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

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 bod...

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Autores principales: Hopkins, Ashley M., Nguyen, Anh-Minh, Karapetis, Christos S., Rowland, Andrew, Sorich, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210178/
https://www.ncbi.nlm.nih.gov/pubmed/30326638
http://dx.doi.org/10.3390/cancers10100384
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author Hopkins, Ashley M.
Nguyen, Anh-Minh
Karapetis, Christos S.
Rowland, Andrew
Sorich, Michael J.
author_facet Hopkins, Ashley M.
Nguyen, Anh-Minh
Karapetis, Christos S.
Rowland, Andrew
Sorich, Michael J.
author_sort Hopkins, Ashley M.
collection PubMed
description 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.
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spelling pubmed-62101782018-11-02 Risk Factors for Severe Diarrhea with an Afatinib Treatment of Non-Small Cell Lung Cancer: A Pooled Analysis of Clinical Trials Hopkins, Ashley M. Nguyen, Anh-Minh Karapetis, Christos S. Rowland, Andrew Sorich, Michael J. Cancers (Basel) Article 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. MDPI 2018-10-15 /pmc/articles/PMC6210178/ /pubmed/30326638 http://dx.doi.org/10.3390/cancers10100384 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hopkins, Ashley M.
Nguyen, Anh-Minh
Karapetis, Christos S.
Rowland, Andrew
Sorich, Michael J.
Risk Factors for Severe Diarrhea with an Afatinib Treatment of Non-Small Cell Lung Cancer: A Pooled Analysis of Clinical Trials
title Risk Factors for Severe Diarrhea with an Afatinib Treatment of Non-Small Cell Lung Cancer: A Pooled Analysis of Clinical Trials
title_full Risk Factors for Severe Diarrhea with an Afatinib Treatment of Non-Small Cell Lung Cancer: A Pooled Analysis of Clinical Trials
title_fullStr Risk Factors for Severe Diarrhea with an Afatinib Treatment of Non-Small Cell Lung Cancer: A Pooled Analysis of Clinical Trials
title_full_unstemmed Risk Factors for Severe Diarrhea with an Afatinib Treatment of Non-Small Cell Lung Cancer: A Pooled Analysis of Clinical Trials
title_short Risk Factors for Severe Diarrhea with an Afatinib Treatment of Non-Small Cell Lung Cancer: A Pooled Analysis of Clinical Trials
title_sort risk factors for severe diarrhea with an afatinib treatment of non-small cell lung cancer: a pooled analysis of clinical trials
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6210178/
https://www.ncbi.nlm.nih.gov/pubmed/30326638
http://dx.doi.org/10.3390/cancers10100384
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