Study Explores New Treatment With PARP Inhibitors in Recurrent Ovarian Cancer

Kathleen G. Essel, MD

The benefits of PARP inhibitors are well established for patients with ovarian cancer and researchers are looking for ways to expand the role of PARP inhibitors in new patient populations. Ovarian cancer patients likely to benefit from these treatments.

A group of researchers is investigating the possibility of challenging patients with ovarian cancer with PARP inhibitors later during treatment, when their disease has become recurrent. As the first to examine patients with new challenges with PARP inhibitors, the researchers found that patients previously exposed to PARP inhibitors did not develop resistance and could therefore receive repeated treatment with inhibitors of PARP. PARP.

The small retrospective study focused on 22 patients with epithelial ovarian cancer who had received at least two lines of prior therapy containing a PARP inhibitor. These patients were treated again with one of 3 FDA-approved PARP inhibitors: olaparib (Lynparza; n = 6), niraparib (Zejula; n = 10) and rucaparib (Rubraca). n = 6); 3 patients received a new treatment in maintenance treatment. After reprocessing, patients had the best responses of 3 partial responses (13.6%) and stable disease in 13 patients (59.1%). Three patients (13.6%) had progressive disease. It should be noted that all the patients who obtained a partial response had a BRCA mutation.

Kathleen G. Essel, MD, Stephenson Cancer Center of the University of Oklahoma, a researcher in gynecologic oncology, is involved in ongoing research on the role of treating cancer patients with cancer. Ovarian with PARP inhibitors. In an interview with Targeted oncologyShe explained the existing and developing information that supports the use of PARP inhibitor reprocessing in ovarian cancer and the information that remains to be known about the subject.

TARGETED ONCOLOGY: What kind of data do we have to challenge patients with PARP inhibitors?

Essel: At present, information about patients with new challenges with PARP inhibitors is very limited. In fact, we have no data. Our study was the first to address the problem of patients with a new PARP inhibitor. This is an area of ​​active research right now as we now have indications for PARP inhibitors in the first line and for BRCA mutation carriers. And we are currently looking for a prospective, randomized clinical trial to see whether challenging patients with PARP inhibitors is beneficial or not. But at this point, there is no data published on this subject.

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

Essel: We currently have a prospective randomized clinical trial, OReO, that is underway [in Europe] We look forward to seeing the results of this study. We look forward to patients with olaparib, a PARP inhibitor, and recurrent recurrent ovarian cancer sensitive to platinum. [This] was a retrospective study of 4 different institutions, covering all patients who had been treated again with PARP inhibitors.

TARGETED ONCOLOGY: Do you think it's best to treat patients with a PARP inhibitor after another or to add another form of treatment between the two?

Essel: The data we have [around this] is very limited. I think it would be better to leave a gap between the two. But all this is anecdotal and does not rely on any data.

TARGETED ONCOLOGY: Are there some patients who would not respond to a new treatment with a PARP inhibitor?

Essel: We do not know the answer to this question. In our retrospective study, we examined a variety of patients. Patients who responded best to subsequent treatment with a PARP inhibitor were patients BRCA mutation and had been exposed to a PARP inhibitor with their first-line treatment. However, we examined the group of patients who received a progressive PARP inhibitor and really thought that this group of patients would not do well with a new treatment with the PARP inhibitor. But [those] the patients actually [did] well. The disease was stable in five out of eight patients, some of whom were durable. Three of these patients remained on PARP inhibitors for more than a year before progressing, which was quite remarkable.

So we need to find some sort of marker, whether it's a blood test or a clinical marker, to tell us which patients will benefit the most from PARP inhibitor treatment just to limit the exposure to these drugs in patients would not necessarily benefit. But, from the small retrospective study we did, we found nothing to suggest that patients do not respond to the new treatment.

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

Essel: Inhibitors of PARP change the face of ovarian cancer and change the landscape. Last year, we had the results of SOLO-1, which gave us our first indication of PARP inhibitors on the front line. Over the next year, we expect to have three clinical trials that will explore the role of PARP inhibitors in the first-line treatment of ovarian cancer, regardless of BRCA status. So it's very exciting and I think it will completely change our approach to ovarian cancer and, hopefully, actually extend our progression-free survival and overall survival.

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