Expert Consensus on the Management of Adverse Events from EGFR Tyrosine Kinase Inhibitors in the UK

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as gefitinib, erlotinib, and afatinib are standard-of-care for first-line treatment of EGFR-mutant advanced non-small cell lung cancer (NSCLC). These drugs have a proven benefit in terms of higher response rate, delaying progression and improvement of quality of life over palliative platinum-based chemotherapy. The most common adverse events (AEs) are gastrointestinal (GI) (diarrhoea and stomatitis/mucositis) and cutaneous (rash, dry skin and paronychia). These are usually mild, but if they become moderate or severe, they can have a negative impact on the patient’s quality of life (QOL) and lead to dose modifications or drug discontinuation. Appropriate management of AEs, including prophylactic measures, supportive medications, treatment delays and dose reductions, is essential. A consensus meeting of a UK-based multidisciplinary panel composed of medical and clinical oncologists with a special interest in lung cancer, dermatologists, gastroenterologists, lung cancer nurse specialists and oncology pharmacists was held to develop guidelines on prevention and management of cutaneous (rash, dry skin and paronychia) and GI (diarrhoea, stomatitis and mucositis) AEs associated with the administration of EGFR-TKIs. These guidelines detail supportive measures, treatment delays and dose reductions for EGFR-TKIs. Although the focus of the guidelines is to support healthcare professionals in UK clinical practice, it is anticipated that the management strategies proposed will also be applicable in non-UK settings.

Skin problems and EGFR-tyrosine kinase inhibitor

“…Some guidelines to manage the EGFR inhibitor-associated skin rash are available (51)(52)(53)(54)(55)(56)(57)(58). However, most of the statements are made from the expert opinion or consensus, case report, single-arm prospective trial or retrospective analysis, and only a few randomized trial data are incorporated in these guidelines.…”

Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials

“…Key treatmentrelated AEs include diarrhea, rash/acne, stomatitis and nail effects, some of which (e.g. diarrhea) appear to be more pronounced with afatinib [15]. However, these AEs are predictable and manageable with supportive care and treatment interruptions and/or dose modifications [15].…”

“…diarrhea) appear to be more pronounced with afatinib [15]. However, these AEs are predictable and manageable with supportive care and treatment interruptions and/or dose modifications [15]. When choosing first-line treatment, it is important to consider the risk-benefit profile of individual agents, including the impact of management strategies and options to address interpatient variability.…”

Novel Therapies Against Aggressive Differentiated Thyroid Carcinomas

“…The assessment of AEs should comprehend severity scales like the common terminology criteria for AEs since this may help to assist in treatment reductions/withdrawals [39]. Table 2 describes the most common AEs and strategies to manage them [11,[40][41][42][43][44][45].…”