Study Explores Re-Treatment With PARP Inhibitors for Recurrent Ovarian Cancer

Kathleen G. Essel, MD

Kathleen G. Essel, MD

The benefit of PARP inhibitors has been well established for patients with ovarian cancer, and investigators are looking for ways to expand the role of PARP inhibitors to new populations of patients with ovarian cancer who may benefit from these therapies.

One set of researchers are exploring the possibility of re-challenging patients with ovarian cancer with PARP inhibitors later in the course of treatment when their disease became recurrent. As the first to examine re-challenging patients with PARP inhibitors, researchers found that patients who had prior exposure to PARP inhibitors did not develop resistance and could, therefore, receive repeat treatment with PARP inhibitors.

The small retrospective study looked at 22 patients with epithelial ovarian cancer who had received at least 2 lines of prior therapy containing a PARP inhibitor. These patients were re-treated with one of the 3 FDA-approved PARP inhibitors: olaparib (Lynparza; n = 6), niraparib (Zejula; n = 10) and rucaparib (Rubraca; n = 6); 3 patients received re-treatment as maintenance therapy. After retreatment, patients demonstrated best responses of 3 partial responses (13.6%) and stable disease in 13 patients (59.1%). Three patients (13.6%) had progressive disease. Of note, all patients who achieved a partial response had aBRCAmutation.

Kathleen G. Essel, MD, a gynecologic oncology fellow at the University of Oklahoma, Stephenson Cancer Center, is part of the ongoing research around the role of re-treating patients with ovarian cancer with PARP inhibitors. In an interview withTargeted Oncology, she explained the existing and developing information supporting the use of re-treatment with PARP inhibitors in ovarian cancer and the information that is yet to be known on the subject.

TARGETED ONCOLOGY:What kind of data do we have in re-challenging patients with PARP inhibitors?

Essel:Currently, information regarding re-challenging patients with PARP inhibitors is very limited. We actually don’t have any data. Our study was the first one to discuss re-challenging patients with PARP inhibitors. It's an area of active research right now since we now have indications for PARP inhibitors in the frontline and forBRCAmutation carriers. And we're actively looking right now with a prospective randomized clinical trial to see if re-challenging patients with PARP inhibitors is beneficial or not. But at this point, there is zero published data on this topic.

TARGETED ONCOLOGY:Are there trials currently ongoing that can help oncologists determine which patients to re-challenge with PARP inhibitors in the future?

Essel: Currently we do have a prospective randomized clinical trial, OReO, which is being conducted [in Europe] looking at re-challenging patients with the PARP inhibitor olaparib and platinum-sensitive recurrent ovarian cancer and we're all really excited to see the results of that. [This] was a retrospective study amongst 4 different institutions, looking at all patients who had been re-treated with PARP inhibitors.

TARGETED ONCOLOGY:Do you think it is best to treat patients with one PARP inhibitor after another or add another form of treatment in between?

Essel:The data that we have [around this] is very limited. I think that it would be better to have a gap in between. But that's all anecdotal and not based on any data.

TARGETED ONCOLOGY:Are there certain patients who would not respond to re-treatment with a PARP inhibitor?

Essel:We don’t know the answer to that. When we did our retrospective study, we had looked at a variety of patients. The patients who responded best with re-treatment with a PARP inhibitor were patients who had aBRCAmutation and had been exposed to a PARP inhibitor with their frontline therapy. However, we looked at the group of patients who received a PARP inhibitor to progression and really thought that this group of patients would not do well with re-treatment from the PARP inhibitor. But [those] patients actually [did] well. Five out of 8 patients ended up having stable disease, and some of those were durable. Three of those patients actually remained on the PARP inhibitor for over a year before progressing, which was quite remarkable.

So, we do need to find some sort of marker whether it's a blood test or a clinical marker to tell us which patients are more likely to benefit from re-treatment with PARP inhibitors just for the sake of limiting exposure to these medications in patients who wouldn't necessarily benefit. But, based off of the small retrospective study we did, we didn't find anything to suggest patients wouldn't respond to re-treatment.

TARGETED ONCOLOGY:What impact have PARP inhibitors had on ovarian cancer thus far?

Essel:PARP inhibitors are changing the face of ovarian cancer and changing the landscape. We, in the last year, had the results of SOLO-1 which gave us our first indication for PARP inhibitors in the frontline. In the next year we're expecting to have 3 clinical trials that will explore the role of PARP inhibitors in the frontline treatment of ovarian cancer regardless ofBRCAstatus. So, this is very exciting, and I think it's going to completely change the way that we approach ovarian cancer and hopefully really prolong both our progression-free and overall survival.

Reference:Essel KG, Behbakht K, Lai T, et al. PARPi after PARPi in epithelial ovarian cancer. Presented at: 2019 SGO Annual Meeting; March 16-19, 2019; Honolulu, HI. Abstract 7.