Adding Bevacizumab to Chemotherapy Improves PFS in Endometrial Cancer

The addition of bevacizumab to carboplatin/paclitaxel chemotherapy significantly increases progression-free survival (PFS) in advanced/recurrent endometrial cancer. However, cardiovascular toxicity should be carefully evaluated in a population with pre-existing cardiovascular risk factors, according to the results of a randomized phase II trial (abstract 5502) presented at the American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.

“This is the first randomized trial suggesting efficacy of bevacizumab in advanced/recurrent endometrial cancer,” said Domenica Lorusso, MD, of the National Cancer Institute of Milan, Italy. “Expression of vascular endothelial growth factor (VEGF) in endometrial cancer has clinical and biological implications. Increased levels of VEGF are associated with higher histological grade, deeper myometrial invasion, nodal metastasis, and poorer outcome in endometrial cancer patients.”

Bevacizumab has been shown to be active in advanced/recurrent endometrial cancer in phase II trials as both a single agent and in combination with carboplatin and paclitaxel.

In this trial, researchers enrolled 108 endometrial cancer patients, with an average age of about 64 years, with advanced (stage III to IV) or recurrent (progression more than 6 months after completion of previous platinum chemotherapy) disease who had received up to one prior line of chemotherapy.

About two-thirds of the patients had recurrent disease, more than 20% had grade II tumors, and about 50% had grade III tumors. Almost half of the patients had hypertension.

The patients were randomized to receive standard doses of carboplatin/paclitaxel for 6 to 8 cycles (54 patients) with or without bevacizumab 15 mg/kg (54 patients) in combination and in maintenance until progression or unacceptable toxicity.

The patients received a median of 6 cycles of chemotherapy in both arms. Twice as many patients had dose delays for toxicity in the combination arm. More patients discontinued therapy due to progression in the chemotherapy-alone arm.

The results show that the study met the primary endpoint of PFS. After a median follow-up of 13 months, PFS favored the bevacizumab arm (13 months) over the chemotherapy-alone arm (8.7 months), as did the objective response rate (71.7% vs 54.3%). There was also a trend toward an overall survival advantage in the combination arm.

There were more treatment-related serious adverse events in the combination arm, but no difference in hematologic toxicity between the two arms. Neutropenia was slightly higher in the combination arm, and there were also more grade 2 hypertension, thrombotic events, and grade 2 or higher cardiac disorders. No new safety signals appeared.

In conclusion, Lorusso said, “These preliminary results suggest that the combination of carboplatin plus paclitaxel and bevacizumab significantly increased investigator-assessed PFS compared to chemotherapy alone in advanced/recurrent endometrial cancer. But particular attention should be paid to cardiovascular toxicity when using bevacizumab in the population of older patients with several comorbidities who have had previous chemotherapy.”

ASCO discussant Rebecca Kristeleit, MD, senior lecturer experimental therapeutics and consultant medical oncologist at the University College London, commented, “The benefit appears greatest in the group of patients with the greatest need. Carboplatin/paclitaxel plus bevacizumab is poised to become the new standard of care in advanced endometrial cancer. We await the outcome of an ongoing randomized phase III trial.”