Precision therapy in patients with non–small cell lung cancer refers to the oral TKIs that are used to target genetic alterations. These targetable alterations include mutations in the EGFR gene, the BRAF V600E point mutation, and MET exon 14 skipping mutations, as well as rearrangements of the ALK, ROS1, and RET genes. Testing for these oncogenic alterations not only identifies the most effective therapy for the individual patient but also has the potential to reduce treatment-related adverse events by avoiding therapies that are less likely to be effective. 

TKIs tend to have predictable patterns of adverse events, and one needs to be proactive about them. The adverse events associated with TKIs most commonly consist of skin reactions, gastrointestinal events, and generalized fatigue. It is important to have conversations with patients regarding the possibility of adverse events so that they are aware and prepared. Importantly, they must be taught about skin care and gastrointestinal management up front. 

EGFR inhibitors are commonly associated with rash and diarrhea. ALK inhibitors are also associated with numerous gastrointestinal effects, such as nausea/vomiting, diarrhea, and constipation, as well as fatigue and changes in vision. In addition, ALK inhibitors can produce pulmonary toxicity, so patients, particularly those with pulmonary dysfunction, should be closely monitored. The most common side effects associated with agents that target BRAF mutations include rash and cutaneous toxicities, such as hyperkeratosis, headache, arthralgia, and pyrexia. 

Proactive discussions and proper management of these adverse events are key to avoiding treatment interruptions and discontinuation, as well as to optimizing treatment adherence. The goal is to get patients through the full course of treatment. Rash can be treated with topical and systemic corticosteroids and dosage adjustments/interruptions, but the reactions are complicated by the long half-lives of these agents. Topical clindamycin is also useful for TKI-associated rash. Fatigue is typically seen early in treatment with TKIs and tends to diminish over time, so we recommend rest and exercise until it improves with time.