Amit Oza1, Stanley Kaye2, Jan Van Tornout3, Cristiana Sessa4, Martin Gore2, R Wendel Naumann5, Hal Hirte6, Nicoletta Colombo7, Jihong Chen3, Seema Gorla3, Srinivasu Poondru3, Margaret Singh3, Joyce Steinberg3, Geoff Yuen3, Susana Banerjee8. 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.
RCT Entities:
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.
Authors: Rachel N Grisham; Kathleen N Moore; Michael S Gordon; Wael Harb; Gwendolyn Cody; Darragh F Halpenny; Vicky Makker; Carol A Aghajanian Journal: Clin Cancer Res Date: 2018-05-29 Impact factor: 12.531
Authors: Jihao Xu; Wen-Hsin Chang; Lon Wolf R Fong; Robert H Weiss; Sung-Liang Yu; Ching-Hsien Chen Journal: Signal Transduct Target Ther Date: 2019-01-25