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Olaparib maintenance therapy in patients with platinum‐sensitive, relapsed serous ovarian cancer and a BRCA mutation: Overall survival adjusted for postprogression poly(adenosine diphosphate ribose) polymerase inhibitor therapy

Olaparib maintenance therapy in patients with platinum‐sensitive, relapsed serous ovarian cancer... BACKGROUND Maintenance treatment with the oral poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor olaparib (Lynparza) in Study 19 (study number, D0810C00019; ClinicalTrials.gov identifier, NCT00753545) significantly improved progression‐free survival in comparison with a placebo for patients with platinum‐sensitive, relapsed serous ovarian cancer with a BRCA1/2 mutation (BRCAm), but an interim analysis revealed no statistically significant overall survival (OS) benefit. However, 23% of the patients receiving the placebo switched to a PARP inhibitor after progression. To investigate whether this had a confounding effect on OS, this article reports an exploratory post hoc analysis that excluded all patients from sites where 1 or more placebo patients received postprogression PARP inhibitor treatment. METHODS In Study 19, 136 of the 265 patients receiving olaparib or a placebo had a BRCAm. Sixteen patients treated at 11 of the 82 investigational sites received a PARP inhibitor after progression; these sites were excluded from this analysis, and 97 BRCAm patients at 50 sites were included. OS was assessed with a Cox proportional hazards model analogous to the primary study analysis. A supporting rank‐preserving structural failure time (RPSFT) model analysis was undertaken for all 136 BRCAm patients. RESULTS The OS hazard ratio (HR) was 0.52 (95% confidence interval (CI), 0.28‐0.97) for the 97 BRCAm patients, whereas for the interim OS analysis with all 136 BRCAm patients, it was 0.73 (95% CI, 0.45‐1.17). The supportive RPSFT analysis HR was approximately 0.66. CONCLUSIONS The numerical improvement in the OS HR suggests that in Study 19, postprogression PARP inhibitor treatment had a confounding influence on the interim OS analysis for BRCAm patients. There is a degree of uncertainty due to the small sample size and the lack of data maturity. Cancer 2016;122:1844–52. © 2016 American Cancer Society. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Wiley

Olaparib maintenance therapy in patients with platinum‐sensitive, relapsed serous ovarian cancer and a BRCA mutation: Overall survival adjusted for postprogression poly(adenosine diphosphate ribose) polymerase inhibitor therapy

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References (17)

Publisher
Wiley
Copyright
"© 2016 American Cancer Society"
ISSN
0008-543X
eISSN
1097-0142
DOI
10.1002/cncr.29995
pmid
27062051
Publisher site
See Article on Publisher Site

Abstract

BACKGROUND Maintenance treatment with the oral poly(adenosine diphosphate ribose) polymerase (PARP) inhibitor olaparib (Lynparza) in Study 19 (study number, D0810C00019; ClinicalTrials.gov identifier, NCT00753545) significantly improved progression‐free survival in comparison with a placebo for patients with platinum‐sensitive, relapsed serous ovarian cancer with a BRCA1/2 mutation (BRCAm), but an interim analysis revealed no statistically significant overall survival (OS) benefit. However, 23% of the patients receiving the placebo switched to a PARP inhibitor after progression. To investigate whether this had a confounding effect on OS, this article reports an exploratory post hoc analysis that excluded all patients from sites where 1 or more placebo patients received postprogression PARP inhibitor treatment. METHODS In Study 19, 136 of the 265 patients receiving olaparib or a placebo had a BRCAm. Sixteen patients treated at 11 of the 82 investigational sites received a PARP inhibitor after progression; these sites were excluded from this analysis, and 97 BRCAm patients at 50 sites were included. OS was assessed with a Cox proportional hazards model analogous to the primary study analysis. A supporting rank‐preserving structural failure time (RPSFT) model analysis was undertaken for all 136 BRCAm patients. RESULTS The OS hazard ratio (HR) was 0.52 (95% confidence interval (CI), 0.28‐0.97) for the 97 BRCAm patients, whereas for the interim OS analysis with all 136 BRCAm patients, it was 0.73 (95% CI, 0.45‐1.17). The supportive RPSFT analysis HR was approximately 0.66. CONCLUSIONS The numerical improvement in the OS HR suggests that in Study 19, postprogression PARP inhibitor treatment had a confounding influence on the interim OS analysis for BRCAm patients. There is a degree of uncertainty due to the small sample size and the lack of data maturity. Cancer 2016;122:1844–52. © 2016 American Cancer Society.

Journal

CancerWiley

Published: Mar 15, 2017

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