Baseline serum lactate dehydrogenase level predicts survival benefit in patients with metastatic colorectal cancer receiving bevacizumab as first-line chemotherapy: a systematic review and meta-analysis of 7 studies and 1,219 patients

Wanjing Feng, Yue Wang, Xiaodong Zhu


Background: Bevacizumab, a humanized monoclonal antibody against vascular epithelial growth factor, plays a significant role in first-line, second-line, beyond-progression, and maintenance treatment of patients with metastatic colorectal carcinoma (mCRC). Nevertheless, there are currently no biomarkers available to predict patient response or resistance to bevacizumab, which would be useful in clinical trials.
Methods: Using PRISMA guidelines, we conducted a systematic review and meta-analysis of the association between serum lactate dehydrogenase (LDH) level and progression-free survival (PFS), overall survival (OS), and objective response rate in mCRC patients treated with bevacizumab-based first-line chemotherapy. A comprehensive, computerized literature search of PubMed, the Web of Science, Scopus, Ovid, and the gray literature was performed. Only studies conforming to specific eligibility criteria were included. Pooled hazard ratios (HRs) were estimated using random-effects or fixed-effects models according to heterogeneity between studies. Sensitivity analysis was conducted to evaluate the stability of the results by removing each individual study from the meta-analysis.
Results: Seven eligible studies of 1,219 total patients were included in the analysis. Meta-analysis of all studies revealed that high serum LDH level is associated with shorter PFS (HR: 1.43, 95% CI: 1.05–1.94; P=0.023) and OS (HR: 1.667, 95% CI: 1.230–2.259; P=0.001) times in mCRC patients treated with bevacizumab-based first-line chemotherapy. However, there was no significant association between serum LDH and objective response rate.
Conclusions: High serum LDH level is significantly associated with shorter PFS and OS time and may have utility as a prognostic factor for mCRC patients receiving bevacizumab as first-line chemotherapy and as a predictive factor for those receiving bevacizumab-based therapy at other times.