Adjuvant Chemotherapy + Bevacizumab for Ovarian Cancer

Shannon Westin, MD: Hello, everyone, and welcome to this Targeted Oncology™ ovarian cancer Virtual Tumor Board®. We’re excited to have you. I’ve got 2 wonderful people here with me. We’re excited to talk to you a little about ovarian cancer, especially management in line of all the new approvals that we’ve seen over the last few months. Thank you so much for joining us. We’re going to be focused today on advanced ovarian cancer. In today’s presentation, my colleagues and I will review 3 clinical cases. We will discuss an individualized approach to treatment for each patient, and we’ll review key clinical trial data that impact our decisions.

I am Dr Shannon Westin from The University of Texas MD Anderson Cancer Center, in Houston, Texas. Today I’m joined by my colleagues Dr Thomas Krivak from the Allegheny Health Network in Pennsylvania.

Thomas C. Krivak, MD: Hello.

Shannon Westin, MD: And Dr Chad Hamilton from the Inova Schar Cancer Institute in Virginia.

Chad Hamilton, MD: Hi there. Very glad to be here.

Shannon Westin, MD: Welcome. Thank you for joining us. Before we get started on our first case, I’d like to discuss several additions to the NCCN [National Comprehensive Cancer Network] Guidelines along with new FDA approvals.

I’m fortunate to be able to talk a little about what things have changed in primary therapy for advanced ovarian cancer, and over the last few weeks, we’ve had a number of exciting approvals. I’m going to take a few minutes to review what we know about the treatment of patients with up-front ovarian cancer, specifically focusing on maintenance strategies, which is exciting to be able to do.

First, let’s go back in time a little to GOG-0218. Many of us are familiar with these data looking at the addition of bevacizumab to adjuvant chemotherapy. This was a randomized, 3-arm trial, where 1 arm received just standard paclitaxel-carboplatin chemotherapy; the next arm had this chemotherapy in addition to bevacizumab, followed by a placebo maintenance; and then the third arm had the combination of chemotherapy with bevacizumab, followed by bevacizumab maintenance. The primary end point for this study was progression-free survival, and of note, the patients received 15 months of bevacizumab as a maintenance.

As we remember, the progression-free survival difference was predominantly between the patient population that had bevacizumab throughout: bevacizumab with chemotherapy, followed by bevacizumab maintenance. It was a reduction in the risk of progression of about 30% with an absolute difference in about 3 to 4 months, depending how you were identifying progression, but there was no difference with overall survival. There have been some interesting subset analyses that indicate, perhaps in a patient population that is stage IV disease, that this can potentially provide some overall survival benefit, but you have to be cautious whenever you’re looking at these post hoc subset analyses.

We are about to talk about a number of different indications with PARP inhibition, so it’s important to look at biomarkers for PARP inhibition in regard to the findings from GOG-0218 and the efficacy of bevacizumab. There were slightly better outcomes with those patient populations that had a BRCA mutation or were known to have some aberration that led to homologous recombination deficiency overall. When you look at progression-free survival, it didn’t seem that the bevacizumab arms were favored when you look at those forest plots below. It is leaning more toward favoring control in the positive biomarkers, but these are not statistically significant findings.

Then we always have to talk if we’re adding something to chemotherapy, if we’re adding a maintenance, what are the [adverse] effects, what are the adverse events? The No. 1 concern is GI [gastrointestinal] events. We worry about perforation and dangerous events, and overall they found that those were increased in the bevacizumab groups but not by too much. A majority of the patients for whom the biggest adverse events were found was hypertension and some proteinuria, but we’ve all gotten comfortable with managing these. Adverse events are generally not an issue if you’re deciding whether to use this agent.

Transcript edited for clarity.