Front-Line Treatment Options for Ovarian Cancer

At the Great Debates & Updates in Women’s Oncology meeting, Bradley Monk, MD, discussed molecular testing and advancements in front-line treatment for patients with advanced epithelial ovarian cancer.

Transcript:  

Greetings and welcome my name is Brad Monk, I'm a gynecologic oncologist here in Phoenix, Arizona, Professor at both medical schools here— University of Arizona, Phoenix, and Creighton University, Phoenix.

I think all of us know that in treating ovarian cancer that the best option for patients is in the front-line, in fact we've learned that we can cure some patients with widely metastatic cancer. The first discovery of course, was the addition of bevacizumab to the standard chemotherapy backbone which was carboplatin and paclitaxel, published in the New England Journal of Medicine in 2011, FDA approved in 2018, and that was really exciting— but it was not enough, and there was no biomarker.

Now we have poly ADP ribose polymerase inhibitors (PARP inhibitors), and these are medications that create single-stranded DNA breaks that ultimately lead to double-stranded breaks and if the cell cannot repair a PARP–inhibitor-induced double-stranded break, then the cell dies. Those patients have homologous recombination repair deficiency (HRD) or a BRCA mutation because the BRCA genes are pivotal in that process. This journey started with the publication of SOLO1/GOG3004 but it was in BRCA-only patients, both somatic and germline.

That study has matured, is globally approved, and now there is a survival advantage — but we needed to do better. We needed to allow all patients regardless of molecular signature and BRCA status to have access.

We did that with another GOG study called PRIMA/ENGOT-OV26/GOG-3012, also published in the New England Journal of Medicine and that was an all-comer indication. We don't have overall survival data yet for PRIMA, but we have expanded it even further by combining PARP inhibitors and bevacizumab together but only in the homologous recombination repair deficient subset. That study is called PAOLA-1, also published in the New England Journal of Medicine, and that also has a survival advantage. Finally, a confirmatory trial called ATHENA (GOG-3020/ENGOT-ov45) for rucaparib.

We have 3 PARP inhibitors: olaparib, niraparib, and rucaparib alone or in combination with bevacizumab in the front-line treatment of ovarian cancer. How do you sort that out? Well, the first answer is yes, every patient unless there's a contraindication, should get front-line maintenance. If they have a BRACA mutation they can get all 3 PARP inhibitors, if they have a HRD they can get all 3 PARP inhibitors, but olaparib requires bevacizumab. Even if they don't have HRD they can still get niraparib according to PRIMA or rucaparip according to ATHENA and this is NCCN recommended and according to the ASCO guidelines.

Let's not leave anyone behind, let’s make sure that we allow as many patients as possible the benefit when they are diagnosed with advanced epithelial ovarian cancer so that they can live better and additionally live longer.

Source:

Monk, BJ. Updates in molecular testing and front-line treatment in ovarian cancer. Presented at Great Debates & Updates in Women’s Oncology; November 1-3, 2023. Virtual