Rucaparib significantly extends PFS in advanced, relapsed BRCA-mutated ovarian cancer
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Rucaparib significantly prolonged PFS compared with chemotherapy for women with BRCA-mutated advanced, relapsed ovarian cancer, according to a study presented at the virtual Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
The study also showed that presence of a BRCA reversion mutation implies relative resistance to rucaparib (Rubraca, Clovis Oncology), a poly(ADP-ribose) polymerase (PARP) inhibitor, Rebecca Kristeleit, BSc, MRCP, PhD, clinical senior lecturer and consultant medical oncologist at University College London and UCL Cancer Institute, told Healio.
“The take-home message from this trial is that rucaparib is confirmed as an effective, oral, nonchemotherapy treatment for [women with relapsed BRCA-mutated ovarian cancer] that can be used as an alternative to either platinum-based or nonplatinum chemotherapy,” she said. “It is an option for patients irrespective of their platinum status.”
Kristeleit and colleagues analyzed data from the randomized, open-label, international phase 3 ARIEL4 study, in which researchers evaluated the safety and efficacy of rucaparib vs. standard-of-care chemotherapy among 349 women (median age, 58 years; range, 38-85) with relapsed high-grade epithelial ovarian (94.8%), fallopian tube (2.9%) or primary peritoneal (2.3%) cancer who had a deleterious BRCA mutation and had received at least two prior chemotherapy regimens but no PARP inhibitors.
The investigators randomly assigned the women 2:1 to either oral rucaparib dosed at 600 mg twice daily (n = 233) or standard-of-care chemotherapy (n = 116). They stratified randomization based on platinum status. Women in the chemotherapy group with platinum-resistant (progression-free interval [PFI] of 1 to < 6 months) or partially platinum-sensitive (PFI of 6 to < 12 months) disease received weekly paclitaxel dosed at 60 mg/m2 to 80 mg/m2, whereas patients with fully platinum-sensitive (PFI 12 months) disease received researchers’ choice of single-agent platinum or doublet chemotherapy.
Overall, 179 women (51.3%) had platinum-resistant disease, 96 (27.5%) had partially platinum-sensitive disease and 74 (21.2%) had fully platinum-sensitive disease.
Investigator-assessed PFS served as the study’s primary endpoint. Secondary endpoints included objective response rate per RECIST version 1.1 and safety.
Researchers first evaluated each efficacy endpoint in the efficacy population, which excluded women with BRCA reversion mutations (n = 23) detected in plasma samples prior to study treatment, followed by the intent-to-treat population.
Results showed significantly longer median PFS with rucaparib vs. chemotherapy among both the efficacy population (7.4 months vs. 5.7 months; HR = 0.64; 95% CI, 0.49-0.84) and the intent-to-treat population (7.4 months vs. 5.7 months; HR = 0.67; 95% CI, 0.52-0.86).
However, an exploratory analysis of the 23 patients with BRCA reversion mutations (rucaparib, n = 13; chemotherapy, n = 10) showed shorter median PFS with rucaparib (2.9 months vs. 5.5 months; HR = 2.76, 95% CI, 0.98-7.75).
The efficacy and intent-to-treat populations had similar ORRs (rucaparib, 40.3% vs. 37.9%; chemotherapy, 32.3% vs. 30.2%) and the same median duration of response (rucaparib, 9.4 months; chemotherapy, 7.2 months).
Adverse events appeared consistent with the known safety profiles of rucaparib and chemotherapy and included anemia/decreased hemoglobin (53.9% vs. 31.9%; grade 3, 22.4% vs. 5.3%), nausea (53.4% vs. 31.9%; grade 3, 2.6% vs. 0%) and asthenia/fatigue (49.6% vs. 44.2%; grade 3, 8.2% vs. 2.7%). Adverse events that led to treatment discontinuation occurred among 19 patients (8.2%) in the rucaparib group and 14 patients (12.4%) in the chemotherapy group.
“Rucaparib can be used instead of chemotherapy for some [women with ovarian cancer], adding a further treatment choice to the pathway for these women,” Kristeleit said. “In addition, the association of a BRCA reversion mutation with worse outcome following rucaparib suggests we, as a community, should consider prospective testing for a BRCA reversion mutation among women planned for treatment with a PARP inhibitor.”
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Kristeleit RS, et al. Abstract 11479. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (virtual); March 19-25, 2021.
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