When starting patients with NSCLC on targeted therapies, it is important to have a teaching session with them to make sure that they understand how they are supposed to be taking their medication. This is critically important because patients must know when to take these targeted therapies, including in relation to meals. We ask a nurse or pharmacist to call and check in with the patient approximately 7 to 14 days after initiating therapy. It is also important to monitor for adverse events. Since the tyrosine kinase inhibitors (TKIs) we use generally have a half-life of approximately 24 to 48 hours, there will be a gradual increase in side effects until steady state is reached in approximately 6 days. Osimertinib is currently the agent of choice as initial therapy in patients with EGFR mutations. Its role as the preferred agent is based on a longer progression-free survival vs the older TKIs, gefitinib and erlotinib, but it has a somewhat different side-effect profile compared with these older agents. While diarrhea, nausea, and vomiting can be seen with osimertinib, the risk is substantially less than with either gefitinib or erlotinib. Rash and nail effects characterized by slowed growth and inflammation at the base of nail beds are common with the use of all of these agents, but, overall, osimertinib is better tolerated compared with the older TKIs. An adverse event that is a bit more common with osimertinib use than what is seen with gefitinib and erlotinib use is cardiomyopathy and decreased ejection fraction. Osimertinib is also associated with the development of interstitial lung disease, so you need to monitor for this. 

Alectinib is the agent of choice for patients with ALK-rearranged tumors based on a much longer progression-free survival (3 years vs 11-12 months) and a better safety profile compared with crizotinib. Crizotinib causes visual disorders (including blurred vision, visual impairment, vitreous floaters, reduced visual acuity, and diplopia) in approximately 20% of patients, but in only 5% of those receiving alectinib. Crizotinib also causes nausea, vomiting, and diarrhea, whereas these effects are nearly absent in those taking alectinib. Further, both alectinib and crizotinib can cause transaminase elevations.

The combination of dabrafenib and trametinib for the treatment of BRAF V600E–mutant NSCLC is associated with a unique set of side effects and is somewhat challenging to administer. Patients may develop fevers up to 103 °F to 104 °F, and, when that happens, you must discontinue the drug. If the fever does not resolve within 24 hours, a burst of prednisone may help because patients are usually quite symptomatic. The other issue with the combination is grade 3/4 nausea and vomiting, which has been reported in a small but significant percentage of patients. This regimen can also cause skin cancers, so patients need to be monitored for this. Finally, trametinib, an MEK kinase inhibitor, can cause visual disturbances and cardiac dysfunction; individuals on this drug should be monitored with eye examinations and routine echocardiograms.