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

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. This open-label phase 1/2 clinical...

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Bibliographic Details
Published in:Gynecologic oncology 2018-05, Vol.149 (2), p.275-282
Main Authors: Oza, Amit, Kaye, Stanley, Van Tornout, Jan, Sessa, Cristiana, Gore, Martin, Naumann, R. Wendel, Hirte, Hal, Colombo, Nicoletta, Chen, Jihong, Gorla, Seema, Poondru, Srinivasu, Singh, Margaret, Steinberg, Joyce, Yuen, Geoff, Banerjee, Susana
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Carcinoma, Ovarian Epithelial
Drug Administration Schedule
Drug Resistance, Neoplasm
Female
Humans
Imidazoles - administration & dosage
Middle Aged
Neoplasm Recurrence, Local - drug therapy
Neoplasm Recurrence, Local - pathology
Neoplasms, Glandular and Epithelial - drug therapy
Neoplasms, Glandular and Epithelial - pathology
Organoplatinum Compounds - pharmacology
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - pathology
Paclitaxel - administration & dosage
Pyrazines - administration & dosage
Treatment Outcome
Young Adult
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Summary: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. 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. 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. Addition of intermittent or continuous linsitinib with paclitaxel did not improve outcomes in patients with platinum-resistant/refractory ovarian cancer compared with paclitaxel alone. •First randomized ovarian cancer trial targeting IGF1R pathway in combination with chemotherapy.•Linsitinib added to paclitaxel either as an intermittent or continuous schedule.•Addition of linsitinib did not improve outcomes in patients with ovarian cancer.
ISSN:0090-8258
1095-6859
DOI:10.1016/j.ygyno.2018.01.019