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

Matulonis, UA; Harter, P; Gourley, C; Friedlander, M; Vergote, I; Rustin, G; Scott, C; Meier, W; Shapira-Frommer, R; Safra, T; Matei, D; Fielding, A; Spencer, S; Parry, D; Grinsted, L; Ledermann, JA

Author(s): Matulonis, UA; Harter, P; Gourley, C; Friedlander, M; Vergote, I; Rustin, G; Scott, C; Meier, W; Shapira-Frommer, R; Safra, T; Matei, D; Fielding, A; Spencer, S; Parry, D; Grinsted, L; Ledermann, JA;
Details: Publication Year 2016-06-15,Volume 122,Issue #12,Page 1844-52
Journal Title: Cancer
Publication Type: Journal Article
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. (c) 2016 American Cancer Society.
Publisher: Wiley
Research Division(s): Stem Cells And Cancer
PubMed ID: 27062051
Publisher's Version: https://doi.org/10.1002/cncr.29995
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2017-05-26 02:39:21

Last Modified: 2017-05-26 03:02:17