Complications following small-molecule inhibitors for non-small cell lung cancer

Targeted therapies for oncogene-driven non-small cell lung cancer (NSCLC) have transformed precision oncology by enabling treatment tailored to specific molecular alterations and substantially improving outcomes in advanced disease. However, these agents are associated with distinct patterns of treatment-related toxicities affecting multiple organ systems and may impact long-term treatment success.

This review summarizes the spectrum of toxicities associated with the treatment of EGFR, ALK, BRAF, ROS1, MET, RET, KRAS, HER2, and NTRK. Evidence from pivotal clinical trials and real-world studies is discussed to describe toxicity incidence, underlying mechanisms, and current management strategies. Emphasis is placed on hepatic, gastrointestinal, dermatologic, neurologic, cardiovascular, and pulmonary adverse events, as well as on structured monitoring and multidisciplinary toxicity management approaches. A structured literature search was conducted in PubMed/MEDLINE, Embase, and Web of Science, including peer-reviewed publications.

Early recognition and proactive management of toxicity are essential to maintain treatment adherence, optimize safety, and preserve quality of life. Emerging biomarkers of toxicity and resistance are expected to refine individualized management and guide the development of next-generation inhibitors with improved tolerability. Integrating precision toxicity management into routine clinical practice will be critical to maximizing the therapeutic benefit of targeted therapies in oncogene-driven NSCLC.