In a recent clinical trial, researchers from Princess Margaret Cancer Centre (PM) investigated the drug rucarparib in comparison to standard chemotherapy for treating patients with relapsed ovarian cancer caused by BRCA gene mutations.
Most patients with advanced high-grade ovarian cancer respond to initial treatment but eventually relapse. This recurrent disease is generally incurable. Rucaparib has demonstrated efficacy in patients with a specific type of recurrent ovarian cancer. It inhibits poly(ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair.
To expand on previous evidence, including phase II clinical trials, Dr. Amit Oza’s group at PM led a randomized, controlled phase III trial, called ARIEL4. ARIEL4 compared rucaparib with the current standard-of-care chemotherapy in patients with relapsed ovarian cancer with BRCA mutations.
The trial involved 349 women from 12 countries who had previously undergone at least two chemotherapy treatments. They were randomly assigned to receive either rucaparib, taken as a daily pill, or chemotherapy. This cohort differed from previous studies because it included individuals with varying sensitivity to platinum-based chemotherapy, the standard first-line treatment for ovarian cancer.
The final report of this clinical trial examined overall survival, defined as the duration a patient lives following treatment. Overall survival was longer in patients assigned to chemotherapy (25.4 months) than those assigned to rucaparib (19.4 months). The research team suggested this could be attributed to one chemotherapy subgroup exhibiting greater resistance to treatment. In addition, no new or unexpected side effects were found in patients taking rucaparib.
However, the study did find that progression-free survival—the amount of time it takes for the disease to progress or get worse —was significantly longer with rucaparib than chemotherapy. These results were reported in a previous publication for the ARIEL4 study. Although the study was not designed to identify statistical differences between chemotherapy subgroups, this report found that patients in the rucaparib group had similar or longer progression-free survival versus patients in the chemotherapy group across all subgroups.
Researchers emphasize the need for further studies to optimize the use of PARP inhibitors, such as rucaparib, in combination with chemotherapy for advanced ovarian cancer treatment. Understanding the optimal treatment strategy could significantly impact patient outcomes.
The senior author of this study is Dr. Amit Oza, Senior Scientist at Princess Margaret Cancer Centre and Professor of Medicine at the University of Toronto.
This work was supported by Clovis Oncology and The Princess Margaret Cancer Foundation.
Dr. Amit Oza reports institutional research grants from AstraZeneca; has served on an advisory board (uncompensated) for GlaxoSmithKline; has served on advisory boards and steering committees (uncompensated) for Clovis Oncology and AstraZeneca; and as a principal investigator on investigator-initiated trials for Clovis Oncology, AstraZeneca, and GlaxoSmithKline.
For a full list of competing interests, see the manuscript.
Oza AM, Lisyanskaya A, Fedenko A, de Melo AC, Shparyk Y, Rakhmatullina I, Bondarenko I, Colombo N, Svintsitskiy V, Biela L, Nechaeva M, Lorusso D, Scambia G, Cibula D, Póka R, Oaknin A, Safra T, Mackowiak-Matejczyk B, Ma L, Thomas D, Lin KK, McLachlan K, Goble S, Kristeleit R. Rucaparib versus chemotherapy for treatment of relapsed ovarian cancer with deleterious BRCA1 or BRCA2 mutation (ARIEL4): final results of an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2025 Feb;26(2):249-264. doi: 10.1016/S1470-2045(24)00674-0.