Future Directions in High-Risk Ovarian Cancer

Ramez N. Eskander, MD: This is an incredibly exciting time for us in the ovarian cancer space. Just in a 2-month span, we’ve had 2 frontline drug approvals. The PRIMA results resulted in the approval of maintenance niraparib for an all-comer population in the frontline setting for patients with advanced stage III or IV high-grade ovarian carcinoma. The PAOLA-1 trial resulted in the approval of the combination of bevacizumab and olaparib in the homologous recombination deficient population inclusive of patients with BRCA mutations, again in stage III or IV disease. We also have several PARP approvals in the platinum-sensitive recurrent environment. So we have several options that we didn’t have just a short while ago.

We do still have some important questions to answer. We know that immunotherapy as a single agent when combined with chemotherapy has been disappointing in patients with advanced-stage ovarian cancer. Our hope is to design combination approaches that may augment response. There are several frontline studies looking at combinations of PARP inhibitors plus immunotherapy or immunotherapy plus antiangiogenic therapy, and some triplet studies are looking at antiangiogenic therapy, PARP inhibition, and immunotherapy to try to see whether we can expand the efficacy of these agents. Again, the goal is to get a meaningful response and provide opportunity for as many of our patients who are diagnosed in the front line as possible.

If we look at just homologous recombination deficiency and BRCA mutation, we capture about half of those patients who have high-grade advanced-stage disease. Well, we want to try to benefit the remaining 50%, and that may lie in these combination approaches that are actively being studied in frontline clinical trials. We’re awaiting the results of these studies. Hopefully they will inform future treatment opportunities for a patient population that continues to have a significant unmet need.

Transcript edited for clarity.

Case: A 71-Year Old Woman With High-Risk Ovarian Cancer

Initial presentation

• A 71-year old woman presented to her PCP for a routine annual checkup, she complains of increasing fatigue
• PMH:
  • Hypertension, controlled on a thiazide
  • 2017 diagnosed with stage IV ovarian cancer; BRCAwt; underwent TAH/BSO, lymph node dissection, with suboptimal debulking; treated with paclitaxel/carboplatin/bevacizumab followed by maintenance bevacizumab; achieved CR

Currently

• CA-125, 456 U/mL
• Chest/abdomen/pelvis CT with contrast shows a suspicious lung lesion
  • Lung biopsy confirmed recurrent epithelial ovarian cancer
• Molecular testing showed HRD+, LOH high
• ECOG: 0

Treatment and Follow-Up

• She was started referred to an oncologist and started on carboplatin/doxorubicin, treatment was well tolerated for 4 cycles; CA-125 35 U/mL;
  • Rucaparib 300 mg BID maintenance was initiated
• At 2 months follow-up
  • CA-125 was undetectable
  • Chest/abdomen/pelvis CT showed no gross masses or nodes
  • Pelvic exam was unremarkable