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
Study Details
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.
Key Findings
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.
