PFS Improved With Maintenance Rucaparib in Recurrent Ovarian Cancer Irrespective of Prior Chemo

Domenica Lorusso, MD

In patients with platinum-sensitive recurrent ovarian cancer, the PARP inhibitor rucaparib (Rubraca) as maintenance treatment improved progression-free survival (PFS) versus placebo, despite the number of chemotherapy regimens. These data were part of a subgroup analysis of the phase III ARIEL3 study, which were presented at the 2018 ESMO Congress.¹

Results showed that patients in ARIEL3 who received either 2 or ≥3 prior lines of chemotherapy had an improvement in PFS. This finding was consistent across the intent-to-treat (ITT) population, those with BRCA-mutant tumors, and the “BRCA-like” population, which consists of BRCA wild-type/high loss of heterozygosity (LOH), reported Domenica Lorusso, MD, of the Fondazione IRCCS Instituto Nazionale de Tumori and MITO, Milan, Italy, during the meeting.

The double-blind, placebo-controlled, ARIEL3 trial enrolled 564 patients across 11 countries with platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma who had received at least 2 previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a performance status of 0 or 1, and had adequate organ function.

They were randomized 2:1 to receive oral rucaparib at 600 mg twice daily (n = 375) or placebo (n = 189) in 28-day cycles. The primary outcome was investigator-assessed PFS evaluated with use of an ordered step-down procedure for 3 nested cohorts: patients with BRCA mutations, patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high LOH), and the ITT population, assessed at screening and every 12 weeks thereafter. Across all primary subgroups, rucaparib significantly improved PFS.²

Rucaparib significantly improved PFS compared with placebo in all patient populations regardless of biomarker status. For those patients with BRCA-mutant tumors who received 2 lines of prior chemotherapy, median PFS was improved in the rucaparib maintenance group relative to placebo both by investigator assessment (21.9 vs 5.4 months; HR, 0.24) and by blinded independent central review (BICR; 26.8 vs 5.5 months; HR, 0.24).

Among the patients with BRCA-mutant tumors who received ≥3 lines of prior chemotherapy, median PFS was improved in the rucaparib arm relative to placebo both by investigator assessment (13.7 vs 5.4 months; HR, 0.21) and by BICR (18.0 vs 5.4 months; HR, 0.17).

In those with BRCA-mutant plus BRCA wild-type/high LOH tumors who received 2 prior lines of chemotherapy, median PFS by investigator assessment was 14.1 months in the rucaparib arm versus 5.5 months in the placebo arm (HR, 0.34); by BICR, it was 26.8 months versus 5.5 months, respectively (HR, 0.33).

For patients with BRCA-mutant plus BRCA wild-type/high LOH tumors who received ≥3 prior lines of chemotherapy, median PFS by investigator assessment was 11.1 months in the rucaparib maintenance arm versus 5.4 months in the placebo arm (HR, 0.27) and by BICR, it was 13.6 months versus 5.4 months, respectively (HR, 0.330).

In the ITT population, among those who received 2 prior lines of chemotherapy, median PFS improved from 5.4 months in the placebo group to 10.4 months in the rucaparib group (HR, 0.42) by investigator assessment and from 5.4 months to 17.1 months (HR, 0.37) by BICR.

Also in the ITT population that received ≥3 lines of prior chemotherapy, median PFS improved from 5.3 months in the placebo arm to 11.1 months in the rucaparib arm (HR, 0.28) by investigator assessment and from 5.3 months to 13.3 months (HR, 0.36) by BICR.

A greater proportion of rucaparib-treated patients versus those on placebo were progression free at 18 and 24 months, regardless of the number of lines of prior chemotherapy. By investigator assessment, the percentage of those in the ITT population who were progression free at 18 months was 33.3% on rucaparib and 6.7% on placebo arm among the group receiving 2 prior lines of chemotherapy, and 29.8% and 3.7%, respectively, among those receiving ≥3 lines of prior chemotherapy.

At 24 months, these percentages were 26.9% and 3.0%, respectively, and 23.2% and 3.7% respectively. These rates were somewhat higher by BICR, with about the same relative difference between the placebo and rucaparib arms.

Among patients with measurable disease at baseline, the objective response rate in rucaparib-treated patients was 16.3% among those who received 2 prior lines of chemotherapy and 21.8% among those who ≥3 lines of prior chemotherapy.

The safety profile of rucaparib in patients treated with either 2 or ≥3 lines of prior chemotherapy was consistent with that of the ITT population from prior reports. The most common grade ≥3 treatment-emergent adverse events in patients who received 2 or ≥3 lines of prior chemotherapy was anemia (24.5% and 16.1%), respectively.

References

1. Lorusso D, Coleman RL, Oza AM, et al. Subgroup analysis of rucaparib in platinum-sensitive recurrent ovarian carcinoma: effect of prior chemotherapy regimens in ARIEL3. In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract 947P.
2. Coleman RL, Oza AM, Lorusso D, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomized, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:1949-1961. doi: 10.1016/S0140-6736(17)32440-6.