Pooled Analysis Supports Suggested Rucaparib Starting Dose in Recurrent Ovarian Cancer

In patients with recurrent ovarian carcinoma, pooled data from 2 clinical trials confirmed the safety of rucaparib at the recommended starting dose of 600 mg, with subsequent dose reductions following the occurrence of any treatment-emergent adverse events. These findings were presented in a poster by Gottfried E. Konecny, MD, lead clinician for gynecologic oncology in the Department of Medicine at the University of California at Los Angeles, at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.

The aim of this study was to evaluate the correlations between rucaparib pharmacokinetic exposure and safety/efficacy in patients with recurrent ovarian cancer, using data from Study 10 (a study of oral rucaparib in patients with a solid tumor or with germline BRCA-mutated ovarian cancer) and ARIEL2 (a study of rucaparib in patients with platinum-sensitive, relapsed, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer).

Patients received escalating doses of rucaparib in phase 1, followed by the recommended starting dose of 600 mg rucaparib twice a day in phase 2. According to the study authors, a published population pharmacokinetic model was used to estimate the actual dose-normalized average steady-state area under the plasma drug concentration-time curve (AUCss) and Cmax.

AUC and Cmax are pharmacokinetic measures that determine the level of exposure to a drug, and the researchers sought to evaluate the side effects associated with exposure to rucaparib. AUC is a method of measuring absorption of a drug, and Cmax is the highest concentration of a drug in the blood, cerebrospinal fluid, or target organ after a dose is given.

Safety was evaluated in patients who received at least one rucaparib dose, and efficacy was assessed in patients who had a deleterious BRCA mutation or had tumors with high genomic loss of heterozygosity.

In this analysis, rucaparib pharmacokinetic exposure was dose-proportional and was not associated with baseline patient weight or baseline platelet counts.

In the exposure-safety analysis of 375 patients, most patients received a starting dose of 600 mg twice daily, with 27% and 21% of patients receiving 1 or ≥2 dose reductions, respectively. “Rucaparib was well tolerated overall,” Dr Konecny reported. Cmax was significantly correlated with grade ≥2 serum creatinine increase and grade ≥3 increases in liver enzymes (ALT/AST), platelet decrease, fatigue/asthenia, and maximal hemoglobin decrease.

In the exposure-efficacy analysis of 102 patients with BRCA mutations, AUCss was positively associated with an independent radiologist reviewer–assessed objective response rate in 75 patients with platinum-sensitive disease, but not in the 27 patients with platinum-resistant recurrent ovarian cancer who had received ≥2 prior lines of chemotherapy, the investigators reported.

Based on these data, Dr Konecny and colleagues maintain that “high Cmax was associated with more frequent clinical safety events, but was not associated with low patient weight or baseline platelet counts. Additionally, higher rucaparib AUCss was associated with improved independent radiologist reviewer–assessed response in platinum-sensitive, BRCA-mutated recurrent ovarian cancer.”


  • SGO 2020 Annual Meeting on Women’s Cancer. Abstract 190.

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