Safety and efficacy results from two randomized expansions of a phase I study of a tablet formulation of the PARP inhibitor, olaparib, in ovarian and breast cancer patients with BRCA1/2 mutations.

Abstract

3048 Background: We previously reported the comparative bioavailability of the capsule (CAP) formulation of olaparib and the more convenient new tablet (TAB) formulation (Molife et al ASCO 2010). We subsequently performed two separate dose expansions (DE1 and DE2) to explore comparative safety and efficacy of the TAB (NCT00777582). Methods: Patients with breast or ovarian cancer and BRCA1/2 mutations, ECOG PS 0–2 and adequate organ function were randomized to receive: DE1: 200 TAB or 400 CAP; DE2: 300 TAB, 400 TAB or 400 CAP (all mg BID). Endpoints included safety, pharmacokinetics and exploratory analysis of efficacy (change in tumor size at 8 weeks by RECIST 1.0). Groups were compared using analysis of covariance, including baseline tumor size and treatment as covariates; results are presented using least square (LS) means. Results: 24 patients (ovarian n=15, breast n=9) entered DE1 and 53 patients (ovarian n=38, breast n=15) entered DE2. Baseline characteristics including age, BRCA mutation status and tumor histology were balanced. The table shows key toxicity-related information and change in tumor size at 8 weeks by cohort. Conclusions: These data suggest a dose-response effect for tolerability and, possibly, efficacy with the new TAB between 200 and 400 mg BID. Further studies will require dosing according to patient tolerability within this dose range. [Table: see text]