In a study reported in the Journal of Clinical Oncology, Benoit You, MD, PhD, and colleagues found that an unfavorable CA-125 elimination rate constant K (KELIM) score, indicating poorer tumor chemosensitivity, was associated with derived benefit from first-line bevacizumab when given with chemotherapy to patients with ovarian cancer in the GOG-0128 trial.
As related by the investigators, a prior analysis conducted in the ICON-7 trial population showed that overall survival benefit with bevacizumab in the first-line setting in ovarian cancer was observed only in patients with high-risk disease and an unfavorable KELIM score. The current analysis sought to validate these findings.
Benoit You, MD, PhD
In GOG-0218, 1,873 patients received carboplatin/paclitaxel with concurrent–maintenance bevacizumab vs placebo. KELIM was assessable in 1,662 patients with three or more available CA-125 values. Outcomes were assessed according to favorable (≥ 1.0) and unfavorable (< 1.0) KELIM scores.
For patients treated with bevacizumab vs placebo, an unfavorable KELIM score was associated with a significant benefit in progression-free survival (median = 9.8 vs 6.1 months, hazard ratio [HR] = 0.70, 95% confidence interval [CI] = 0.59–0.82) and a numeric benefit in overall survival (median = 36.3 vs 31.8 months, HR = 0.87, 95% CI = 0.73–1.03). A favorable KELIM score was not associated with significant benefit in progression-free survival (median = 17.6 vs 13.6 months, HR = 0.96, 95% CI = 0.79–1.17) or benefit in overall survival (median = 55.7 vs 56.7 months, HR = 1.11, 95% CI = 0.89–1.39).
The greatest benefit of bevacizumab was observed among patients with high-risk disease (stage IV, or stage III operated with suboptimal debulking surgery) and an unfavorable KELIM score, with hazard ratios of 0.64 (95% CI = 0.53–0.78; median = 9.1 vs 5.6 months) for progression-free survival and 0.79 (95% CI = 0.65–0.97; median = 35.1 vs 29.1 months) for overall survival. No significant benefit was observed among patients with high-risk disease and a favorable KELIM score in either progression-free survival (median = 16.3 vs 11.7 months, HR = 0.88, 95% CI = 0.68–1.13) or overall survival (median = 59.6 vs 49.4 months, HR = 1.05, 95% CI = 0.79–1.39).
The investigators concluded, “This GOG-0218 trial investigation validates ICON-7 findings about the association between poor tumor chemosensitivity and benefit from concurrent-maintenance bevacizumab, suggesting that bevacizumab may mainly be effective in patients with poorly chemosensitive disease. Bevacizumab may be prioritized in patients with high-risk and poorly chemosensitive disease to improve their progression-free survival/overall survival (patient KELIM score calculator available on the Biomarker Kinetics website).”
Dr. You, of Centre Hospitalier Lyon-Sud, Lyon Investigational Center for Treatments in Oncology and Hematology, Lyon, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Université Claude Bernard Lyon 1 and by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.