Previously published reports from the randomized phase III Gynecologic Oncology Group (GOG) protocol 240 clinical trial showed that adding bevacizumab (Avastin) to a chemotherapy regimen of paclitaxel plus cisplatin or topotecan significantly increased overall survival and progression-free survival in women with advanced cervical cancer. The study’s findings led to approval of bevacizumab in combination with chemotherapy in the treatment of advanced cervical cancer by the U.S. Food and Drug Administration in 2014.
A second major objective of the GOG 240 study was to assess the validity of the Moore clinical prognostic factor scoring system as a tool to identify patients with advanced cervical cancer who may not benefit from the addition of bevacizumab to systemic chemotherapy. The study found that patients who were at intermediate and high risk of poor outcome gained survival benefit by almost 6 months—from 12.1 to 17.9 months for those in the intermediate-risk category and from 6.3 to 12.1 months for those in the high-risk category. However, for patients in the low-risk Moore category, there was not a statistically significant difference in median overall survival among those assigned chemotherapy alone and those assigned chemotherapy and bevacizumab (21.8 vs 22.9 months). The study by Tewari et al was published in Clinical Cancer Research.
The researchers examined the five Moore clinical risk factors for prognostic value with clinical outcome variables (overall survival, progression-free survival, and response rate). The variables examined were race (African ancestry or not), performance status (1 or 0), measurable disease in the pelvis (yes/no), prior platinum as a radiation sensitizer (yes/no), and progression-free interval from the diagnosis of disease (< 365 days or ≥ 365 days).
Risk categories included low risk (0–1 factor), mid risk (2–3 factors), and high risk (4–5 factors). Each test of association was conducted at the 5% level of significance. Logistic regression and survival analysis was used to determine whether factors were prognostic or could be used to guide therapy.
For the entire population (N = 452), high-risk patients had significantly worse overall survival (P < .0001). The hazard ratios of death for treating with topotecan in low-risk, mid-risk, and high-risk subsets were 1.18 [95% confidence interval (CI) = 0.63–2.24], 1.11 (95% CI = 0.82–1.5), and 0.84 (95% CI = 0.50–1.42), respectively. The hazard ratios of death for treating with bevacizumab in low-risk, mid-risk, and high-risk subsets were 0.96 (95% CI = 0.51–1.83; P = .9087), 0.673 (95% CI = 0.5–0.91; P = .0094), and 0.536 (95% CI = 0.32–0.905; P = .0196), respectively.
“Our study prospectively validates the Moore criteria as prognostic for outcome among patients with advanced cervical cancer and identifies a population, those at low risk for poor outcome, who are unlikely to gain benefit from treatment with bevacizumab,” said Krishnansu S. Tewari, MD, Professor and Director of Research in the Division of Gynecologic Oncology at the University of California, Irvine, and first author of the study, in a statement. “Therefore, the Moore criteria represent the first prospectively validated scoring system in cervical cancer. They provide oncologists with a clinical instrument to help them counsel patients and their families regarding anticipated outcomes and the potential benefit, or lack of benefit, of adding the recently approved cervical cancer drug, bevacizumab, to standard chemotherapy.”
Krishnansu S.Tewari, MD, is the corresponding author of this study, which was funded by the National Cancer Institute.
Dr. Tewari is a consultant/advisory board member for Genentech/Roche. Bradley J. Monk reported receiving a commercial research grant from Genentech, speakers’ bureau honoraria from Roche/Genentech, and is a consultant/advisory board member for Roche/Genentech. Richard T. Penson reported receiving a commercial research grant from Roche and is a consultant/advisory board member for Roche. No potential conflicts of interest were disclosed by the other authors.
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