GOG-0218 and ICON7 Trial Regimens as Maintenance Therapy

Ramez Eskander, MD: When we make a decision in the front line about incorporation of bevacizumab, both concurrent with chemotherapy and as a maintenance, we consider several factors. There have been a breadth of data suggesting a benefit specifically with respect to progression-free survival, with incorporation of bevacizumab concurrent with chemotherapy and continued as a maintenance. The 2 largest trials, in combination they accrued and enrolled over 3000 patients, GOG-0218 as well as ICON7, the European trial, looked at the incorporation of bevacizumab in patients with epithelial ovarian cancer. Importantly, the studies were slightly different. GOG-0218 was a 3-arm prospective and blinded clinical trial; ICON7 was a 2-arm study. ICON7 did also allow for enrollment of high-risk early stage disease, which GOG-0218 did not permit. GOG-0218 was limited to patients who had residual disease after resection if they had stage III ovarian cancer, and any patient with stage IV ovarian cancer.

Most importantly, the data from both studies were quite robust in showing a preserved progression-free survival benefit, and a hazard ratio of approximately 0.7 in those patient populations when you incorporate bevacizumab with chemotherapy and use it as a maintenance. This progression-free survival advantage certainly needs to be balanced against potential adverse events, and we do know that bevacizumab is associated with a unique adverse event profile when compared to cytotoxic chemotherapy, specifically hypertension, proteinuria, possibly perforation, blood clots. So we make that determination as we discuss treatment options with patients when we balance the potential benefit, specifically here with the progression-free survival advantage, versus adverse effects.

There was also a follow-up study looking at overall survival in GOG-0218 that was published by Krishnansu Tewari, MD. And I think the important message here is both ICON7 and GOG-0218, when you looked at those high-risk patients, patients who had suboptimal resections for stage III disease, bulky residual disease, or stage IV disease, that patient population appeared to benefit the most with the incorporation of bevacizumab and bevacizumab maintenance. For GOG-0218, in the updated data, it was almost a 10-month difference, approaching or meeting statistical significance. So in these high-risk patients, who look like they have bulky disease, consideration in incorporating bevacizumab into the treatment paradigm may be appropriate.

The duration of bevacizumab use is tailored in clinical practice quite frequently. Each of the prior clinical trials defined an interval of time in which patients would receive bevacizumab as a maintenance, following completion of the combination phase of chemotherapy plus bevacizumab. In GOG-0218, those patients were treated for approximately 15 cycles after completion of the combination phase. It was slightly shorter in the ICON7 trial. In a follow-up study, Amit Oza, MD, and colleagues reported that bevacizumab duration could be safely extended, which appeared to result in longer progression-free survival. Importantly, this was a study, the ROSiA study, but it was a single-arm study exploring this question, which makes interpretation of the results slightly more difficult. Nonetheless, it did suggest that patients could be treated for a longer period safety, without significant adverse events, tolerating treatment and seeing a progression-free survival advantage. In clinical practice, I frequently hear that providers keep patients on it as long as they’re tolerating treatment, and maintain the bevacizumab while patients show no evidence of progression or unacceptable toxicity.

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