Highlights
- •Pazopanib maintenance therapy extended PFS in patients with AEOC.
- •HR estimates for PFS by investigator were consistent with those of central review.
- •There was no evidence of investigator bias in estimates of disease progression.
Abstract
Background
Analysis of progression-free survival (PFS) as the primary endpoint in advanced epithelial
ovarian, fallopian tube, and primary peritoneal cancer (AEOC) trials may be confounded
by the difficulty of radiologic evaluation of disease progression and the potential
for discrepancy between investigator and blinded independent central assessments.
PFS as assessed by local investigator (INV) was the primary endpoint of AGO-OVAR16,
a randomized, double-blind trial of pazopanib maintenance therapy in AEOC. To confirm
the robustness of the primary analysis, PFS was also evaluated by blinded independent
central review (BICR).
Methods
Patients with histologically confirmed AEOC (N = 940) were randomized 1:1 to receive pazopanib 800 mg/day or placebo for up to 24 months. Tumor response in the intent-to-treat population was evaluated by CT/MRI every
6 months and analyzed per RECIST 1.0.
Results
Pazopanib prolonged PFS versus placebo by INV (median 17.9 vs 12.3 months; hazard ratio [HR] = 0.766, 95% confidence interval [CI]: 0.643–0.911; P = 0.0021). Results for PFS by BICR were similar (median 15.4 vs 11.8 months; HR = 0.802, 95% CI: 0.678–0.949; P = 0.0084). Progression events were recorded later by INV in 23% of pazopanib-treated
patients and 17% of placebo-treated patients. The overall concordance between INV
and BICR assessments was 84% and 86% in the pazopanib and placebo arms, respectively.
Conclusions
By INV and BICR assessments, maintenance therapy with pazopanib in AEOC provided a
significantly longer PFS than placebo. The good overall concordance between INV and
BICR assessments, as well as HR and P value consistency, supports the reliability of investigator-assessed PFS as the primary
endpoint in AGO-OVAR16.
Keywords
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Article info
Publication history
Published online: November 27, 2014
Accepted:
November 21,
2014
Received:
October 20,
2014
Footnotes
☆Clinical Trials Registration Number: NCT00866697 [http://clinicaltrials.gov/ct2/show/NCT00866697].
☆☆Previous Publication: Portions of the data were presented by Floquet A, et al. (oral presentation) at ESGO 2013; the abstract appeared in Int J Gynecol Cancer 2013;23(8 suppl 1):182–3.
Identification
Copyright
© 2014 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
