Hematologic Toxicity Assessment In Solid Tumor Patients Treated With Cetuximab: A Pooled Analysis Of 18 Randomized Controlled Trials

The role of cetuximab in treatment-related hematologic toxicity is not clear. We performed a meta-analysis of published randomized controlled trials (RCTs) to determine the overall risk of grade 3 hematologic toxicity events (HTEs) associated with cetuximab. PubMed, EMBASE, and Web of Knowledge databases as well as abstracts presented at American Society of Clinical Oncology conferences and were searched to identify relevant studies. Eligible studies included RCTs in which cetuximab in combination with chemotherapy or chemoradiotherapy was compared with chemotherapy or chemoradiotherapy alone. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects models. A total of 11,234 patients with a variety of advanced solid tumors from 18 RCTs were included in the meta-analysis. Compared with chemotherapy alone, the addition of cetuximab was associated with increased risks of grade 3 leucopenia/neutropenia and anemia events in colorectal cancer, with RRs of 1.16 (95% CI 1.05-1.27, p=0.002; incidence, 21.0 vs. 18.0%) and 2.67 (95% CI 1.53-4.65, p=0.01; incidence, 4.0 vs. 2.0%), respectively. Cetuximab was also associated with an increased risk of leucopenia/neutropenia in nonsmall cell lung cancer (NSCLC) (RR: 1.15; 95% CI 1.08-1.22, p<0.01). Additionally, K-ras wild type in the case of colorectal cancer patients was more vulnerable to grade 3 leucopenia or neutropenia events in cetuximab group (RR: 1.31; 95% CI 1.11-1.54, p=0.001). With present evidence, cetuximab in conjunction with chemotherapy or chemoradiotherapy, compared with chemotherapy or chemoradiotherapy alone, was associated with increased slight risk of grade 3 HTEs, especially in colorectal cancer and NSCLC.What's new? Cetuximab, an anti-EGFR monoclonal antibody (mAb), is used in combination with chemotherapy for several types of cancer. While many studies evaluating the toxicity of mAbs have focused on fatal adverse events, less severe toxic effects can still have a major impact on patient health. In this meta-analysis, the authors found that there is a slight but significant increase in the risk of severe hematologic toxicity associated with cetuximab treatment. Rigorous hematological monitoring of a patient's peripheral hemogram is therefore warranted when cetuximab is part of a treatment regimen.