Western Regional Blog – BC, YK, AB, NWT and Nunavut
Abstract: N Engl J Med. 2014;370(8):734-743.
Results of the Gynecologic Oncology Group (GOG) Trial 240 showed that the addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer significantly improved median OS by 3.7 months compared with chemotherapy alone (17.0 months versus 13.3 months; HR = 0.71; P = .004).
This phase III trial enrolled 452 patients who were randomized to chemotherapy with or without bevacizumab (15 mg/kg). Chemotherapy consisted of cisplatin (50 mg/m2) plus paclitaxel (135 mg/m2 or 175 mg/m2) or topotecan (0.75 mg/m2 on days 1 to 3) plus paclitaxel (175 mg/m2 on day 1) every 21 days until disease progression, unacceptable toxicity, or a complete response.
Of note, topotecan plus paclitaxel was not superior to cisplatin plus paclitaxel (HR for death = 1.20) even among patients with prior exposure to cisplatin (70% of patients in both arms had received prior platinum-based chemoradiotherapy).
Addition of bevacizumab also significantly improved PFS (median 8.2 months vs 5.9 months; HR = 0.67; P = .002) and ORR (48% vs 36%; P = .008) but increased the incidence of grade ≥2 hypertension (25% vs 2%), grade ≥3 thromboembolic events (8% vs 1%), and grade ≥3 gastrointestinal fistulas (3% vs 0%).
The authors characterized the OS benefit as clinically meaningful and concluded that these results provide support for further investigation of antiangiogenic therapy in patients with other HPV-induced tumors, including vulvar, anal, penile, and oropharyngeal carcinomas.
Improved survival with bevacizumab in advanced cervical cancer.
Tewari KS1, Sill MW, Long HJ 3rd, Penson RT, Huang H, Ramondetta LM, Landrum LM, Oaknin A, Reid TJ, Leitao MM, Michael HE, Monk BJ.
BACKGROUND: Vascular endothelial growth factor (VEGF) promotes angiogenesis, a mediator of disease progression in cervical cancer. Bevacizumab, a humanized anti-VEGF monoclonal antibody, has single-agent activity in previously treated, recurrent disease. Most patients in whom recurrent cervical cancer develops have previously received cisplatin with radiation therapy, which reduces the effectiveness of cisplatin at the time of recurrence. We evaluated the effectiveness of bevacizumab and nonplatinum combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer.
METHODS: Using a 2-by-2 factorial design, we randomly assigned 452 patients to chemotherapy with or without bevacizumab at a dose of 15 mg per kilogram of body weight. Chemotherapy consisted of cisplatin at a dose of 50 mg per square meter of body-surface area, plus paclitaxel at a dose of 135 or 175 mg per square meter or topotecan at a dose of 0.75 mg per square meter on days 1 to 3, plus paclitaxel at a dose of 175 mg per square meter on day 1. Cycles were repeated every 21 days until disease progression, the development of unacceptable toxic effects, or a complete response was documented. The primary end point was overall survival; a reduction of 30% in the hazard ratio for death was considered clinically important. 22
RESULTS: Groups were well balanced with respect to age, histologic findings, performance status, previous use or nonuse of a radiosensitizing platinum agent, and disease status. Topotecan-paclitaxel was not superior to cisplatin-paclitaxel (hazard ratio for death, 1.20). With the data for the two chemotherapy regimens combined, the addition of bevacizumab to chemotherapy was associated with increased overall survival (17.0 months vs. 13.3 months; hazard ratio for death, 0.71; 98% confidence interval, 0.54 to 0.95; P=0.004 in a one-sided test) and higher response rates (48% vs. 36%, P=0.008). Bevacizumab, as compared with chemotherapy alone, was associated with an increased incidence of hypertension of grade 2 or higher (25% vs. 2%), thromboembolic events of grade 3 or higher (8% vs. 1%), and gastrointestinal fistulas of grade 3 or higher (3% vs. 0%).
CONCLUSIONS: The addition of bevacizumab to combination chemotherapy in patients with recurrent, persistent, or metastatic cervical cancer was associated with an improvement of 3.7 months in median overall survival. (Funded by the National Cancer Institute; GOG 240 ClinicalTrials.gov number, NCT00803062.).