First-Line PARPi Maintenance in Advanced Ovarian Cancer - Episode 5

The Future of Care in Advanced Ovarian Cancer

December 17, 2019

Wendel Naumann, MD:I think the PARP [poly ADP ribose polymerase] inhibitors in general are probably a good treatment for all patients. We certainly think that these are as effective as chemotherapy, that we do have some response in patients with platinum resistance, particularly in combination. We now have data that suggest in patients who are platinum sensitive that PARP inhibition is probably as good as non-platinum-based chemotherapy. I think this opens the opportunity for patients to have non-chemotherapy-based treatment. I don’t know that we will ever get there in the primary setting, but certainly in the recurrent setting I think this is a realistic opportunity for patients to avoid the adverse effects of cytotoxic chemotherapy.

If patients progress on niraparib while they’re on maintenance, it depends a little bit on when they progress. Generally, if patients progress quickly, we go to single-agent chemotherapy. If patients progress more than 6 and perhaps 12 months out, we would go to platinum combination chemotherapy. Now in the PRIMA trial, the dosing was for 3 years. So I think the unknown question is, if somebody is more than 3 years out, has come off their PARP inhibitor, what do we do when they recur? Do we re-treat them with chemotherapy and then follow them with the maintenance PARP, like the NOVA trial or the ARIEL trial? We don’t know the answer to that. There are certainly ongoing trials that are trying to address this, but I think the problem is now we have had a fundamental shift in our primary therapy and it’s very difficult to predict what we’re going to do now in the recurrent setting.

Obviously, the highest unmet need in ovarian cancer is in the platinum-resistant space. Every patient who has a recurrent ovarian cancer is going to eventually become platinum resistant. We have very few effective treatments…. Response rates to therapy in the platinum-resistant setting are generally less than 20%. So as patients progress, they become more resistant to chemotherapy, cytotoxic chemotherapy, PARP inhibition, VEGF inhibition, anything that we can throw at the tumor. So, we really need better ways to attack the cancer. I think that there is some hope that we will be able to reverse some of the platinum resistance in the future with things like Wee1 inhibitors or perhaps combination PARP inhibition and immunotherapy or PARP inhibition and VEGF inhibition. But I don’t think we have any good answers, and that’s certainly a high unmet need.

In terms of PARP inhibition, I think that the big hurdle is just getting experience with this. Once people get on these medicines and you see how well these patients do, it’s very hard not to recommend these as treatment options, particularly in the HRD [homologous recombination deficient] patient population. I think it’s critical in theBRCApatient population that we follow chemotherapy with PARP inhibition because I really do think there’s going to be a significant survival advantage in that patient population and maybe even a higher cure rate.

Are we going to cure more patients with HRD? We probably are. It’s going to be difficult and we won’t know that for some period. I think for the HR-proficient patients, that’s going to be a high unmet need if you look at the PRIMA trial. And again, these patients were high risk to begin with. They had residual disease after surgery. These patients are HR-proficient, which means that they often don’t respond well to chemotherapy, and their median PFS [progression-free survival] was under 6 months. So the average patient who is HR-proficient is going to be platinum resistant, and that’s a tough patient population, particularly if patients are young.

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