Converging or Crossing Curves: Untie the Gordian Knot or Cut it Appropriate Statistics for Non-Proportional Hazards in Decitabine DACO-016 Study AMLReportar como inadecuado




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Advances in Therapy

, Volume 32, Issue 9, pp 854–862

First Online: 14 September 2015Received: 20 July 2015DOI: 10.1007-s12325-015-0238-9

Cite this article as: Tomeczkowski, J., Lange, A., Güntert, A. et al. Adv Ther 2015 32: 854. doi:10.1007-s12325-015-0238-9

Abstract

IntroductionAmong patients with acute myeloid leukemia AML, the DACO-016 randomized study showed reduction in mortality for decitabine Dacogen DAC, Eisai Inc., Woodcliff Lake, NJ, USA compared with treatment choice TC: at primary analysis the hazard ratio HR was 0.85 95% confidence interval 0.69–1.04; stratified log-rank P = 0.108. With two interim analyses, two-sided alpha was adjusted to 0.0462. With 1-year additional follow-up the HR reached 0.82 nominal P = 0.0373. These data resulted in approval of DAC in the European Union, though not in the United States. Though pre-specified, the log-rank test could be considered not optimal to assess the observed survival difference because of the non-proportional hazard nature of the survival curves.

MethodsWe applied the Wilcoxon test as a sensitivity analysis. Patients were randomized to DAC N = 242 or TC N = 243. One-hundred and eight 44.4% patients in the TC arm and 91 37.6% patients in the DAC arm selectively crossed over to subsequent disease modifying therapies at progression, which might impact the survival beyond the median with resultant converging curves and disproportional hazards.

ResultsThe stratified Wilcoxon test showed a significant improvement in median CI 95% overall survival with DAC 7.7 6.2; 9.2 months versus TC 5.0 4.3; 6.3 months; P = 0.0458.

ConclusionWilcoxon test indicated significant increase in survival for DAC versus TC compared to log-rank test.

FundingJanssen-Cilag GmbH.

KeywordsAcute myeloid leukemia Dacogen Decitabine Non-proportional hazards Log-rank test Oncology Wilcoxon test Electronic supplementary materialThe online version of this article doi:10.1007-s12325-015-0238-9 contains supplementary material, which is available to authorized users.

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Autor: Jörg Tomeczkowski - Ansgar Lange - Andreas Güntert - Pushpike Thilakarathne - Joris Diels - Liang Xiu - Peter De Porre -

Fuente: https://link.springer.com/







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