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Survival adjusting for crossover: phase 3 study of ibrutinib vs. chlorambucil in older patients with untreated chronic lymphocytic leukemia/small lymphocytic lymphoma.

ABSTRACT:

SUBMITTER: Coutre S

PROVIDER: S-EPMC6058772 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Survival adjusting for crossover: phase 3 study of ibrutinib <i>vs</i>. chlorambucil in older patients with untreated chronic lymphocytic leukemia/small lymphocytic lymphoma.

Coutre Steven S Tedeschi Alessandra A Robak Tadeusz T Barr Paul M PM Owen Carolyn C Bairey Osnat O Burger Jan J Zhou Cathy C Styles Lori L James Danelle F DF Kipps Thomas J TJ

Haematologica 20171123 6

PMID: 29170253

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Project description:IntroductionIbrutinib (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.MethodsA 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.ResultsOur 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.ConclusionOur 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.FundingJanssen-Cilag Ltd.

Dataset Information

Survival adjusting for crossover: phase 3 study of ibrutinib vs. chlorambucil in older patients with untreated chronic lymphocytic leukemia/small lymphocytic lymphoma.

Publications

Survival adjusting for crossover: phase 3 study of ibrutinib <i>vs</i>. chlorambucil in older patients with untreated chronic lymphocytic leukemia/small lymphocytic lymphoma.

Similar Datasets

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