Frontline Therapy Options for Stage IV Ovarian Cancer

Ramez Eskander, MD: In patients who have advanced stage frontline ovarian cancer, the standard of care continues to be combination carboplatin and paclitaxel. We know that there are opportunities for us to incorporate bevacizumab as an antiangiogenic agent in the frontline setting, and there are data to support the incorporation of bevacizumab with carboplatin plus paclitaxel with respect to an improvement in progression-free survival. In this patient’s clinical scenario, where she had widely metastatic disease, involvement of the liver with suspected stage IVB disease, systemic treatment with carboplatin and paclitaxel, potentially incorporating bevacizumab, would be an appropriate therapeutic option.

There are different ways in which the chemotherapy can be considered. Most commonly, the carboplatin and the paclitaxel are now being given every 3 weeks [Q3 week] intravenously. There was obviously a period where there was a significant interest in intraperitoneal chemotherapy, and with the results of GOG-252 trial protocol, some have gone away from the intraperitoneal approach. There was also an excitement about weekly paclitaxel in combination with every-3-week carboplatin based on the Japanese GOG clinical trial, but again, based on the more recent ICON data, it suggests that the Q3-week regimen is equally effective with a reduction in treatment-related adverse events. In a patient such as this, the every-3-week regimen of carboplatin and paclitaxel, with or without bevacizumab, would be an appropriate intervention.

Whether or not a patient would be managed with primary surgery or neoadjuvant chemotherapy depends on multiple factors specifically related to stage, disease distribution, comorbidities, whether the patient would tolerate initial extensive surgery. The common denominator is that the intent of surgery is removal of all visible disease, and that plays a role in how we approach patients who have metastatic ovarian cancer when we make a decision about primary surgery versus neoadjuvant chemotherapy. For this patient’s scenario, neoadjuvant chemotherapy would have certainly been appropriate primary intervention as well, followed by interval cytoreduction.

The patient case scenario that we discussed specifically exemplified a primary resection with remaining gross residual disease. The patient had a 1.3-cm tumor of largest diameter remaining after primary resection. In patients of a suboptimal primary cytoreduction, one consideration would be to proceed with systemic therapy and potentially consider returning to the operating room after an interval of treatment, to re-explore the patient and resect the tumor. We’ve now more frequently gone away from that paradigm and we’ve proceeded with systemic chemotherapy, treating these patients again with cytotoxic or targeted approaches or enrollment on clinical trial, if one is open and a patient like this would be eligible for enrollment on a study such as this. But we’ve begun to move away from secondary cytoreduction or taking these patients back after chemotherapy to re-explore, because the therapeutic benefit of that intervention is unclear.

Transcript edited for clarity.

Case Overview:

Initial Presentation

• A 68-year-old postmenopausal woman presented with fatigue, urinary frequency, early satiety, abdominal bloating and distention
• PMH: HTN, medically treated with lisinopril
• SH: retired; grandmother of 3; never-smoker; social alcohol use
• PE: abdominal distention, bloating, and a positive fluid wave test; otherwise unremarkable

Clinical work-up

• Pelvic exam with transvaginal ultrasound showed a right ovarian mass
• Chest/abdomen/pelvis CT with contrast revealed a right adnexal 5.3-cm complex mass, a suspicious intraparenchymal liver lesion, retroperitoneal lymph node enlargement and concurrent pleural effusion
• Lymph node and adnexal mass biopsy confirmed high-grade, epithelial ovarian cancer; positive cytology of pleural effusion
  • T1N1M1
• Germline molecular testing showed BRCA1/2 wild-type, HRD+
• CA-125, 438 U/mL
• ECOG: 1

Treatment

• Patient underwent TAH/BSO, lymph node dissection, with suboptimal debulking; residual disease 1.3 cm
• Paclitaxel/carboplatin/bevacizumab + maintenance bevacizumab
  • After 3 cycles, patient underwent second debulking surgery, R0
• Continued on bevacizumab for 6 more cycles
  • Achieved partial response, post treatment CA-125, 40 U/mL
     

Follow-up

• At 3 months
  • CA-125, 18 U/mL
  • Chest/abdomen/pelvis CT showed no gross pelvic masses or nodes
  • Pelvic exam was unremarkable