Dermatologic adverse events associated with afatinib: an oral ErbB family blocker

Lacouture, Mario E.; Schadendorf, Dirk; Chu, Chia-Yu; Uttenreuther-Fischer, Martina; Stammberger, Uz; O'Brien, Dennis E.; Hauschild, Axel

doi:10.1586/era.13.30

Cited by 84 publications

(56 citation statements)

References 30 publications

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“…43 In terms of patient education, patients should be advised to care for their oral health by using a brush with soft bristles, sodium bicarbonate and alcohol-free mouthwash; taking special care of dentures as they can cause oral sores. 47,48 Food should be consumed cold or at room temperature, and food that is acidic, spicy, salty or coarse should be avoided. Patients should drink a lot of water, preferably using a straw to sip liquids.…”

Section: Management Of Stomatitis/mucositismentioning

confidence: 99%

Management of epidermal growth factor receptor tyrosine kinase inhibitor‐related cutaneous and gastrointestinal toxicities

Tan

Chin

et al. 2017

Asia-Pac J Clncl Oncology

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Patients with advanced stage non-small cell lung cancer with sensitizing epidermal growth factor receptor (EGFR) mutations using EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib and afatinib as first-line treatment had better progression-free survival, overall response rate and quality of life than those on chemotherapy. Although EGFR TKIs are commonly associated with skin-related (rash, xerosis and paronychia) and gastrointestinal-related (diarrhea and stomatitis) adverse events (AEs), these effects are usually mild. But severe cases can occur, significantly affecting patient's well-being, treatment compliance and quality of life. Therefore, patient education, early diagnosis, and prophylactic treatment are important strategies to optimally manage EGFR TKI-related adverse effects. In this review, we summarize the commonly encountered EGFR TKI-related AEs and provide a current overview of AE management in local practice with a focus on Asian patients. K E Y W O R D Sadverse drug events, gastrointestinal tract, mutations, non-small cell lung cancer, skin BACKGROUNDEighty percent of lung cancers are advanced-stage non-small cell lung cancer (NSCLC). (1) Epidermal growth factor receptor (EGFR) gene mutation, which is a major and potent oncogenic driver in NSCLC is a therapeutic target, with EGFR tyrosine kinase inhibitors (EGFR TKIs), altering the pattern of care in patients with advanced stage NSCLC.With EGFR TKIs (erlotinib, gefitinib and afatinib) as first-line treatment for patients with advanced stage NSCLC with sensitizing EGFR mutations, higher progression-free survival, overall response rate and quality of life than chemotherapy can be achieved. 1 These drugs are generally well tolerated as they have a predictable toxicity profile and less serious toxicities than traditional cytotoxic chemotherapy. 2 Nevertheless, EGFR TKIs can still produce severe adverse events (AEs) and impair quality of life.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. wileyonlinelibrary.com/journal/ajco 23

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Section: Management Of Stomatitis/mucositismentioning

confidence: 99%

Management of epidermal growth factor receptor tyrosine kinase inhibitor‐related cutaneous and gastrointestinal toxicities

Tan

Chin

et al. 2017

Asia-Pac J Clncl Oncology

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“…Recent results from LUX-Lung 6, the companion Phase III study to LUX-Lung 3, reinforce the superiority of afatinib over chemotherapy (gemcitabine/cisplatin) alone in the EGFR mutation-positive NSCLC patient population [75]. The safety profile of afatinib has demonstrated consistency across studies; the most frequent adverse events, diarrhoea and rash, were manageable [76,77]. On the basis of these key studies, afatinib monotherapy has gained approval for the treatment of EGFR TKI-naïve patients with locally advanced or metastatic NSCLC and activating EGFR mutations.…”

Section: Pelitinib Av-412/mp-412 and Bms-599626mentioning

confidence: 94%

Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

Rolfo

Giovannetti

Hong

et al. 2014

Cancer Treatment Reviews

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a b s t r a c tIntroduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal-epithelial transition factor (MET) amplification, epithelial-mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeutic strategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking of multiple members of the ErbB family. Several molecules which target multiple ErbB receptors are being investigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitinib and lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance (T790M) mutations, are currently under clinical development. Other therapeutic strategies include inhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 or http://dx.doi.org/10.1016/j.ctrv.2014.05.009 0305-7372/Ó 2014 Elsevier Ltd. All rights reserved.Abbreviations: AEG-1, astrocyte elevated gene-1; ALK, anaplastic lymphoma kinase; ATP, adenosine triphosphate; BARD1, BRCA1-associated protein 1; BIM, B-cell lymphoma 2 interacting mediator of cell death; BRAF, v-raf murine sarcoma viral oncogene homolog B1; BRCA1, breast cancer 1, early onset; CNS, central nervous system; CRKL, crk-like protein; DCR, disease control rate; EGFR, epidermal growth factor receptor; EMT, epithelial-mesenchymal transformation; EphB4, ephrin type-B receptor 4; ER, oestrogen receptor; ERK, extracellular-signal-regulated kinases; HER, human epidermal growth factor receptor; HGF, hepatocyte growth factor; HSP90, heat shock protein 90; IGF-1R, insulin-like growth factor 1 receptor; KRAS, Kirsten rat sarcoma viral oncogene homologue; MBP-QP, mutation-biased PCR quenching probe; MEK, mitogen-activated protein kinase; MET, mesenchymal-epithelial transition factor; mRNA, messenger RNA; mTOR, mammalian target of rapamycin; NF-jB, nuclear factor kappa-light-chainenhancer of activated B cells; NSCLC, non-small-cell lung cancer; ORR, overall response rate; OS, overall survival; PARP, poly (ADP-ribose) polymerase; PCR, polymerase chain reaction; PFS, progression free survival; PI3K, phosphoinositide-3-kinase; PIK3CA, phosphoinositide-3-kinase, catalytic, alpha polypeptide; PTEN, phosphatase and tensin homologue; RECIST, Response Evaluation Criteria in Solid Tumours; RR, response rate; SCLC, small-cell lung cancer; TGF, transforming growth factor; TKI, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor. E-mail address: christian.rolfo@uza.be (C. Rolfo).Can...

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“…1 Survival of patients with advanced NSCLC is poor, with <10% survival at 5 y with standard chemotherapy and a median overall survival of <14 months. 2,3 Treatment with reversible tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR; ErbB1) has resulted in responses in only a subset of NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

“…10 This article reports the case of a female smoker presenting with Stage IV, poorly differentiated, large cell carcinoma of the lung, an uncommon NSCLC histological subtype. 1,8 Despite being a smoker and not having adenocarcinoma histology, the patient responded to the reversible EGFR TKI erlotinib for more than 3 y and, following progression, attained an additional year of survival with afatinib.…”

Section: Introductionmentioning

confidence: 99%

Prolonged survival with erlotinib followed by afatinib in a caucasian smoker with metastatic, poorly differentiated large cell carcinoma of the lung: a case report

Má

2015

Cancer Biology & Therapy

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Keywords: afatinib, case report, EGFR mutation, non-small cell lung cancerAbbreviations: CT, computed tomography; EGFR, ErbB1, epidermal growth factor receptor; NSCLC, non-small cell lung cancer; PFS, progression-free survival; PR, partial response; RUL, right upper lobe; TKI, tyrosine kinase inhibitor.Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR; ErbB1) -either exon 19 deletions or exon 21 point mutations -are associated with hypersensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR mutations are more frequently found in females, non-smokers, Asians, and patients with adenocarcinoma. We report the case of a 51-year-old Caucasian woman with metastatic NSCLC harboring an EGFR exon 19 deletion although she was a smoker and had a poorly differentiated large cell carcinoma. Following a partial response on 4 months of chemotherapy, the patient progressed and was treated with the reversible EGFR TKI erlotinib for 3 y. The patient then developed resistance to erlotinib and went on to receive the irreversible ErbB Family Blocker afatinib for 1 year, attaining a partial response at 4 months. The impressive survival time attained by our patient highlights the clinical benefit of targeting one or more members of the ErbB Family in patients with disseminated NSCLC and EGFR activating mutations.

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Dermatologic adverse events associated with afatinib: an oral ErbB family blocker

Cited by 84 publications

References 30 publications

Management of epidermal growth factor receptor tyrosine kinase inhibitor‐related cutaneous and gastrointestinal toxicities

Management of epidermal growth factor receptor tyrosine kinase inhibitor‐related cutaneous and gastrointestinal toxicities

Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

Prolonged survival with erlotinib followed by afatinib in a caucasian smoker with metastatic, poorly differentiated large cell carcinoma of the lung: a case report

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