Bevacizumab combination improves PFS in advanced, recurrent endometrial cancer

Issue: July 10, 2015

CHICAGO — The addition of bevacizumab to the combination of carboplatin and paclitaxel significantly increased PFS for patients with advanced-stage or recurrent endometrial cancer, according to a phase 2 study presented at the ASCO Annual Meeting.

Perspective from Kunle Odunsi, MD, PhD, FRCOG, FACOG

Although the prognosis for advanced or recurrent endometrial cancer is poor, bevacizumab (Avastin, Genentech) has previously shown activity in advanced or recurrent endometrial cancer, according to study background. Data have indicated response rates range from 13% to 22% and 6-month disease control is approximately 40% with bevacizumab.

Domenica Lorusso, MD, a researcher with the National Cancer Institute of Milan in Italy, and colleagues conducted this randomized phase 2 trial to compare carboplatin and paclitaxel alone — the standard treatment in this setting — with a combination of those agents plus bevacizumab.

PFS served as the study’s primary endpoint.

Between 2012 and 2014, the researchers randomly assigned 108 patients with advanced or recurrent endometrial cancer to carboplatin and paclitaxel alone (n = 54) or with bevacizumab (n = 54). All patients received the standard dose of carboplatin and paclitaxel for 6 to 8 cycles. Those assigned additional bevacizumab received 15-mg/kg doses during the combination phase and as maintenance until the disease progressed or there was an unacceptable toxicity.

Median follow-up was 13 months as of March 2015.

The overall response rate was 72.7% (95% CI, 59.5-85.9) in the bevacizumab arm compared with 54.3% (95% CI, 39.9-68.7) in the carboplatin–paclitaxel alone arm.

There were 31 PFS events in the carboplatin–paclitaxel alone arm vs. 27 in the bevacizumab arm. The HR for PFS in favor of the bevacizumab combination was 0.57 (95% CI, 0.34-0.96).

Median PFS was 8.7 months (95% CI, 6.3-11.2) in the standard therapy arm and 13 months (95% CI, 9.2-16.8) in the bevacizumab arm.

Four patients assigned bevacizumab experienced grade 3 cardiac toxicities vs. zero patients in the standard treatment group.

Overall, eight patients experienced 13 serious adverse events. Those events included three instances of deep vein thrombosis, three incidences of retinal artery thrombosis, two cases of intracardiac thrombus as well as one silent myocardial infraction and one cerebrovascular accident.

“The addition of bevacizumab to carboplatin and paclitaxel significantly increased PFS in recurrent endometrial cancer,” Lorusso said during her presentation. “However, cardiovascular toxicity should still be carefully evaluated in a population with pre-existing cardiovascular risk factors before taking bevacizumab.” – by Anthony SanFilippo

Reference: Lorusso D, et al. Abstract 5502. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosure: Lorusso reports honoraria and research funding from and consultant/advisory roles with Amgen, AstraZeneca, Janssen-Cilag, PharMar and Roche. Please see the abstract for a list of all other researchers’ relevant financial disclosures.

Perspective

Kunle Odunsi, MD, PhD, FRCOG, FACOG

This study is actually one of the few studies that have tried to identify novel targeted agents for advanced endometrial cancers. Endometrial cancers lag behind in terms of clinical investigation of novel agents. Part of the reason for that is because a majority of the patients present with stage I, disease which is potentially curable. But for those patients who present with advanced, metastatic or recurrent disease, the options for them are very limited. Putting things in perspective this is a very important study. Basically, what investigators have done is to take the current standard chemotherapy for endometrial cancer — which is a combination of carboplatin and paclitaxel — and ask the question, “If we add an anti-angiogenic agent bevacizumab, do we see increased benefit for patients?” So, this was actually a fairly well-designed, randomized phase 2 study whereby they were able to meet their primary endpoint of PFS. There was a PFS benefit of 4.3 months, which is very striking. However, the data is not mature enough to comment on OS. But, the strength of the study is the fact that it has a very good design and they were able to do imaging studies. I like the way Lorusso described it when she called it “symmetric imaging studies.” Patients on both the experimental and control arms received imaging studies at approximately the same time, which were comparable. Another strength was the relatively homogenous population of patients in the trial. There was a histologic stratification of subjects. All of those actually helped to raise the level of the study. Because we don’t have OS data and it’s a randomized phase 2 trial, we still need a larger phase 3 trial to clearly define the role of bevacizumab. Still, these data are very promising.

Kunle Odunsi, MD, PhD, FRCOG, FACOG

Roswell Park Cancer Institute

Disclosures: Odunsi reports no relevant financial disclosures.