Dr Kristeleit on the ATHENA-MONO Trial in Ovarian Cancer

Rebecca Kristeleit, BSc, MBChB, MRCP, PhD, consultant medical oncologist, clinical senior lecturer, Department of Oncology, University College-London Cancer Institute, discusses the rationale for conducting the phase 3 ATHENA-MONO trial (NCT03522246) in newly diagnosed patients with advanced ovarian cancer, highlighting the implications of the 3-year follow-up data derived from the study.

Previous observations and hypotheses have indicated that maintenance therapy may confer survival benefits to women with advanced ovarian cancer who achieve a complete or partial response following first-line treatment comprising surgery and chemotherapy, Kristeleit begins. Notably, data from various studies have indicated that these survival outcomes can vary based on molecular status, as demonstrated with other PARP inhibitors, including rucaparib (Rubraca), in both the first-line and recurrent settings, she states. The ATHENA-MONO study evaluated whether women with advanced ovarian cancer would derive benefit from receiving rucaparib maintenance therapy for up to 2 years, Kristeleit adds. The study investigated this potential benefit with rucaparib maintenance therapy irrespective of homologous recombination deficiency or BRCA mutation status to reveal the treatment’s efficacy in a broad patient population, according to Kristeleit.

At the 2024 SGO Annual Meeting, investigators presented the results of a long-term follow-up analysis of ATHENA-MONO focusing on time to first subsequent therapy, second progression-free survival, and overall survival outcomes, Kristeleit reports. This ad-hoc analysis primarily supported an application to the European Medicines Agency seeking approval for the first-line use of rucaparib in patients with advanced ovarian cancer.

Questions have arisen regarding the toxicities associated with frontline rucaparib in this trial, she continues. Notably, rucaparib has undergone extensive investigation as a maintenance therapy in the recurrent setting, Kristeleit notes. Comparatively, the safety findings observed in the first-line setting revealed no new safety signals, Kristeleit elucidates. Although the incidence of myelodysplastic syndrome and acute myeloid leukemia with rucaparib were consistent with the class effect of PARP inhibitors, there was no significant difference in the incidence of these secondary hematologic malignancies in the rucaparib arm compared with the placebo group, Kristeleit says. Overall, the toxicity profile of rucaparib was deemed manageable, offering reassurance regarding its safety as a first-line treatment for patients with advanced ovarian cancer, she concludes.