First-Line PARPi Maintenance in Advanced Ovarian Cancer - Episode 3

Initial and Maintenance Treatments for Ovarian Cancer

December 17, 2019

Wendel Naumann, MD:HR [homologous recombination]-proficient versus HR-deficient is a marker for biologic aggressiveness of the tumor and response to chemotherapy.

We know that HR-proficient tumors relate to poor prognosis with ovarian cancer. These patients don’t respond to chemotherapy as well. And while they got a benefit for maintenance PARP [poly ADP ribose polymerase] inhibition, that benefit was somewhat limited. We had an improvement in progression-free survival of only about 2 to 3 months. Now having said that, there is a group of those patients who get a significant benefit for a long period. And I think we don’t do a good job of separating those patients out.

For patients who are HR-deficient, I think that the PARP inhibitors are an excellent choice for maintenance therapy. We know patients are going to get a very good benefit, very similar to the patients with theBRCAmutations.

Niraparib has been shown in the PRIMA trial to benefit all patients after chemotherapy and surgery. The amount of benefit is based on the mutation or the HR deficiency. The more HR-deficient these patients are, the better the benefit that they get from the maintenance niraparib.

Niraparib basically prevents DNA repair. Cells that are HR-deficient have a hard time repairing the DNA damage because the homologous repair mechanism is broken. And if we can inhibit PARP, that prevents these cells from repairing the DNA damage. And therefore there is a selective benefit to this that is directed toward the cancer cells and not toward the normal cells since the normal cells retain some of their homologous repair mechanism.

Transcript edited for clarity.


Case: A 54-Year-Old Female With Ovarian Cancer

H & P

  • 54-year-old female presents with abdominal pain and bloating
    • Pathology: High-grade, stage III, epithelial ovarian cancer of the right ovary, and positive for numerous small (<0.7cm) pelvic and para-aortic lymph nodes disease
    • CA-125, 305 U/mL
  • Imaging
    • CT with contrast of the pelvis, abdomen, and chest revealed a right adnexal 2.9-cm mass, no ascites or pleural effusion noted
  • Treatment
    • Patient underwent exploratory laparotomy with unilateral salpingo-oophorectomy, pelvic and para-aortic lymph node dissection
      • Status post-surgery: macroscopic residual disease (R2), 1.2cm lesion
      • Received second cytoreduction surgery
    • Germline molecular testing showed HRD +,BRAC1alteration
    • Initiated IV/IP paclitaxel/cisplatin
    • Initial post treatment CA 125, 48 U/mL
    • Started on niraparib maintenance therapy
  • Follow-up:
    • CA 125, 25 U/mL upon completion of chemotherapy (6 cycles)
    • CT at 2.5 months post-surgery, no gross pelvic masses; chest CT unremarkable
    • Unremarkable pelvic exam
    • ECOG: 0