Maintenance and Recurrent Treatment Options for Ovarian Cancer

Benedict Benigno, MD:Maintenance therapy is something I have waited for my entire career. Many years ago, many of us gave monthly doxorubicin or monthly paclitaxel for a year as maintenance therapy until we learned that it really did not affect progression-free or overall survival, so we stopped that. Bevacizumab came along. I personally do not use it as maintenance therapy in first-line approaches. However, olaparib has recently been approved as maintenance in the first-line setting. Unfortunately, the patient must have a mutation on theBRCAgene, either germline or somatic, in order to be eligible for first-line maintenance.

Twenty-five percent of patients with ovarian cancer will have a mutation on theBRCAgene, 18% germline, which means that it is present in every cell on the body and is inherited. And in 7%, the mutation is somatic, which means it’s present only in the cancer cell and is not inherited.

There are many trials going on. I am particularly interested in maintenance therapy, combining a PARP inhibitor with an immunotherapy drug. We have trials in progress at this time, but there is nothing out there right now that I can use in the first-line setting that would include an immunotherapy drug.

It’s been the most exciting data that I have encountered since the advent of platinum in the 1970s. And now I’m showing you my age. I was not only alive in the 1970s but actually working in the 1970s. And when I started doing this work, we would operate on the patient, and all we had was Alkeran [melphalan], an alkylating agent by mouth, and invariably it would fail. And then platinum came along and all of a sudden we were getting these extraordinary progression-free intervals.

What I would do in the first-recurrence setting is I would do something different from what was done for this patient. My regimen of choice in the first-recurrence setting is monthly doxorubicin and carboplatin, and it is an excellent regimen. It is very well tolerated. It has excellent results. They do not lose their hair. They have very little peripheral neuropathy. The only thing different is you have to be careful of what’s known as palmar-plantar erythema: a redness, and sometimes excoriations, of the palms and the soles.

And I frequently add Avastin [bevacizumab] to that regimen. After 6 cycles, it’s time to stop the doxorubicin and carboplatin. At that time, I love to give a PARP inhibitor as maintenance therapy. I don’t know if I should say this or not, but the insurance company forgets that it has approved Avastin. And I get a PARP approved as maintenance therapy, and I sometimes give the PARP inhibitor with the bevacizumab, a great deal of success with that. And the adverse effects do not cross over. The combination is very well tolerated. I sometimes have to stop 1 of the drugs, but it’s for reasons that I would have to stop the drug anyway and not because of the comingling of the 2 drugs.

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