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Blogger's note: search this blog using term: olaparib (numerous postings)
Abstract:
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
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.
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