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Gynecol Oncol. 2018 May;149(2):275-282. doi: 10.1016/j.ygyno.2018.01.019. Epub 2018 Feb 14.

Phase 2 study evaluating intermittent and continuous linsitinib and weekly paclitaxel in patients with recurrent platinum resistant ovarian epithelial cancer.

Author information

1
Princess Margaret Cancer Centre, University of Toronto, ON, Canada. Electronic address: Amit.oza@uhn.ca.
2
The Royal Marsden and The Institute of Cancer Research, London, UK.
3
Astellas Pharma Global Development, Northbrook, IL, USA.
4
Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
5
Levine Cancer Institute at Carolinas Healthcare System, Charlotte, NC, USA.
6
Juravinski Cancer Centre, Hamilton, ON, Canada.
7
European Institute of Oncology and University of Milan-Bicocca, Milan, Italy.
8
The Royal Marsden and The Institute of Cancer Research, London, UK. Electronic address: susana.banerjee@rmh.nhs.uk.

Abstract

BACKGROUND:

Linsitinib, an oral, dual inhibitor of insulin-like growth factor-1 receptor and insulin receptor, in combination with weekly paclitaxel, may improve clinical outcomes compared with paclitaxel alone in patients with refractory or platinum-resistant ovarian cancer.

PATIENTS AND METHODS:

This open-label phase 1/2 clinical trial (NCT00889382) randomized patients with refractory or platinum-resistant ovarian cancer (1:1:1) to receive either oral intermittent linsitinib (600mg once daily on Days 1-3 per week) combined with paclitaxel (80mg/m2 on Days 1, 8, and 15; Arm A) or continuous linsitinib (150mg twice daily) in combination with paclitaxel (Arm B), or paclitaxel alone (Arm C). Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety/tolerability.

RESULTS:

A total of 152 women were randomized to treatment (n=51 Arm A; n=51 Arm B, n=50 Arm C). In combination with paclitaxel, neither intermittent linsitinib (median PFS 2.8months; 95% confidence interval [CI]:2.5-4.4) nor continuous linsitinib (median PFS 4.2months; 95% CI:2.8-5.1) improved PFS over weekly paclitaxel alone (median PFS 5.6months; 95% CI:3.2-6.9). No improvement in ORR, DCR, or OS in either linsitinib dosing schedule was observed compared with paclitaxel alone. Adverse event (AE) rates, including all-grade and grade 3/4 treatment-related AEs, and treatment-related AEs leading to discontinuation, were higher among patients receiving intermittent linsitinib compared with the other treatment arms.

CONCLUSION:

Addition of intermittent or continuous linsitinib with paclitaxel did not improve outcomes in patients with platinum-resistant/refractory ovarian cancer compared with paclitaxel alone.

PMID:
29454514
DOI:
10.1016/j.ygyno.2018.01.019
[Indexed for MEDLINE]
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