Novel Combination Strategies in Recurrent Ovarian Cancer

Bradley J. Monk, MD: Tom Herzog, in front line we did PRIMA (NCT02655016) and PAOLA (NCT02477644), which went beyond BRCA and it was great. Now we’re also looking in patients beyond BRCA in recurrent disease. We have the treatment indications: for rucaparib, it’s germline and somatic; for olaparib, two priors; three priors germline; and then there’s HRD, three priors for niraparib. There are opportunities for combinations in nonmolecularly signature groups. Tell us about those novel combinations, such as the combination of dostarlimab and PI3K [phosphoinositide 3-kinase], as well.

Thomas J. Herzog, MD:Niraparib plus dostarlimab, TSR-042 as I used to know it, is called MOONSTONE (NCT03955471), a phase 2 study. Drug combinations is really where we’re going, and you see that in front line, too. The idea of a checkpoint inhibitor with a PARP is that the PARP may increase tumor mutational burden and make a checkpoint inhibitor more effective, increasing tumor-infiltrating lymphocytes. You were talking about making a choice for platinum-sensitive disease, but maybe we don’t. If we look at AVANOVA (NCT02354131), which came out with niraparib plus bevacizumab, versus niraparib monotherapy, presented by Mansoor Raza Mirza, MD. The study showed the PFS [progression-free survival] was 11.9 versus 5.5 months, which is a significant improvement. There are a lot of things here in terms of combinations. Dr Konstantinopoulos presented, at ESMO [European Society for Medical Oncology] this year, olaparib plus alpelisib, which is a PI3 kinase AKT inhibitor, and it showed some really good data with relatively small numbers. We have combinations of VEGF with TKIs, so there are a number of studies going on.

In phase 1 and phase 2 of the TOPACIO (NCT02657889) trial, looking at niraparib plus pembrolizumab in platinum-resistant disease, the overall response of combined was 18%. These are platinum-resistant patients and the stable disease rate was very high at 33%.

I think there are a lot of combinations out there that are really appealing, and it points to the need to place these patients in clinical trials, because we have more combinations than we do patients. It’s really important that we put patients in clinical trials and figure out the very best combination for our patients.

Bradley J. Monk, MD: Thank you. We talked about the NCCN [National Comprehensive Cancer Network] Guidelines for front line, which preferred choice in recurrent disease is a clinical trial, to your point. Every time you enroll in a clinical trial, you are following the NCCN Guidelines at the highest level.

Transcript edited for clarity.