Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study

Abstract

Purpose: Bevacizumab, a recombinant humanized monoclonal antibody against vascular endothelial growth factor-A (VEGF-A), has clinical activity in multiple tumor types. We conducted a phase II trial to assess the activity and tolerability of single-agent bevacizumab in recurrent or persistent endometrial cancer (EMC).

Patients and methods: Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status of ≤ 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression or prohibitive toxicity. VEGF-A was assessed by immunohistochemistry in archival tumor and by enzyme-linked immunosorbent assay in pretreatment plasma. Primary end points were progression-free survival (PFS) at 6 months and overall response rate.

Results: Fifty-six patients were enrolled. Fifty-two patients were eligible and evaluable. Median age was 62 years, and prior treatment consisted of one or two regimens in 33 (63.5%) and 19 (36.5%) patients, respectively. Twenty-nine patients (55.8%) received prior radiation. Adverse events were consistent with those expected with bevacizumab treatment. No GI perforations or fistulae were seen. Seven patients (13.5%) experienced clinical responses (one complete response and six partial responses; median response duration, 6.0 months), and 21 patients (40.4%) survived progression free for at least 6 months. Median PFS and overall survival times were 4.2 and 10.5 months, respectively. Suggested associations were observed between high VEGF-A and adjusted hazard of death or tumor response when evaluated in tumor/plasma or plasma, respectively.

Conclusion: Bevacizumab is well tolerated and active based on PFS at 6 months in recurrent or persistent EMC and warrants further investigation.

Fig 1.

Kaplan-Meier plots demonstrating overall survival (OS) and progression-free survival (PFS) for the 52 patients in the study population.

Fig 2.

(A) Scatter plot for vascular endothelial growth factor-A (VEGF-A) concentration in pretreatment plasma in picograms per milliliter by clinical tumor response classified as progressive disease (PD), stable disease (SD), and partial response (PR)/complete response (CR). (B) Kaplan-Meier estimates of progression-free survival by pretreatment plasma VEGF-A categorized at the median as low (< 76.9 pg/mL) versus high (≥ 76.9 pg/mL). (C) Kaplan-Meier estimates of overall survival by pretreatment plasma VEGF-A categorized at the median as low (< 76.9 pg/mL) versus high (≥ 76.9 pg/mL).