Prevention and treatment of mucocutaneous adverse reactions associated with epidermal growth factor receptor inhibitors / 中华预防医学杂志

The epidermal growth factor receptor (EGFR) signaling is aberrantly overexpressed in many solid malignancies, making it an important target for anti-cancer biologic agents. Among them, epidermal growth factor receptor inhibitors (EGFRIs), which have been widely used in clinical practice, include anti-EGFR monoclonal antibodies and tyrosine kinase inhibitors. A proportion of patients treated with EGFRIs develop specific, dose-dependent skin toxicity such as papulopustular rash, paronychia, xerosis and itch. These side effects can cause physical and psychosocial discomfort that may result in dose reduction, discontinuance, or replacement of the current EGFRIs treatment. Correct diagnosis and treatment of these skin and mucosal adverse effects associated with EGFRIs is of great significance for the tertiary prevention of malignant tumors. A review on EGFRI-related mucocutaneous adverse reactions is presented here, focusing on the pathogenesis, the various clinical manifestations, the strategies for prevention and treatment of these conditions.

Tratamientos de primera línea para pacientes estadio IV con adenocarcinoma pulmonar de mutación EGFR / First-line treatments for stage IV patients with EGFR-mutated lung adenocarcinoma

Lung cancer is one of the leading causes of death in the world. Current treatments act directly on the signal transduction pathways in cancer cells, mainly. One of the main pathways is associated with the Epidermal Growth Factor (EGFR), whose mutations leads to uncontrolled cell proliferation and a higher rate of cell invasion. Activating mutations in the EGFR gene, which includes deletions in exon 19 and the L858R mutation in exon 21, were detected in most patients with non-small cell lung cancer (NSCLC). Studies of EGFR tyrosine kinase inhibitors (EGFR-TKIs) such as Gefitinib, Erlotinib and Afatinib, compared with platinum-based treatments, showed that EGFR-TKIs produce increased disease-free survival, although only in patients whose cancers harbor activating mutations in the EGFR gene. Clinical trials also demonstrated that EGFR-TKIs are effective as first-line therapies in stage IV pulmonary adenocarcinoma. Here, the main aspects of the activation of the EGFR pathway in NSCLC will be reviewed, highlighting the importance for health professionals of correctly identifying activating mutations in the EGFR gene and acting quickly at the molecular level based on aforementioned treatments. (AU)

Potential life years not saved due to lack of access to anti-EGFR tyrosine kinase inhibitors for lung cancer treatment in the Brazilian public healthcare system: Budget impact and strategies to improve access. A pharmacoeconomic study

ABSTRACT BACKGROUND: Lung cancer is the fourth most common cancer in Brazil. In the 2000s, better understanding of molecular pathways led to development of epidermal growth factor receptor (EGFR)-targeted treatments that have improved outcomes. However, these treatments are unavailable in most Brazilian public healthcare services (Sistema Único de Saúde, SUS). OBJECTIVE: To assess the potential number of years of life not saved, the budget impact of the treatment and strategies to improve access. DESIGN AND SETTING: Pharmacoeconomic study assessing the potential societal and economic impact of adopting EGFR-targeted therapy within SUS. METHODS: We estimated the number of cases eligible for treatment, using epidemiological data from the National Cancer Institute. We used data from a single meta-analysis and from the Lung Cancer Mutation Consortium (LCMC) study as the basis for assessing differences in patients' survival between use of targeted therapy and use of chemotherapy. The costs of targeted treatment were based on the national reference and were compared with the amount reimbursed for chemotherapy through SUS. RESULTS: There was no life-year gain with EGFR-targeted therapy in the single meta-analysis (hazard ratio, HR, 1.01). The LCMC showed that 1,556 potential life-years were not saved annually. We estimated that the annual budget impact was 125 million Brazilian reais (BRL) with erlotinib, 48 million BRL with gefitinib and 52 million BRL with afatinib. Their incremental costs over chemotherapy per life-year saved were 80,329 BRL, 31,011 BRL and 33,225 BRL, respectively. A drug acquisition discount may decrease the budget impact by 30% (with a 20% discount). A fixed cost of 1,000 BRL may decrease the budget impact by 95%. CONCLUSION: Reducing drug acquisition costs may improve access to EGFR-targeted therapy for lung cancer.

Clinical experience on use of oral EGFR-TKIs as first-line treatment of advanced NSCLC from a tertiary care centre in North India and implications of skin rash.

Background. Limited data are available from India on treatment outcomes with oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in newly diagnosed non-small cell lung cancer (NSCLC). We studied the demographic profile and treatment outcomes of patients with NSCLC, receiving first-line treatment with oral EGFR-TKIs. Methods. Retrospective study of newly diagnosed NSCLC patients treated with oral EGFR-TKIs over a 4-year period at a tertiary care institute in North India. Results. Of 76 patients studied, females and non-smokers constituted 32.9% and 48.7%, respectively. Majority of patients had adenocarcinoma (59.2%), stage IV (64.5%) disease and Karnofsky performance status <70 (74.5%). Gefitinib was the most frequently used EGFR-TKI (92.1%). Most common indication for the use of EGFR-TKIs was poor performance status (65.8%). Among assessable patients, disease control and progressive disease were evident in 66% and 34%, respectively. Most common side effects were skin rash (17%) and diarrhoea (10.6%). Patients with and without skin rash differed significantly in relation to objective response to treatment (100% versus 23.1%) and overall survival (median not reached versus 178 days). On multivariate logistic regression analysis, malignant pleural effusion was associated with occurrence of rash (odds ratio=0.19; 95% confidence interval = 0.04-0.95; p=0.04). Conclusions. Oral EGFR-TKIs appear to be useful for the treatment of clinically selected patients with advanced NSCLC. Occurrence of skin rash was independently associated with treatment response and better survival in the current study.

Novel targeted agents for the treatment of bladder cancer: translating laboratory advances into clinical application: [review]

Bladder cancer is a common and frequently lethal cancer. Natural history studies indicate two distinct clinical and molecular entities corresponding to invasive and non-muscle invasive disease. The high frequency of recurrence of noninvasive bladder cancer and poor survival rate of invasive bladder cancer emphasizes the need for novel therapeutic approaches. These mechanisms of tumor development and promotion in bladder cancer are strongly associated with several growth factor pathways including the fibroblast, epidermal, and the vascular endothelial growth factor pathways. In this review, efforts to translate the growing body of basic science research of novel treatments into clinical applications will be explored.