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Cancers 2018, 10(10), 384;

Risk Factors for Severe Diarrhea with an Afatinib Treatment of Non-Small Cell Lung Cancer: A Pooled Analysis of Clinical Trials

College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia
Department of Medical Oncology, Flinders Medical Centre, Adelaide 5042, Australia
Author to whom correspondence should be addressed.
Received: 13 September 2018 / Revised: 3 October 2018 / Accepted: 10 October 2018 / Published: 15 October 2018
(This article belongs to the Special Issue Epidermal Growth Factor Receptor Signaling in Cancer)
PDF [505 KB, uploaded 15 October 2018]


Afatinib is an effective therapy for metastatic non-small cell lung cancer (NSCLC) but it is associated with a relatively high incidence of severe diarrhea. The association between pre-treatment candidate predictors (age, sex, race, performance status, renal function, hemoglobin, and measures of body mass) and severe (grade ≥ 3) diarrhea was evaluated using logistic regression with pooled individual participant data from seven clinical studies. A risk score was developed based on the count of major risk factors. Overall, 184 of 1151 participants (16%) experienced severe diarrhea with use of afatinib. Body weight, body mass index, and body surface area all exhibited a prominent non-linear association where risk increased markedly at the lower range (p < 0.005). Low weight (<45 kg), female sex, and older age (≥60 years) were identified as major independent risk factors (p < 0.01). Each risk factor was associated with a two-fold increase in the odds of severe diarrhea, and this was consistent between individuals commenced on 40 mg or 50 mg afatinib. A simple risk score based on the count of these risk factors identifies individuals at lowest and highest risk (C-statistic of 0.65). Risk of severe diarrhea for individuals commenced on 40 mg afatinib ranged from 6% for individuals with no risk factors to 33% for individuals with all three risk factors. View Full-Text
Keywords: EGFR inhibitor; diarrhea; toxicity; prediction model; adverse event EGFR inhibitor; diarrhea; toxicity; prediction model; adverse event

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Hopkins, A.M.; Nguyen, A.-M.; Karapetis, C.S.; Rowland, A.; Sorich, M.J. Risk Factors for Severe Diarrhea with an Afatinib Treatment of Non-Small Cell Lung Cancer: A Pooled Analysis of Clinical Trials. Cancers 2018, 10, 384.

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