Hematologic toxicity assessment in solid tumor patients treated with cetuximab: a pooled analysis of 18 randomized controlled trials

Abstract

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 ClinicalTrials.gov 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.

Keywords: cetuximab; chemotherapy; hematologic toxicity; meta-analysis.