Title: Anti-Angiogenic treatment of cervical cancer: Significant tumor regression with severe toxicity
Abstract: Objectives: Anti–vascular endothelial growth factor monoclonal antibodies inhibit tumor angiogenesis, consequently impeding the recruitment of new vasculature to existing and new tumor lesions. The addition of bevacizumab (BEV) to combination chemotherapy in patients with recurrent cervical cancer results in significant improvement in median overall survival. We sought to compare the patterns of disease progression and toxicity in women with recurrent cervical cancer after receiving BEV versus non-BEV combination chemotherapy. Methods: A single-institution retrospective chart review was conducted of women with recurrent and metastatic cervical cancer who were treated with salvage chemotherapy with or without BEV between 2005 and 2015. All patients were on first- or second-line salvage treatment. Demographics and clinicopathologic data were obtained. Disease progression was defined by RECIST criteria. Reasons for treatment discontinuation were also recorded. Statistical analysis was performed using the Fisher exact test and Kaplan-Meier survival analysis. Results: Seventy-four patients were identified. Twenty-nine patients were treated with BEV + chemotherapy and 45 patients with chemotherapy alone. Disease progression solely attributed to increase in existing target lesions was 7% in the BEV + chemotherapy group versus 27% for the chemotherapy group (P = .04). New target lesions were identified in 3% of the BEV + chemotherapy group compared with 38% of chemotherapy group (P = .0006). Interestingly, the patient who experienced a progression to new disease in the BEV + chemotherapy group had acquired immunodeficiency syndrome. Cessation of treatment secondary to severe toxicities was seen in 48% of the BEV + chemotherapy compared with 13% of the chemotherapy group (P = .001). About 24% of patients who were receiving BEV and stopped for toxicities were because of fistula formations. The progression-free survival was significant (P = .0001) and the overall survival showed a trend toward significance (P = .07). However, no significant difference in survival was seen between the 2 groups after disease progression (P = .8). Conclusions: Antiangiogenic treatment of recurrent cervical cancer significantly decreases progression by inhibiting growth of both existing and new disease. Toxicity is a major reason for cessation of antiangiogenic treatment. Yet, no survival advantage is seen after progression on antiangiogenic therapy.