Continuous anti-angiogenic therapy after tumor progression in patients with recurrent high-grade epithelial ovarian cancer: phase I trial experience

Abstract

High-grade epithelial ovarian cancer (HG-EOC) is the most lethal gynecologic malignancy worldwide Once patients develop chemoresistance, effective novel strategies are required to improve prognosis We analyzed characteristics and outcomes of 242 consecutive patients with HG-EOC participating in 94 phase I clinical trials at The University of Texas MD Anderson Cancer Center. Baseline lactate dehydrogenase levels, albumin levels, and number of metastatic sites were independent predictors of overall survival (OS). Receiving more than 1 phase I protocol was associated with improved OS (p < 0.001). Regimens including a chemotherapeutic agent plus bevacizumab or Aurora A kinase inhibitor led to a median progression-free survival (PFS) duration of more than 6 months. Although patients receiving bevacizumab-based regimens in the phase I clinical trials had significantly longer PFS than those receiving other anti-angiogenic therapies (p = 0.017), patients treated with vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) had significantly longer OS (12.2 months) than those not treated with VEGFR-TKIs (8.6 months, p = 0.015).In conclusion, anti-angiogenic therapy is one of the most important strategies for the treatment of HG-EOC, even in those who have already experienced tumor progression. Therefore, eligible patients with HG-EOC should be encouraged to participate in novel phase I studies of anti-angiogenic therapies, even after disease progression.

Keywords: anti-angiogenesis; epithelial ovarian cancer; overall survival; progression-free survival; tumor progression.

Figure 1. Waterfall plot shows the best objective responses according to Response Evaluation Criteria in Solid Tumors (RECIST)

All 358 phase I clinical trial therapies administered to 242 patients are shown. A 21% or higher RECIST response represents new lesions, early tumor progression, or early withdrawal from treatment for other reasons; this may be arbitrarily designated 21% or higher disease progression or actual tumor progression of 21% or higher. VEGFR-TKI, vascular endothelial growth factor receptor-tyrosine kinase inhibitor.

Figure 2. Kaplan-Meier plot shows progression-free survival (PFS) after phase I therapies (358 phase I clinical trial therapies) administered to 242 patients with recurrent high-grade epithelial ovarian cancer according to the type of therapy

VEGFR-TKI, vascular endothelial growth factor receptor-tyrosine kinase inhibitor.

Figure 3

Kaplan-Meier plots shows overall survival (OS) in patients with recurrent high-grade epithelial ovarian cancer (n = 242) according to A. the number of therapies received in phase I clinical trials and B. the type of therapy received (vascular endothelial growth factor receptor-tyrosine kinase inhibitor [VEGFR-TKI]-based therapy or other).