Population exposure-efficacy and exposure-safety analyses for rucaparib in patients with recurrent ovarian carcinoma from Study 10 and ARIEL2.
- Abstract:
- OBJECTIVE: To evaluate correlations between rucaparib exposure and selected efficacy and safety endpoints in patients with recurrent ovarian carcinoma using pooled data from Study 10 and ARIEL2. METHODS: Efficacy analyses were limited to patients with carcinomas harboring a deleterious BRCA1 or BRCA2 mutation who had received ≥2 prior lines of chemotherapy. Safety was evaluated in all patients who received ≥1 rucaparib dose. Steady-state daily area under the concentration-time curve (AUCss) and maximum concentration (Cmax,ss) for rucaparib were calculated for each patient and averaged by actual dose received over time (AUCavg,ss and Cmax,avg,ss) using a previously developed population pharmacokinetic model. RESULTS: Rucaparib exposure was dose-proportional and not associated with baseline patient weight. In the exposure-efficacy analyses (n = 121), AUCavg,ss was positively associated with independent radiology review-assessed RECIST response in the subgroup of patients with platinum-sensitive recurrent disease (n = 75, p = 0.017). In the exposure-safety analyses (n = 393, 40 mg once daily to 840 mg twice daily [BID] starting doses), most patients received a 600 mg BID rucaparib starting dose, with 27% and 21% receiving 1 or ≥2 dose reductions, respectively. Cmax,ss was significantly correlated with grade ≥2 serum creatinine increase, grade ≥3 alanine transaminase/aspartate transaminase increase, platelet decrease, fatigue/asthenia, and maximal hemoglobin decrease (p
- Authors:
- GE Konecny, AM Oza, AV Tinker, A Oaknin, R Shapira-Frommer, I Ray-Coquard, C Aghajanian, RL Coleman, DM O'Malley, A Leary, L-M Chen, D Provencher, L Ma, JD Brenton, C Castro, M Green, AD Simmons, J Beltman, T Harding, KK Lin, S Goble, L Maloney, RS Kristeleit, IA McNeish, EM Swisher, JJ Xiao
- Journal:
- Gynecol Oncol
- Citation info:
- 161(3):668-675
- Publication date:
- 1st Jun 2021
- Full text
- DOI