Phase II Trial of Bevacizumab in the Treatment of Persistent or Recurrent Squamous Cell Carcinoma of the Cervix: A Gynecologic Oncology Group Study

Abstract

Purpose Vascular endothelial growth factor is a key promoter of tumor progression in cervical carcinoma. The Gynecologic Oncology Group (GOG) conducted a phase II trial to assess the efficacy and tolerability of bevacizumab, a recombinant humanized anti–vascular endothelial growth factor monoclonal antibody. Patients and Methods Eligible patients had recurrent cervical cancer, measurable disease, and GOG performance status ≤ 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 21 days until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and toxicity. Results Forty-six patients were enrolled (median age, 46 years); 38 patients (82.6%) received prior radiation as well as either one (n = 34, 73.9%) or two (n = 12, 26.1%) prior cytotoxic regimens for recurrent disease. Grade 3 or 4 adverse events at least possibly related to bevacizumab included hypertension (n = 7), thrombo-embolism (n = 5), GI (n = 4), anemia (n = 2), other cardiovascular (n = 2), vaginal bleeding (n = 1), neutropenia (n = 1), and fistula (n = 1). One grade 5 infection was observed. Eleven patients (23.9%; two-sided 90% CI, 14% to 37%) survived progression free for at least 6 months, and five patients (10.9%; two-sided 90% CI, 4% to 22%) had partial responses. The median response duration was 6.21 months (range, 2.83 to 8.28 months). The median PFS and overall survival times were 3.40 months (95% CI, 2.53 to 4.53 months) and 7.29 months (95% CI, 6.11 to 10.41 months), respectively. This compared favorably with historical phase II GOG trials in this setting. Conclusion Bevacizumab seems to be well tolerated and active in the second- and third-line treatment of patients with recurrent cervical cancer and merits phase III investigation.

Evaluation of the paclitaxel–ifosfamide–cisplatin (TIP) combination in relapsed and/or metastatic cervical cancer

“…A recent GOG study (GOG-204) -the largest phase III randomised trial in recurrent/metastatic cervical cancer -compared four platinum-based doublets with the reference arm of paclitaxelcisplatin, which was found to be not inferior to the three investigational arms (Monk et al, 2008). Moreover, another GOG phase II study (GOG-227C) of targeted anti-vascular therapy (bevacizumab 15 mg kg À1 ) in this patient population showed activity comparable with cytotoxics and was well tolerated (Monk et al, 2009).…”

Molecular targets for therapeutic interventions in human papillomavirus-related cancers (Review)

“…A strong association between higher VEGF expression in cervical cancer and worse prognosis has been observed (75,76).…”

Cytotoxic and Targeted Systemic Therapy in Advanced and Recurrent Cervical Cancer: Experience from Clinical Trials

“…Bevacizumab has been tested and used in several solid tumors with favorable results. The GOG performed a phase II trial to evaluate the efficacy and toxicity of bevacizumab (15 mg/kg every 3 weeks until disease progression or prohibitive toxicity) in persistent or recurrent squamous cell carcinoma of the cervix (Monk et al 2009a). Compared to historical control data from 6 GOG trials in this disease setting, bevacizumab showed remarkable activity.…”