Randomized, phase II, placebo-controlled, double-blind study with and without
enzastaurin in combination with paclitaxel and carboplatin as first-line
treatment followed by maintenance treatment in advanced ovarian cancer.
Author(s): Vergote IB(1), Chekerov R, Amant F, Harter P, Casado A, Emerich J, Bauknecht T,
Mansouri K, Myrand SP, Nguyen TS, Shi P, Sehouli J.
Affiliation(s): Author information:
(1)University Hospital, Leuven, Belgium. ignace.vergote@uzleuven.be
Publication date & source: 2013, J Clin Oncol. , 31(25):3127-32
PURPOSE: Enzastaurin is an oral serine/threonine kinase inhibitor antitumor
agent. Our phase II trial tested the efficacy and safety of enzastaurin added to
a standard carboplatin/paclitaxel chemotherapy regimen in patients with newly
diagnosed advanced ovarian cancer.
PATIENTS AND METHODS: This was a randomized, placebo-controlled study in patients
with International Federation of Gynecology and Obstetrics stage IIB to IV
ovarian, fallopian tube, or peritoneal epithelial carcinoma. Patients were
randomly assigned to six cycles of chemotherapy (paclitaxel/carboplatin ±
enzastaurin [PCE/PC]) followed by maintenance therapy (enzastaurin/placebo).
Primary end point was progression-free survival (PFS). Secondary measures
included response rate, safety assessment, and translational research.
RESULTS: A total of 142 patients were randomly assigned to PCE (n = 69) or PC (n
= 73). Patients in the PCE group had a 3.7-month longer median PFS compared with
patients in the PC group; this was not statistically significant (hazard ratio
[HR], 0.80; 95% CI, 0.50 to 1.29; P = .37). Safety profiles of the treatment arms
were comparable. Frequency of discontinuation because of adverse events was
similar (PCE, 11.9%; PC, 9.7%). Multivariate analyses confirmed the importance of
optimal debulking with regard to PFS (debulking optimal v suboptimal: HR, 0.51;
95% CI, 0.30 to 0.85; P = .009). HR for covariate stage (stage IIB to IIIB v IIIC
to IV) was not statistically significant (0.75; 95% CI, 0.38 to 1.47; P = .40).
Translational research of immunohistochemistry protein assays did not identify
any markers significantly associated with treatment difference regarding PFS.
CONCLUSION: The PCE combination increased PFS, but it was not significantly
superior to PC in this phase II study.
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