Subgroup Analysis in ATHENA-MONO Trial Shows Encouraging Results for Rucaparib in Ovarian Cancer

Blinded independent central review analysis also adds confidence to the findings.

Newly released results from the ATHENA-MONO trial investigating the use of rucaparib as maintenance treatment following response to front line chemotherapy in patients with ovarian cancer have shown promise, according to Bradley Monk, MD. Monk presented the data at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting.

Bradley Monk, MD: In the abstract, or in the presentation, I thought it was important to mention the [blinded independent central review; BICR]. The BICR is obviously blinded and adds confidence to what the investigator was seeing, even though the investigator was blinded by the placebo. And you can see that these secondary BICR endpoints were highly statistically significant, clinically relevant, and consistent with the investigator observations.

In the subgroup analysis, I want to highlight the HRD test negative [group]. Again, the diagnostic was the foundation [loss of heterozygosity, LOH] score greater than 16. You can see that the hazard ratio in the investigator was 0.65, it increased to 0.60 in the BICR analysis. In the bigger analysis, it was a 5.6-month improvement in progression-free survival from 6.4 to 12 months. This was perhaps the most exciting part of this study, adding confidence that in the HRD test negative subset that adding PARP inhibitors, specifically rucaparib, shows a clinical benefit. The benefit was consistent across all pre-specified subgroups, again, adding confidence. And I note that those patients who had residual disease or high-risk disease—meaning those that had neoadjuvant or stage 4 or PR or an elevated CA 125—continued to do well and even had a better hazard ratio and also had documented responders. The response rate in the HRD population to rucaparib was 58.8% and 48.8% in the intent-to-treat analysis. And these responders—again, almost all of them partial—were durable, with a median duration of response between 16 and 22 months. So, highly important that patients who finish 6 cycles of chemotherapy but still respond can have further clinical benefit if they are pivoted to a rucaparib opportunity.

Adverse reactions were common. Most were low grade. I already mentioned the discontinuation rate. There were 2 deaths due to a treatment-emergent adverse reaction in the rucaparib group—that's 0.5%—and none in the placebo group.