Hematologic Toxicities With Targeted Drugs in Malignant Solid Tumors: A Systematic Review and Network Meta-Analysis
Bo Wen, Xinpu Han, Tianxiang Li, Jing WangObjective
This systematic review and network meta-analysis aimed to evaluate the incidence and safety ranking of hematological toxicities associated with targeted therapies for malignant solid tumors in RCTs.
Methods
PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to June 2026 for RCTs in adults with malignant solid tumors receiving at least one targeted agent and reporting anemia. Anemia was the main result, while other secondary outcomes included thrombocytopenia, neutropenia, leukopenia, etc. Subgroup analyses were carried out according to research phase, tumor type, country category, etc. ROB was assessed using the Cochrane tool. Consistency was evaluated by node-splitting and loop-specific approaches. Sensitivity analyses were performed by sequentially removing individual trials. Publication bias was assessed using funnel plots. Treatment safety was ranked using the SUCRA.
Results
27 phase II/III RCTs (n = 8985) were included. The incidence of grades 1-5 anemia was 25.79%, and grades 3-5 anemia was 6.53%. Among single targeted agents, erlotinib had the highest all-grade anemia incidence, while alectinib had the lowest severe-grade anemia incidence. Targeted therapy combined with chemotherapy generally showed higher hematological toxicity than single-agent or doublet targeted therapy. Tepotinib plus gefitinib ranked highest in safety for both all-grade and severe-grade anemia, whereas afatinib plus chemotherapy ranked lowest for severe-grade anemia. For secondary outcomes, erlotinib monotherapy carried the highest risk of all-grade and severe-grade neutropenia, FN, and WBC count decrease among single agents. Overall, 136 treatment-related deaths were recorded, of which only 2 were attributed to hematological toxicity. Subgroup analysis revealed that, apart from the type of tumor, it was the key factor contributing to the heterogeneity. Sensitivity analyses confirmed the robustness of the primary findings.
Conclusions
Each targeted therapeutic regimen has a unique safety profile. In clinical practice, early detection and treatment of hematological toxicities linked to targeted medications are crucial.