Choices for Second-Line Maintenance Therapy

Benedict Benigno, MD:If a patient has a mutation on theBRCAgene, either germline or somatic, she will have a much greater chance of responding to not only a PARP inhibitor but also a platinum-based regimen. When PARP inhibitors first became available, I could use them only in theBRCA-mutated setting. What I would do if they wereBRCA-negative, is I would send the tissue to Myriad Genetics, Inc, and they would do the HRD [homologous recombination deficiency] testing. If a patient isBRCA-negative but HRD-positive, in my opinion she has about as much of a chance of responding to a PARP inhibitor as though she had a mutation on theBRCAgene.

It absolutely would be my choice in the second-line setting, which is the first recurrence. I said I would give doxorubicin and carboplatin, and at that time I would give a PARP inhibitor as maintenance. Now the NOVA trial is very, very interesting, and my practice accessed the largest number of patients, accessed to the NOVA trial. And I was 1 of the authors in theNew England Journal of Medicinepaper. Briefly, all the patients were adults. They had epithelial cancers of the ovary, fallopian tube, or peritoneum, all the same process. They were in partial or complete remission to a platinum-based regimen, and they were randomized 2:1 to receive either niraparib or a placebo.

And there were 553 patients in this trial; 203 had a mutation on theBRCAgene, and 350 wereBRCAwild type, which means they did not have a mutation on theBRCAgene. It was a very excellent trial, and those patients who wereBRCAwild type were broken down into whether they were HRD-positive, homologous recombination deficient positive, or also whether they were somatic. If they wereBRCAwild type, were they positive? Did they have aBRCAmutation in the cancer cell itself that would make them somaticBRCA-mutated?

Basically, with the TWiST analysis that had to do with the quality of life, and it had to do with the time of the adverse events, subtracted from the progression-free interval. When you were given the niraparib, they had a much longer time without symptoms or toxicity. TWiST means time without symptoms or toxicity. If you’re going to deal with these patients and take care of them properly, you’d like to be able to choose the best treatment for them but also try to mollify, somewhat, the adverse effects if that is possible.

Well, the endpoint, they were treated until toxicity or until recurrence, unacceptable toxicity or recurrence.

Transcript edited for clarity.

Case: A 58-Year-Old Female With Progressive Ovarian Cancer

H & P

• A 58-year-old female presents to the clinic for bloating, pelvic pain, early satiety, and urinary urgency. She reports intolerance to strenuous activity at the gym for the past four months but is still able to carry out daily activities such as work, and house chores.
• PE: controlled HTN, abdominal distension;
  • BP: 130/70 mmHg
  • ECOG: 1

Imaging

• CT with contrast of the pelvis, abdomen, and chest reveals bilateral serous cystadenocarcinomas

Biopsy and Labs

• Pathology: high-grade serous carcinoma, epithelial ovarian cancer
• BRCA1-/2wt
• HRD/+
• CA-125: 280 U/mL

Treatment

• Diagnosis: stage IV ovarian cancer
• Patient underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and tumor debulking
• Received IV paclitaxel and carboplatin and bevacizumab, 6 cycles

Follow-up

• CA-125, 43 U/mL upon completion of 6 cycles chemotherapy
• Ten months later at routine follow up, patient presented with recurring symptoms; CA-125, 565 U/mL
• Started on carboplatin/paclitaxel for 6 cycles plus bevacizumab
• Patient achieved a partial response, started on niraparib maintenance therapy
• Four months later:
  • CBC: WNL, SCr: 0.8, AST: 10 u/L, ALT: 7 u/L, and ANC: 1.7 x 10⁹/L
  • BP, WNL
  • ECOG 1