Frontline Bevacizumab Strategies in Ovarian Cancer

David O’Malley, MD:When we look at patients regarding upfront treatment and the utilization of bevacizumab, it’s very important to look at the 2 largest trials, which are GOG-218 and ICON7. Both of these trials were positive for progression-free survival. When we look at the treatment options for these patients, there was a subgroup analysis in ICON7 that identified a higher-risk patient population: those going on neoadjuvant therapy or those with stage 4 disease, which this patient had, because her thoracentesis was positive for adenocarcinoma.

When looking at those patients, they seemed to benefit the most. Now, this is a subgroup analysis in ICON7. When we looked at those data in a post hoc analysis of GOG-218, the results were not as straightforward. But in looking at patients who I’m going to utilize bevacizumab for, a patient with a large volume of ascites, which bevacizumab has clearly shown to help dry up, would really come into my thought process.

The FDA is currently reviewing the use of bevacizumab in the up-front setting. We expect that it will be approved. If it is approved in the up-front setting, we will see more patients receiving it, and having the option of treatment in patients who were previously untreated will be a benefit. Which patients are going to maximally benefit, and where am I going to utilize it? Some practitioners will use it with all patients. In my practice, we look to use bevacizumab in the up-front setting for patients who have stage 4 disease, who potentially required neoadjuvant chemotherapy, who have large-volume disease at the end of their primary debulking, or who are extremely symptomatic secondary to their ascites or pleural effusions.

With regard to dosing, ICON7 used 7.5 mg/kg every 3 weeks, while most trials have utilized 15 mg/kg. The current approval in the United States is for 15 mg/kg in the platinum-sensitive setting, and we suspect the upfront dosing will be the same. In the United States, I would recommend using 15 mg/kg, because that’s where most of the data lie. Are there other treatment options? Of course. Bevacizumab has a very long half-life, and there are different ways to modify it, but I would stay away from that and use the doses that have been studied.

This patient had a complete response to up-front therapy and was continued on bevacizumab maintenance. Many of our patients will have a complete response—as high as 80% of them. Now, how do you break that up regarding the differences between those with high-volume disease or neoadjuvant therapy? There’s probably some wiggle room there.

But when a patient walks into our office with advanced ovarian cancer, our goal from the moment I meet them is to have a complete response: to get them to no clinical evidence of disease and into remission. We know that a very high percentage of these advanced-stage—stage 4 and bulky upper-abdominal stage 3c—patients will recur by at least 80%. With those patients, we have to have our thought process on what are we going to utilize in the future. But really, I put all my effort into that first treatment option and go over those agents available to them, which are carboplatin/paclitaxel with or without bevacizumab.

Transcript edited for clarity.

Case: A 69-year-old Woman with Advanced Serous Ovarian Cancer

January 2017

• A 69-year-old Caucasian woman presented to the emergency department with shortness of breath
• PMH: mild HTN and DM, medically managed; morbid obesity
• PE: large volume ascites
• CT angiography (chest) showed large bilateral pulmonary effusions, no pulmonary thromboembolism
• Laboratory findings remarkable for CA 125, 525U/mL
• Thoracentesis (1500 cc); cytology showed high grade adenocarcinoma
• Paracentesis (4500 cc); cytology showed high grade adenocarcinoma
• Core biopsy of omentum; high grade serous carcinoma; p53 (+)/ PAX 8 (+) /WTI and CX 7 (+); BRCA1/2 wild-type
• The patient underwent debulking surgery with incomplete cytoreduction
• She was treated as part of a clinical trial with carboplatin/paclitaxel + bevacizumab followed by continuous bevacizumab maintenance

April 2018

• Fifteen months later, the patients complained of severe abdominal bloating and fatigue
• Imaging showed multifocal recurrence within the abdominal cavity
  • CA 125, 322 U/mL
  • ECOG 1
• She was started on carboplatin/docetaxel
• After 6 cycles of therapy she had a partial response to therapy with bulky residual disease
• She was initiated on rucaparib maintenance therapy, 600 mg BID
• Hb fell to 7.2 g/dl, managed with treatment interruption and then dose reduction to rucaparib 500 mg