1. Phase 2 study evaluating intermittent and continuous linsitinib and weekly paclitaxel in patients with recurrent platinum resistant ovarian epithelial cancer
- Author
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R. Wendel Naumann, Martin Gore, Susana Banerjee, Stanley B. Kaye, Margaret Singh, Seema Gorla, Cristiana Sessa, Jihong Chen, Joyce Steinberg, Geoff Yuen, Amit M. Oza, Nicoletta Colombo, Hal W. Hirte, Jan M. Van Tornout, Srinivasu Poondru, Oza, A, Kaye, S, Van Tornout, J, Sessa, C, Gore, M, Naumann, R, Hirte, H, Colombo, N, Chen, J, Gorla, S, Poondru, S, Singh, M, Steinberg, J, Yuen, G, and Banerjee, S
- Subjects
0301 basic medicine ,Oncology ,Adult ,Linsitinib ,medicine.medical_specialty ,Adolescent ,Organoplatinum Compounds ,Paclitaxel ,Phases of clinical research ,Carcinoma, Ovarian Epithelial ,Drug Administration Schedule ,03 medical and health sciences ,chemistry.chemical_compound ,Young Adult ,0302 clinical medicine ,Refractory ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Clinical endpoint ,Humans ,Neoplasms, Glandular and Epithelial ,Adverse effect ,Aged ,Ovarian Neoplasms ,business.industry ,Imidazoles ,Obstetrics and Gynecology ,Middle Aged ,medicine.disease ,030104 developmental biology ,Treatment Outcome ,chemistry ,Tolerability ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Pyrazines ,Female ,Neoplasm Recurrence, Local ,Ovarian cancer ,business - 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/m 2 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.
- Published
- 2017