The oral PARP inhibitor rucaparib showed strong activity and an acceptable safety profile in women with high-grade, BRCA-mutated ovarian carcinoma who had previously received at least two lines of chemotherapy, according to a pooled analysis of early studies presented at the European Society of Medical Oncology (ESMO) 2016 Congress in Copenhagen.
Rucaparib’s manufacturer, Clovis Oncology, submitted a new drug application (NDA) to the US Food and Drug Administration (FDA) earlier this year, and the FDA granted the agent priority review in August. Rucaparib also received Breakthrough Designation from the agency in April 2015.
The data presented at the ESMO Congress included patients from two single-arm, open-label, phase II studies. In total, there were 106 patients analyzed for rucaparib’s efficacy, and 377 included in a safety analysis. The results were presented by Rebecca S. Kristeleit, MD, PhD, of the University College London; the dataset has been submitted to the FDA.
Among the 106 patients in the efficacy population, the objective response rate (ORR) was 54%. There were 9 complete responses and 48 partial responses, and another 36 patients (34%) had stable disease as their best response; 9 patients had progressive disease, and 4 were not evaluable.
ORR was also assessed according to various subgroups. Patients with BRCA1 and BRCA2 mutations both had ORRs of 54%; those with a germline BRCA mutation had a 53% response rate, compared with 46% in those with somatic mutations.
Most of the patients (61%) had received three or more prior therapies, and 39% had received two; the latter group achieved an ORR of 68%. Patients who had a progression-free interval (PFI) of less than 6 months (27 patients) had an ORR of only 19%, while those with a PFI of 6 to 12 months had an ORR of 63%, and those with a PFI above 12 months had an ORR of 74%. The median progression-free survival was 10 months in the efficacy population.
All patients experienced at least one treatment-emergent adverse event (AE), and 61% of the 377-patient safety population experienced at least one event of grade 3 or higher. Forty-seven percent of patients experienced at least one treatment-related AE of grade 3 or higher. AEs that led to dose interruption occurred in 59% of patients.
The most common AEs related to dose reduction included anemia (17%), asthenia/fatigue (14%), and nausea (11%). Treatment discontinuation was commonly related to asthenia/fatigue (2%), small intestinal obstruction (2%), and nausea (1%). There were nine deaths (2%) related to AEs; eight of those were due to disease progression, and one was due to sepsis, which was deemed unrelated to the study drug.
“These results demonstrate that rucaparib may represent an important option for women with multiply relapsed BRCA-mutated ovarian cancer based on its encouraging efficacy and tolerability,” Kristeleit said in a press release. “In my opinion, rucaparib has the hallmarks of an important new therapeutic option for ovarian cancer patients.”
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