Serum CA19-9 Response Is an Early Predictive Marker of Efficacy of Regorafenib in Refractory Metastatic Colorectal Cancer

Abstract

Purpose: Regorafenib improves survival in chemorefractory metastatic colorectal cancer (mCRC) patients. However, regorafenib induces various adverse events (AEs) that often impair patients' quality of life. Identification of early predictive markers of the efficacy is warranted. Methods: We retrospectively examined 146 consecutive mCRC patients who received regorafenib. Clinical parameters, including patient background, AEs, and changes in biochemical parameters until day 28, were evaluated to identify efficacy predictors. Results: Median progression-free survival (PFS) was 2.1 months, and median overall survival was 6.6 months. Major AEs in all cycles were hand-foot skin reaction, hypertension, and increased aspartate transaminase. We extracted 121 patients for prognostic analysis. In univariate analysis, decreased carcinoembryonic antigen (HR: 0.570, p = 0.012) and decreased carbohydrate antigen 19-9 (CA19-9) (HR: 0.422, p = 0.0012) were identified as prognostic markers of PFS. Patients in whom serum CA19-9 decreased after regorafenib exhibited significantly better PFS (median 3.7 vs. 2.0 months, p = 0.004) than those in whom serum CA19-9 did not decrease. Multivariate analysis revealed early CA19-9 decrease as an independent predictive factor (HR: 0.415, 95% CI: 0.210-0.818, p = 0.011). Conclusion: Early response of CA19-9 may predict the efficacy of regorafenib. Additional studies are needed for external validation.

Apatinib Monotherapy for Chemotherapy-Refractory Metastatic Colorectal Cancer: A Multi-centre, Single-Arm, Prospective Study

“…The association of CA19-9 with the efficacy of apatinib has not been reported but there is evidence in similar biomarker studies of other anti-angiogenic agents. Levels of or changes in CA19-9 have been reported to predict the efficacy of bevacizumab or bevacizumab-containing chemotherapy and regorafenib in mCRC in some previous studies [55][56][57] . We have suggested two possible reasons why CA19-9 rather than CEA was an early predictive factor in our study.…”

Evolution of regorafenib from bench to bedside in colorectal cancer: Is it an attractive option or merely a “me too” drug?

“…A retrospective study of 121 mCRC patients treated with regorafenib evaluated the role of serum biochemical parameters such as carcinoembryonic antigen and carbohydrate antigen 19-9 (CA 19-9) as predictive biomarkers. 52 In both univariate and multivariate analyses, early CA 19-9 decrease was identified as an independent predictive factor of response to regorafenib therapy. These results require further validation using external data sets prior to clinical use.…”

Treatment Outcomes of Metastatic Colorectal Cancer Patients Treated with Regorafenib as Third-Line Setting-A Multicenter Study

“…Indeed, there is no predictive biomarker to allow the selection of patients most likely to benefit from regorafenib (11). However, Komori et al (15) reported that serum CA19-9 response was an early predictive marker of efficacy of regorafenib in mCRC.…”