Robert Coleman, MD, Texas Oncology, The US Oncology Network, Woodlands, TX, discusses findings from the phase 3 ATHENA-MONO trial which compared rucaparib vs placebo for maintenance therapy in patients with ovarian cancer. The study reported rucaparib monotherapy is an effective first-line maintenance therapy for these patients.

These findings were presented at the 2022 ASCO Annual Meeting.

Transcript:

I'm Rob Coleman, I'm a gynecologist oncologist in Houston, Texas, and I serve as the chief scientific officer for US Oncology Research, as well as a gynecologist oncologist with Texas Oncology.

We're really pleased to be able to present the late breaking abstract ATHENA-MONO, which was evaluating the efficacy of rucaparib as a maintenance therapy in patients with advanced stage ovarian cancer who had responded to a platinum-based therapy. This trial was a long time coming, and we were very excited to be able to present the results, but the motivation for doing this trial actually capitalized on some experience that we had in the recurrent setting in a similarly constructed trial for patients with platinum sensitive recurrent over in cancer in that trial called ARIEL3.

And in that trial, we were able to demonstrate that there was efficacy in a biomarker annotated population that was first constructed in patients whose tumors had a mutation in BRCA. Those that were BRCA wild type, but had homologous recombination deficiency signature by an FDA-approved test, in this case, by loss heterozygosity in the Foundation Medicine assay, and then ultimately, in the intent to treat population. Capitalizing on that data, we felt it was probably very relevant to study this in the frontline setting. And that's what the point of this particular trial was.

We wrote a trial that would take patients with newly diagnosed ovarian cancer, who had responded to their frontline therapy if they had measurable disease and what we did is we randomized those patients. The trial itself has actually 4 arms because we will be also evaluating the combination of rucaparib and nivolumab. It was randomized against 2 single agent arms and placebo. This particular trial, ATHENA-MONO, was looking at rucaparib versus placebo.

Now, the trial, with respect to the biomarker subgroup, we constructed it just slightly differently. We collapsed the patients whose tumors were had a BRCA mutation and the patients whose tumors had ophthalmologist for combination deficiency signature, regardless of their BRCA status, and called that HRD test positive. And then, if that analysis was positive, then we passed all of the alpha for the analytics into the intent to treat population. So not surprisingly, the trial was very positive. We showed a reduction in the hazard for progression or death by over 50%, the hazard ratio 0.47 in that HRD test positive cohort of patients. And in the ITT population, just slightly less positive with the hazard ratio, just above 0.5.

We felt that, given this population of patients, which represent what we feel is a very realistic real-world population. It was inclusive of a lot of subgroups that we would see in the day-to-day, as opposed to the data that was available ongoing right now, which was the SOLO-1 trial, which was exclusively done in patients with BRCA-positive tumors, or the PRIMA trial, which was done in patients who had higher risk, prognostic risk patients, and the POLO-1 trial, which was done in combination with bevacizumab. This, we felt, was a more realistic, straightforward, analytical population of patients with advanced-stage ovarian cancer, who were good candidates for a maintenance strategy.

Importantly, we also found no new safety signals. We've had a lot of experience with this drug in the recurrent setting, both as a treatment and as a maintenance strategy. We didn't see anything new. And we are, obviously, very excited with the robust results seen in this study. And we hope, as this goes forward, that this will represent a new option for our patients. And so more to see on how that comes.

Of course, we're also very interested in seeing what happens with ATHENA-COMBO trial, which will be looking at that hypothesis as to whether or not the addition of an immune checkpoint inhibitor could actually augment the effect even more.

With respect to the trial population, we're very excited that we feel like this represents our real-world population. We're very confident in the results as they would apply, let's say, outside of the clinical trial setting, but I don't want to under stress the need for clinical trials. In this frontline setting, where we have the highest proportion of curable patients, it is so important that we continue to push the needle on coming up with the most effective therapies, and hopefully, to identify those biomarkers that identify the patients that are most likely to benefit from these studies. We need to obviously balance these strategies against all the toxicities, including financial toxicity.

I'm proud that we are part of the narrative that's driving those studies and answering those questions. And so, if anything, this should give us even more robust momentum to continue that research narrative.

Source:

Monk BJ, Parkinson C, Lim MC, et al. ATHENA–MONO (GOG-3020/ENGOT-ov45): A randomized, double-blind, phase 3 trial evaluating rucaparib monotherapy versus placebo as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer. Presented at: ASCO Annual Meeting; June 3-7, 2022. Chicago, IL, and virtual. Abstract LBA5500.