Expert: Consider Dose Intensity With PARP Inhibitors for Ovarian Cancer

Researcher Bradley Monk, MD, spoke with Pharmacy Times about new data from the ATHENA-MONO trial presented at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting. The trial is investigating the use of rucaparib as maintenance treatment following response to front line chemotherapy in patients with ovarian cancer.

Bradley Monk, MD: Like all PARP inhibitors, the adverse reactions are sort of threefold: [gastrointestinal], fatigue, and bone marrow. And that was seen. Again, most were mitigated with supportive care, interruption, or dose reductions. Unique to rucaparib is a transient transaminitis that resolves without dose modification. There were no cases that met the definition of Hy’s law.

One of the other interesting things about ATHENA-MONO generally, but rucaparib specifically, is the dosing flexibility: 600 mg, 500 mg, 400 mg, 300 mg. And in fact, 80% of the patients—greater than 80% of the patients—could maintain the higher dose of 500 mg or 600 mg. And that was irrespective of age or weight, which is unique, I think, to this particular study. So, dose intensity probably matters in PARP maintenance treatment and flexibility for patient convenience and tolerability also matters, and that was shown here. There was no decrement in the patient experience. This was demonstrated by looking at the FACT-O, the functional assessment of cancer therapy, the ovarian sub score, and this was monitored carefully with high completion, high compliance rates with no decrement.

So, basically rucaparib first line maintenance treatment significantly improved [progression-free survival] irrespective of HRD status. Patients with measurable disease at baseline have further tumor reduction with rucaparib, the safety profile was consistent with prior studies, and the patient-reported outcomes are similar between rucaparib and placebo. At this time, overall survival is immature. At the data cutoff, 24.7% of the patients had a death event and we will continue to monitor this closely in an analytic fashion, as I described.

I'd like to thank ENGOT, the GOG, the sponsor, and most importantly, the patients and their families. But also, the broad collaboration and Rebecca Kristeleit at Guy’s and St. Thomas’ NH Foundation Trust in London, and Keiichi Fujiiwara, who is my Japanese co-PI. So, this presentation was published simultaneously online in the Journal of Clinical Oncology, I invite you to review that manuscript. Thank you for spending a few minutes with me today. And so long for now.