Rucaparib for maintenance treatment of platinum-sensitive, recurrent ovarian carcinoma: Final results of the phase 3, randomized, placebo-controlled ARIEL3 trial Journal Article
| Authors: | Ledermann, J. A.; Oza, A. M.; Lorusso, D.; Aghajanian, C.; Oaknin, A.; Dean, A.; Colombo, N.; Weberpals, J. I.; Clamp, A. R.; Scambia, G.; Leary, A.; Holloway, R. W.; Gancedo, M. A.; Fong, P. C.; Goh, J. C.; O'Malley, D. M.; Armstrong, D. K.; Banerjee, S.; García-Donas, J.; Swisher, E. M.; Lebreton, C.; Konecny, G. E.; McNeish, I. A.; Scott, C. L.; Maloney, L.; Goble, S.; Lin, K. K.; Coleman, R. L. |
| Article Title: | Rucaparib for maintenance treatment of platinum-sensitive, recurrent ovarian carcinoma: Final results of the phase 3, randomized, placebo-controlled ARIEL3 trial |
| Abstract: | Background: In ARIEL3, rucaparib maintenance significantly improved progression-free survival (PFS; primary endpoint) and long-term follow-up (LTFU) outcomes (including PFS2: time to disease progression on subsequent therapy or death) versus placebo in patients with recurrent, platinum-sensitive ovarian cancer. Here we report the final analysis of overall survival (OS; key secondary endpoint), LTFU outcomes, and safety. Methods: OS and updated LTFU efficacy outcomes were analyzed (data cutoff date: April 4, 2022) across three nested populations (BRCA-mutated, homologous recombination deficient [HRD], and intention to treat [ITT]). Results: Patients were randomized 2:1 to rucaparib (600 mg BID; n = 375) or placebo (n = 189). Median follow-up was 77.0 months. 168 patients in the placebo arm received subsequent treatment; of these, 77 (46 %) received a poly(ADP-ribose) polymerase inhibitor–containing treatment. Median OS from randomization post chemotherapy for rucaparib vs placebo was 45.9 vs 47.8 months (HR 0.83, 95 % CI 0.58–1.19) for the BRCA-mutated population; no OS benefit was found with rucaparib in the HRD and ITT populations. Median PFS2 for rucaparib vs placebo was 26.1 vs 18.4 months (HR 0.67, 95 % CI 0.48–0.94) for the BRCA-mutated population. Rucaparib numerically improved PFS2 and other LTFU outcomes versus placebo in the HRD and ITT populations. Safety was consistent with prior reports; myelodysplastic syndrome and/or acute myeloid leukemia occurred in 4 % and 3 % of patients in the rucaparib and placebo arms, respectively. Conclusions: OS was similar between treatment arms. PFS benefit with rucaparib was maintained through the subsequent therapy line. These data support rucaparib as maintenance treatment for recurrent ovarian carcinoma. © 2025 |
| Keywords: | adult; cancer survival; controlled study; aged; aged, 80 and over; middle aged; major clinical study; overall survival; genetics; clinical trial; fatigue; mortality; cancer recurrence; placebo; drug safety; follow up; ovarian neoplasms; homologous recombination; progression free survival; multiple cycle treatment; neoplasm recurrence, local; anemia; nausea; randomized controlled trial; maintenance therapy; pathology; asthenia; myelodysplastic syndrome; multicenter study; tumor recurrence; ovary tumor; ovary carcinoma; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; phase 3 clinical trial; drug therapy; indoles; double blind procedure; double-blind method; indole derivative; brca; long-term follow-up; progression-free survival; recurrent ovarian cancer; clinical outcome; acute myeloid leukemia; maintenance chemotherapy; rucaparib; very elderly; intention to treat analysis; humans; human; female; article; poly(adp-ribose) polymerase inhibitor; poly(adp-ribose) polymerase inhibitors; carcinoma, ovarian epithelial; homologous recombination deficient; pfs2; progression-free interval |
| Journal Title: | European Journal of Cancer |
| Volume: | 225 |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2025-07-25 |
| Start Page: | 115584 |
| Language: | English |
| DOI: | 10.1016/j.ejca.2025.115584 |
| PUBMED: | 40580808 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
