Oza A, et al. - This study was designed to test the assumption that 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. Compared with paclitaxel alone, addition of intermittent or continuous linsitinib with paclitaxel did not improve outcomes.

Methods

• In this open-label phase 1/2 clinical trial, patients with refractory or platinum-resistant ovarian cancer were randomized (1:1:1) to receive either oral intermittent linsitinib (600 mg once daily on Days 1–3 per week) combined with paclitaxel (80 mg/m²on Days 1, 8, and 15; Arm A) or continuous linsitinib (150 mg twice daily) in combination with paclitaxel (Arm B), or paclitaxel alone (Arm C).
• Progression-free survival (PFS) was the primary endpoint.
• Overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety/tolerability were secondary endpoints.

Results

• Data showed that a total of 152 women were randomized to treatment (n = 51 Arm A; n = 51 Arm B, n = 50 Arm C).
• Researchers found that in combination with paclitaxel, neither intermittent linsitinib (median PFS 2.8 months; 95% confidence interval [CI]:2.5–4.4) nor continuous linsitinib (median PFS 4.2 months; 95% CI:2.8–5.1) improved PFS over weekly paclitaxel alone (median PFS 5.6 months; 95% CI:3.2–6.9).
• They also noted that in comparison with paclitaxel alone, there was no improvement in ORR, DCR, or OS in either linsitinib dosing schedule.
• Additionally, findings demonstrated that compared with the other treatment arms, patients receiving intermittent linsitinib had higher adverse event (AE) rates, including all-grade and grade 3/4 treatment-related AEs, and treatment-related AEs leading to discontinuation.