Niraparib Monotherapy in Late-Line Ovarian Cancer

Amina Ahmed, MD:The QUADRA trial was a trial that looked at women who had recurrent ovarian cancer who were heavily pretreated, 3 to 4 lines of treatment prior, who were HRD [homologous recombination deficiency] positive specifically, irrespective of their genomicBRCAstatus. And the majority of patients in this study, over 70%, were either platinum refractory or platinum resistant, and their response rate to single-agent niraparib was 28%. That’s a significant response rate in that heavily pretreated population.

Prior to QUADRA, patients who wereBRCApositive could be treated with PARP inhibitors, specifically olaparib or rucaparib—rucaparib as a third-line agent, and olaparib as a fourth-line agent. But these patients had to beBRCApositive. QUADRA is practice changing. These are patients who are platinum refractory who are notBRCApositive who had a significant response rate, even though the majority of patients are platinum resistant and heavily pretreated.

Currently, in my clinical practice, I now can offer patients who areBRCAnegative PARP inhibitor treatment. Prior to QUADRA, patients who wereBRCApositive could receive PARP inhibitor treatment, specifically third and fourth line and specifically rucaparib or olaparib. Patients who wereBRCAnegative really, primarily saw PARP inhibitor treatment in a recurrent setting after platinum treatment. Now, though, they can see PARP inhibitor treatment as treatment, and even if they’re heavily pretreated third or fourth line, it doesn’t actually matter.

The FDA currently has approved niraparib monotherapy in patients who have recurrent ovarian cancer, platinum sensitive or platinum resistant,BRCAnegative but HRD positive. And that was the primary objective of QUADRA. The inclusion was HRD-positive patients specifically. The response rates were in patients who were HRD positive or HRD negative, but currently the FDA has approved patients who are HRD positive.

Patients who are selected for niraparib monotherapy would be patients who areBRCAnegative, and I know their HRD status and particularly if they’re HRD positive who are either platinum resistant or platinum sensitive in a recurrent setting.

Patients who are heavily pretreated obviously eventually become platinum resistant, and response rates to all the treatments are much lower and sometimes less than 15%. So the response rates are quite low. In QUADRA, the response rate was 28%, and these are in patients who are heavily pretreated, the majority platinum resistant, platinum refractory. And so that’s really a huge win for patients with ovarian cancer.

Transcript edited for clarity.

Case: A 56-Year-Old Female With Recurrent Ovarian Cancer

• 56-year-old female diagnosed with stage IV ovarian cancer (2016)
  • Weight: 105-lb, height: 5’6”, BMI of 16.9
  • Pathology: high-grade serous carcinoma, epithelial ovarian cancer
  • CA-125: 475 U/mL
  • CT with contrast of the pelvis, abdomen, and chest revealed a 3.5-cm mass in the right ovary and peritoneal carcinomatosis
  • Patient underwent suboptimal debulking surgery; residual disease 1.5 cm
  • Received IV/IP carboplatin/paclitaxel (6 cycles); achieved complete response
• 1 year later (2017) symptoms returned; CA-125, 265 U/mL; ECOG: 1
  • Received carboplatin/paclitaxel (6 cycles) and bevacizumab; achieved good partial response; CA-125, 45 U/mL; continued on bevacizumab maintenance
• 8 months following second-line therapy (2018), again presented with symptoms; CA-125, 550 U/mL; ECOG: 0
  • Received carboplatin/gemcitabine (6 cycles); CA-125, 54 U/mL; achieved complete response
• Currently:
  • CA-125, 585 U/mL
  • CT shows 2.7 cm right lower lobe lung mass
  • ECOG: 0