Identifying EGFR Mutations in NSCLC and Optimizing Therapy - Episode 4

Patient-reported Outcomes with TKIs

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Beyond measuring survival benefits in clinical trials it is important to examine more humanistic measures, such as quality of life (QoL), which is often related to the extent a patient experiences side effects. Using patient reported outcomes can not only corroborate physician reports of toxicity, but can assess patients’ experiences. Lecia V. Sequist, MD, MPH, stresses that QoL is one of the most important aspects of treatment for many patients.

The LUX-Lung-3 and LUX-Lung-6 trials administered extensive patient questionnaires. These data showed that patients in the afatinib arm, compared with the chemotherapy arm, had a more rapid and deeper improvement in many of their cancer-related symptoms, including cough, shortness of breath, and chest pain. In addition, the data showed an overall global improvement in QoL that was more dramatic with afatinib compared with chemotherapy. These patient-reported outcomes help demonstrate that targeted therapy, such as tyrosine-kinase inhibitors (TKIs), can improve patients’ QoL.

Drug-related side effects are often more mild with targeted agents compared with other treatment options. Still, patients must be prepared to experience some side effects, and physicians must be prepared to manage these adverse events. The two critical parts of the body that harbor EGFR are the skin and the gut, explains Corey J. Langer, MD. As a result, the two most common side effects related to EGFR inhibition are maculopapular rash and diarrhea.

For patients experiencing rash, basic interventions can include topical emollients; however, topical antibiotics may be necessary for a pustule rash, or if the rash spreads to the face. Some physicians may choose to use prophylactic antibiotics, such as doxycycline, which can mitigate the severity of rash after a patient has started the therapy.

Approximately 60% to 80% of patients taking TKIs will experience diarrhea, and 10% to 15% of these patients will have grade 3 diarrhea. Patients should be instructed to take antidiarrheal agents (eg, Imodium) at the first sign of symptoms. These antidiarrheal agents can be titrated based on the severity.

The more common side effects usually occur a couple of weeks after starting a TKI, and often will start to dissipate over time, without any dose adjustment. Other occasional side effects include stomatitis, which may be more common with afatinib, and paronychia and digital fissure, which can be easily treated. A more severe, but rare, side effect is interstitial lung disease (ILD) and interstitial pneumonia, which is heralded by shortness of breath, cough, and hypoxia. When ILD is diagnosed, the TKI should be discontinued immediately.