Approaching Treatment of Newly Diagnosed or Recurrent Ovarian Cancer With PARP Inhibitors

Although the era of personalized medicine has arrived, there remains much to be discussed regarding platinum sensitive disease among patients with newly diagnosed or recurrent ovarian cancer, explained David O’Malley, MD, during a presentation at the Society of Gynecologic Oncology annual meeting. When looking at some of the market data, only approximately 40% of patients with platinum sensitive disease are receiving a poly (ADP-ribose) polymerase (PARP) inhibitor in the first-line setting.

When conducting an exploratory analysis of data from the ARIEL3 trial, O’Malley noted it was important to assess the clinical biomarker of platinum response. O’Malley additionally explained that the assessment of platinum response may be more important than the assessment of platinum sensitive disease or even homologous recombination deficiency (HRD).

“These patients come in with measurable disease often. So, we wanted to see the clinical biomarker for how that worked,” O’Malley said. “In BRCA, [complete response (CR)] data showed a hazard ratio [(HR)] of 0.3, HRD had a HR of 0.37, and the intent-to-treat population had an HR of 0.33. If you have a complete response, I don’t care if you’re [homologous recombination proficient (HRP)] in the platinum sensitive, I’m going to give that patient PARP maintenance.”

O’Malley noted that in treatment of patients with a BRCA mutation, to not offer a patient who has received treatment in the first line with a PARP inhibitor in the second line is problematic.

“It could be considered malpractice, and I don’t say that lightly,” O’Malley said. “Now, if we look at the HRD population, once again, with a [partial response (PR)] at a HR of 0.29. Again, look at the intent-to-treat population [with a HR] at 0.36. If you have the clinical biomarker of response to platinum doublet and they haven’t had a PARP inhibitor, to me that’s a really important consideration.”

In patients who progress while on their platinum therapy in the platinum sensitive setting, O’Malley noted that may be a strong indication that the patient may not be a good candidate for a PARP inhibitor.

O’Malley also noted that he has heard colleagues express hesitation to pursue treating patients with PARP inhibitors due to the high rates of adverse effects (AEs). However, O’Malley noted that the AEs of disease recurrence are far more severe, shining a light on the necessity to pursue treatment with the most effective drug available.

“If you keep the disease away, you do better from a [patient reported outcomes (PRO)] standpoint,” O’Malley said.

Furthermore, if you have a patient with BRCA mutation in the platinum sensitive setting, O’Malley noted that you have to offer them a PARP inhibitor.

“The clinical biomarker of the platinum response, CR—I would argue—behaves similarly to our BRCA patients with a HR of 0.3,” O’Malley said. “We’ll see HRP data in the future, but remembering those HRD patients, if you’re not going to pay attention to the clinical biomarker, clearly you need to talk to them about a PARP [inhibitor].”

In platinum sensitive and resistant disease, O’Malley explained that the ARIEL4 trial also demonstrated that treatment with a PARP inhibitor provided stronger outcomes than treatment with chemotherapy.

“But we also need to get smarter at predicting those who are not going to respond. I talked about the clinical biomarker of platinum sensitivity, but hopefully in time with circulating DNA, we’re going to be able to identify these converging mutations, even in BRCA patients and those we should not utilize PARP therapy for,” O’Malley said. “Also, just as a reminder, we talk so much about first line therapy, yet more than half of our patients will not have been exposed to a PARP [inhibitor] in the first line, so we need to think about it in the platinum sensitive setting.”

REFERENCE

O’Malley D. Treatment of Recurrent OC; Ongoing Research Efforts with PARP Inhibitors for Newly Diagnosed Disease. Society of Gynecologic Oncology 2022; March 19, 2022; Phoenix, AZ.