Radiotherapy and Receptor Tyrosine Kinase Inhibition for Solid Cancers (ROCKIT): a Meta-Analysis of 13 Studies

Background We hypothesized that the addition of receptor tyrosine kinase inhibitors (RTKis, e.g., lapatinib, erlotinib, cetuximab, bevacizumab, panitumumab) to radiotherapy-based treatment for solid tumors does not increase overall survival but may increase toxicity. Methods Population, Intervention, Control, Outcome, Study Design; Preferred Reporting Items for Systematic Reviews and Meta-Analyses; and Meta-analysis of Observational Studies in Epidemiology methods were used to identify prospective randomized studies including patients with solid tumor cancers treated with radiotherapy with or without RTKis. Extracted variables included use of radiotherapy vs chemoradiotherapy, RTKi type (antibody vs small molecule), outcomes, and toxicities. The primary endpoint was overall survival; the secondary endpoint was grade 3+ toxicity. Random-effects meta-analyses were performed for each outcome measure. All statistical tests were 2-sided. Results A total of 405 studies met the initial search criteria, of which 13 prospective randomized trials of radiotherapy with or without RTKi met the inclusion criteria, encompassing 5678 patients. The trials included cancers of the head and neck (6 trials, 3295 patients), esophagus (3 trials, 762 patients), lung (2 trials, 550 patients), and brain (2 trials, 1542 patients). Three studies evaluated a small molecule and radiotherapy in 949 patients, and 10 studies evaluated antibodies and radiotherapy in 4729 patients. The addition of RTKis to radiotherapy-based treatment did not improve overall survival (hazard ratio = 1.02, 95% confidence interval = 0.90 to 1.15, P = .76) but increased grade 3+ toxicity (relative risk = 1.18, 95% confidence interval = 1.06 to 1.33, P = .009). Conclusions The addition of RTKis to radiotherapy does not improve survival and worsens toxicity.