Van Sanden, Suzy
Baculea, Simona
Diels, Joris
Cote, Sarah
Comparative Efficacy of Ibrutinib Versus Obinutuzumab + Chlorambucil in First-Line Treatment of Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison
title Comparative Efficacy of Ibrutinib Versus Obinutuzumab + Chlorambucil in First-Line Treatment of Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison
title_full Comparative Efficacy of Ibrutinib Versus Obinutuzumab + Chlorambucil in First-Line Treatment of Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison
title_fullStr Comparative Efficacy of Ibrutinib Versus Obinutuzumab + Chlorambucil in First-Line Treatment of Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison
title_full_unstemmed Comparative Efficacy of Ibrutinib Versus Obinutuzumab + Chlorambucil in First-Line Treatment of Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison
title_short Comparative Efficacy of Ibrutinib Versus Obinutuzumab + Chlorambucil in First-Line Treatment of Chronic Lymphocytic Leukemia: A Matching-Adjusted Indirect Comparison
title_sort comparative efficacy of ibrutinib versus obinutuzumab + chlorambucil in first-line treatment of chronic lymphocytic leukemia: a matching-adjusted indirect comparison
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5504213/
https://www.ncbi.nlm.nih.gov/pubmed/28573505
http://dx.doi.org/10.1007/s12325-017-0564-1
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