Use Of Epidermal Growth Factor Receptor Inhibitors Research Articles

Economic analysis of biomarker-based anti-EGFR therapies in metastatic colorectal cancer in the Austrian context

In metastatic colorectal cancer (mCRC), multimodal therapeutic strategies and diagnostics have continuously improved patient survival. The aim of our investigation was to relate this enhanced clinical outcome to treatment costs based on predictive biomarker scenarios guiding epidermal growth factor receptor (EGFR) targeting in a developed country. We performed a cost-effectiveness analysis for the combination of EGFR inhibitors with chemotherapy in the first-line treatment of mCRC. Resource use estimates were based on actual data from two oncological departments and on clinical outcomes adapted from published trials. Comparative analyses for the use of EGFR inhibitors were based on three biomarker scenarios (sensitivity: 35%, 55% and 75%) to estimate their incremental cost-effectiveness and were completed by sensitivity analyses. Using FOLFIRI+cetuximab, preselection for EGFR therapy with KRAS testing prolonged progression-free survival with average savings of 913 €/month/patient (scenario 1) and average savings of 1811 €/month/patient when testing the whole RAS-family (scenario 2). In a future but realistic scenario, up 39% of treatment costs could be saved with almost three life–years gained (LYG). The incremental cost/LYG was 212,083 € (116,646–1,866,332 €) for unselected EGFR therapy, 32,251 € (30,294–43,488 €) for EGFR following KRAS testing, 19,172 € (15,369–28,611 €) for the all RAS scenario, and 12,369 € (3865–18,533 €) for a future biomarker scenario. In the therapy of mCRC, predictive biomarker testing has shown to be effective and cost saving. For further improvement, a strong research focus on predictive biomarkers is considered highly efficient to promote precision oncology by alleviating the pressure on the healthcare system.

489P - Verification of guideline conform mCRC treatment with EGFR inhibitors with real-world evidence data from EU5 countries

Background: The EGFR inhibitors cetuximab and panitumumab are indicated for patients suffering from metastatic colorectal cancer (mCRC), which are RAS wildtype. The aim of this analysis is to verify with real-world data whether the drug usage of those EGFR inhibitors reflects clinical guidelines with regards to their genomic profile. Methods: Anonymized patients-level data collected through a large web-based survey between April 2017 and March 2018 was used. The study reported patient case history information across all cancer types in 5EU (France, Germany, Italy, Spain & UK). Treatment information and biomarker testing information on 5248 mCRC drug treated patients were analyzed. Results: Evaluating KRAS and NRAS biomarkers status, real-world data analysis showed that 18,9% of mCRC patients were not tested for N-RAS mutation and 11,4% were not tested for K-RAS mutation. 16% of the mCRC population were RAS mutant. However, 3,2% of these patients received cetuximab and panitumumab even though they did not qualify for this treatment, due to their RAS mutation. Among all mCRC patients who were RAS wildtype, 49,4% of them received cetuximab or panitumumab. Conclusions: This analysis of real-word data showed that biomarkers testing is not carried out in all mCRC patients. Secondly, the use of EGFR inhibitors in the RAS mutant mCRC patient population demonstrates a misalignment with clinical guidelines. Howver, most of patients receiving EGFR inhibitors are RAS wildtype, which implies that the majority of mCRC patients receiving EGFR inhibitors is treated according to medical guidelines regarding their genomic profile. Legal entity responsible for the study: IQVIA Commercial GmbH & Co. OHG. Funding: Has not received any funding. Disclosure: L. Hoyer, N. Schmidt: Employee of IQVIA Commercial GmbH & Co. OHG.

EGFR inhibitors in the treatment of colorectal cancer

This ar cle discusses the use of EGFR inhibitors in the treatment of pa ents with colorectal cancer. The mechanisms of their ac on, speci fi c manifesta ons of toxicity are considered. A review of current literature data on the use of both approved for clinical use (cetuximab, panitumumab) and an -EGFR an bodies at the stage of clinical trials is presented. EGFR inhibitors are one of the main groups of targeted drugs used to treat pa ents with colorectal cancer. The correla on between toxicity and e ffi cacy of these drugs is discussed separately. The scope of their applica on is limited to the treatment of disseminated forms of the disease, but in the future the number of available an -EGFR an bodies may grow, the possibility of their use in new condi ons, including in the framework of chemoradiotherapy.

EGFR Inhibitors and Cutaneous Complications: A Practical Approach to Management

Epidermal growth factor receptor inhibitors (EGFRIs) are increasingly being used for malignancies of epithelial origin. Though these therapies are better tolerated than conventional chemotherapy, they have unique side-effect profiles that are related to their mechanism of action. Given the function of the epidermal growth factor receptor in the skin, nails, and hair, dermatologic side effects are commonly seen with the use of EGFRIs. This review includes a practical approach to recognizing and treating the most common dermatologic side effects seen with EGFRIs, including papulopustular eruptions, nail changes, xerosis and pruritus, hair changes, mucositis, and radiation dermatitis exacerbations.

Dermopathy associated with cetuximab and panitumumab: investigation of the usefulness of moisturizers in its management.

AimsLimited data regarding the objective evaluation of skin exsiccation caused by epidermal growth factor receptor (EGFR) inhibitors exist. Objective indices were applied to evaluate the usefulness of a moisturizer against skin exsiccation associated with the use of EGFR inhibitors in cancer patients.Patients and methodsPatients with either colorectal or head and neck cancer treated with either cetuximab or panitumumab were randomly assigned 1:2 to the prophylactic-treatment arm, where participants received prophylactical moisturizer treatment (heparinoid preparation, Hirudoid®), or to the symptomatic-treatment arm, where moisturizer was applied after the onset of cutaneous symptoms. Patients were observed for 6 weeks after the start of the administration of EGFR inhibitor.ResultsA total of 15 patients were included and assessed: 6 in the prophylactic treatment group and 9 in the symptomatic treatment group. We evaluated the effect of EGFR inhibitors on the physiologic function of the skin. Administration of EGFR inhibitors resulted in a continued reduction in the moisture content of the horny layer and a decrease in cutaneous sebum levels. Skin observation revealed frequent development of an acneiform rash and significantly higher exsiccation and exfoliation scores. Administration of EGFR inhibitor was associated with a decrease in the horny layer moisture content and lower cutaneous sebum levels in the symptomatic treatment group. In contrast, levels of both the indicators were increased in the prophylactic treatment group. Moreover, the EGFR inhibitor-associated increase in exsiccation and exfoliation scores were minimized in the prophylactic treatment group relative to the symptomatic treatment group.ConclusionApplication of a moisturizer is effective against dry skin induced by the administration of an EGFR inhibitor.

Adverse kidney effects of epidermal growth factor receptor inhibitors.

The epidermal growth factor receptor (EGFR) is implicated in various malignancies. The past decade has seen the development and widespread use of EGFR inhibitors for the successful treatment of such cancers. Available EGFR inhibitors include small molecule tyrosine-kinase inhibitors and monoclonal antibodies. Class-related renal adverse events result in dual toxicity including tubular/electrolyte disorders and glomerulopathies. Tubular injury is common and mainly due to monoclonal antibodies while glomerulopathy is rare and related to various anti-EGFR agents. The exact pathogenesis of anti-EGFR agents associated with kidney disorders remains to be elucidated.

A systems biology approach to understanding the function of 5T4 oncofetal glycoprotein in ovarian cancer and the preclinical effectiveness of a 5T4 antibody drug conjugate

Background5T4 is a tumour-associated antigen whose expression is associated with poor prognosis in ovarian cancer. Its expression is associated with epithelial-mesenchymal transition and modulation of cell movement via Wnt and chemokine pathways. How these pathways integrate to affect metastasis is yet to be fully elucidated. We aimed to use a systems biology approach to identify regulators of the 5T4 phenotype and evaluate the preclinical efficacy of an antibody drug conjugate (ADC) targeting 5T4 cells (5T4-ADC). Methods5T4-specific TALEN and CRISPR–Cas9 constructs were used to knock out 5T4 expression in ovarian cancer cells. Gene expression was assessed in isogenic knockout and control lines by microarray (Human Transcriptome Array 2.0 platform, Affymetrix, Santa Clara, CA, USA). 50% inhibitory concentrations (IC50) of 5T4-ADC in knockout and control cells were determined with MTS (Promega, Madison, WI, USA) and Apotox-Glo (Promega) assays. Antitumour activity of the ADC with and without carboplatin was assessed with bioluminescence imaging in SKOV3-luciferase xenografted NSG mice. FindingsComparison of the transcriptional profiles of 5T4 wild-type versus knockout SKOV3 cells identified the differential expression of 389 annotated genes (cut off p≤0·01). Network modelling of their associated pathways indicated that the epidermal growth factor receptor (EGFR) was a putative higher order regulator affecting 5T4 transcription. In vitro, IC50 was 20 times lower in SKOV3 cells expressing 5T4 when treated with 5T4-ADC than in 5T4 knockout cells. When tested against established wild-type tumours in vivo, there was a therapeutic reduction in tumour load, delayed tumour growth, and significantly increased survival compared with untreated animals (p=0·0005, log-rank test). Combining ADC treatment with carboplatin (25 mg/kg intraperitoneally) increased median survival a further 71% (IQR 142–200 days) compared with 5T4-ADC alone (IQR 88–107 days). InterpretationOur systems based approach indicates that the metastatic phenotype associated with 5T4 expression might be regulated by the activity of EGFR. The use of EGFR inhibitors in ovarian cancers has thus far shown minimal efficacy. By contrast, our preclinical data strongly support the potential for antibody targeting of drugs to ovarian cancers expressing 5T4, because this is specific, efficacious, and in combination with carboplatin can lead to longlasting regression. FundingWellcome Trust.

Patterns of practice with third-line anti-EGFR antibody for metastatic colorectal cancer.

Therapy with anti-epidermal growth factor receptor (egfr) monoclonal antibody improves outcomes for patients with metastatic colorectal cancer (mcrc) in the first-, second-, and third-line trial settings. In British Columbia, the use of egfr inhibitors (egfris) is confined to third-line therapy, which might lower the proportion of patients who receive this therapy. The objective of the present study was to describe egfri treatment patterns when those agents are limited to the third-line setting. The results will inform decisions about optimal use of egfri agents, including earlier in the course of therapy for metastatic disease. All patients with newly diagnosed mcrc who were referred to BC Cancer Agency clinics in 2009 were included in the study. Prognostic and treatment information was prospectively collected; KRAS test results were determined by chart review. The study included 443 patients with a median age of 66 years. For the 321 patients who received systemic therapy, median survival was 22.3 months. Of the 117 patients who were treated with 5-fluorouracil, oxaliplatin, and irinotecan, and who were potentially eligible for egfri therapy, 90% (105 patients) were tested for KRAS status. Of the 60 patients with KRAS wild-type tumours, 82% (49 patients) received egfri therapy. When egfri therapy is limited to the third-line setting, only a small proportion of patients receive such therapy, with death and poor performance status preventing its use in the rest. Availability of egfri in earlier lines of therapy could increase the proportion of patients treated with all active systemic agents.

Research Progress of EGFR-TKI Therapy for Patients with Central Nervous System Metastases from Non-small Cell Lung Cancer

约50%的非小细胞肺癌会出现中枢神经系统转移，从而导致不良预后。非小细胞肺癌患者中存在表皮生长因子受体（epidermal growth factor receptor, EGFR）突变，这部分患者对EGFR酪氨酸激酶抑制剂（EGFRtyrosine kinase inhibitors, EGFR-TKI）的治疗显示出了良好的耐受性及疗效。EGFR-TKI对非小细胞肺癌中枢神经系统转移也显示出了一定的疗效。本文针对EGFR-TKI药物对于非小细胞肺癌中枢神经系统转移的治疗进展进行综述。

Abstract 1182: Heparin-binding epidermal growth factor-like growth factor is a pro-differentiating factor in neuroblastoma

Abstract Neuroblastoma is the most common cancer in infancy. Current therapies are only modestly effective; patients with high-risk disease have less than a 50% chance of survival. High-risk neuroblastoma is characterized by undifferentiated neuroblasts and low Schwannian stroma content. The tumor stroma contributes to the suppression of tumor growth by releasing soluble proteins, including heparan sulfate proteoglycans (HSPGs), which act to promote neuroblast differentiation. Here we identify heparin-binding epidermal growth factor-like growth factor (HBEGF) as a potent pro-differentiating factor in neuroblastoma. Using microarray analysis, HBEGF mRNA expression is decreased in neuroblastoma compared to benign disease, correlating to an increase in mortality. HBEGF protein is expressed only in stromal compartments of tumor specimens, with tissue from high-stage disease having decreased stroma and HBEGF. Soluble HBEGF increased neuroblast differentiation and decreased proliferation, while HBEGF knockdown decreased neuroblast differentiation. In patient samples, HBEGF expression correlates with SOX10, a neural crest differentiation marker, and the cell cycle inhibitor, CDKN1A. Alternatively, HBEGF negatively correlates with ASCL1, a primitive neuroectodermal marker, and the cell cycle promoter CCND1. HSPGs, including TβRIII, GPC1, GPC3, and SDC3 further promote the differentiating effects of HBEGF treatment by forming a complex with the epidermal growth factor receptor (EGFR) via glycosaminoglycan modifications, leading to activation of the Erk1/2 pathway and upregulation of the inhibitor of DNA binding transcription factor, whose expression correlates with HBEGF in patient samples. Inhibition of EGFR with erlotinib, lapatinib, and gefitinib diminish HBEGF-induced differentiation. These data identify a novel member of the pro-differentiating secretome and support the use of heparan sulfate mimetics in neuroblastoma, while cautioning against the use of EGFR inhibitors for neuroblastoma treatment. Citation Format: Angela L. Gaviglio, Gerard C. Blobe. Heparin-binding epidermal growth factor-like growth factor is a pro-differentiating factor in neuroblastoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1182.

Functional profiling of oncogenic mutations in lung cancer patients (NCT02274025): Interim results.

e20066Background: A major advancement in the treatment of lung cancer patients is the use of EGFR inhibitors, which have shown clinical efficacy. Additionally, there are several FDA approved inhibi...

EGFR mediates hyperlipidemia-induced renal injury via regulating inflammation and oxidative stress: the detrimental role and mechanism of EGFR activation.

Previous studies have implicated inflammation, oxidative stress, and fibrosis as key factors in the development of obesity-induced kidney diseases. Epidermal growth factor receptor (EGFR) plays an important role in cancer development. Recently, the EGFR pathway has been increasingly implicated in chronic cardiovascular diseases via regulating inflammation and oxidative stress. However, it is unclear if EGFR is involved in obesity-related kidney injury. Using ApoE−/− and C57BL/6 mice models and two specific EGFR inhibitors, we investigated the potential effects of EGFR inhibition in the treatment of obesity-related nephropathy and found that EGFR inhibition alleviates renal inflammation, oxidative stress and fibrosis. In NRK-52E cells, we also elucidated the mechanism behind hyperlipidemia-induced EGFR activation. We observed that c-Src and EGFR forms a complex, and following PA stimulation, it is the successive phosphorylation, not formation, of the c-Src/EGFR complex that results in the subsequent cascade activation. Second, we found that TLR4 regulates the activation EGFR pathway mainly through the phosphorylation of the c-Src/EGFR complex. These results demonstrate the detrimental role of EGFR in the pathogenesis of obesity-related nephropathy, provide a new understanding of the mechanism behind hyperlipidemia/FFA-induced EGFR activation, and support the use of EGFR inhibitors in the treatment of obesity-induced kidney diseases.

EGFR kinase activity is required for TLR4 signaling and the septic shock response.

Mammalian Toll-like receptors (TLR) recognize microbial products and elicit transient immune responses that protect the infected host from disease. TLR4--which signals from both plasma and endosomal membranes--is activated by bacterial lipopolysaccharides (LPS) and induces many cytokine genes, the prolonged expression of which causes septic shock in mice. We report here that the expression of some TLR4-induced genes in myeloid cells requires the protein kinase activity of the epidermal growth factor receptor (EGFR). EGFR inhibition affects TLR4-induced responses differently depending on the target gene. The induction of interferon-β (IFN-β) and IFN-inducible genes is strongly inhibited, whereas TNF-α induction is enhanced. Inhibition is specific to the IFN-regulatory factor (IRF)-driven genes because EGFR is required for IRF activation downstream of TLR--as is IRF co-activator β-catenin--through the PI3 kinase/AKT pathway. Administration of an EGFR inhibitor to mice protects them from LPS-induced septic shock and death by selectively blocking the IFN branch of TLR4 signaling. These results demonstrate a selective regulation of TLR4 signaling by EGFR and highlight the potential use of EGFR inhibitors to treat septic shock syndrome.

Determination of EGFR and KRAS mutational status in Greek non-small-cell lung cancer patients.

It has been reported that certain patients with non-small-cell lung cancer (NSCLC) that harbor activating somatic mutations within the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene may be effectively treated using targeted therapy. The use of EGFR inhibitors in patient therapy has been demonstrated to improve response and survival rates; therefore, it was suggested that clinical screening for EGFR mutations should be performed for all patients. Numerous clinicopathological factors have been associated with EGFR and Kirsten-rat sarcoma oncogene homolog (KRAS) mutational status including gender, smoking history and histology. In addition, it was reported that EGFR mutation frequency in NSCLC patients was ethnicity-dependent, with an incidence rate of ~30% in Asian populations and ~15% in Caucasian populations. However, limited data has been reported on intra-ethnic differences throughout Europe. The present study aimed to investigate the frequency and spectrum of EGFR mutations in 1,472 Greek NSCLC patients. In addition, KRAS mutation analysis was performed in patients with known smoking history in order to determine the correlation of type and mutation frequency with smoking. High-resolution melting curve (HRM) analysis followed by Sanger sequencing was used to identify mutations in exons 18–21 of the EGFR gene and in exon 2 of the KRAS gene. A sensitive next-generation sequencing (NGS) technology was also employed to classify samples with equivocal results. The use of sensitive mutation detection techniques in a large study population of Greek NSCLC patients in routine diagnostic practice revealed an overall EGFR mutation frequency of 15.83%. This mutation frequency was comparable to that previously reported in other European populations. Of note, there was a 99.8% concordance between the HRM method and Sanger sequencing. NGS was found to be the most sensitive method. In addition, female non-smokers demonstrated a high prevalence of EGFR mutations. Furthermore, KRAS mutation analysis in patients with a known smoking history revealed no difference in mutation frequency according to smoking status; however, a different mutation spectrum was observed.

Tumor-derived TGF-β and prostaglandin E2 attenuate anti-tumor immune responses in head and neck squamous cell carcinoma treated with EGFR inhibitor

BackgroundEGFR-targeted therapy is an attractive option for head and neck squamous cell carcinoma patients. We have recently reported the use of EGFR inhibitors as an adjunct treatment to enhance HLA-DR expression in tumor cells to improve cancer immunotherapy. Nevertheless, we observed that EGFR inhibitors resulted in decreased anti-tumor responses, regardless of upregulation of HLA-DR expression on the tumor cell. In this study, we specifically investigated the mechanisms by which EGFR inhibition modulated anti-tumor responses.MethodsAn EGFR inhibitor erlotinib was used to assess the modulation of anti-tumor responses by tumor antigen-specific helper T cells. We then examined whether administration of the EGFR inhibitor altered tumor cytokine profiles and expression of immune-related molecules on tumor cells.ResultsDespite the augmented HLA-DR expression on a gingival cancer cell line by EGFR inhibition, anti-tumor responses of EGFR reactive helper T cell clones against tumor cells were decreased. EGFR inhibition did not change the expression of CD80, CD86, or PD-L1 on the tumor cells. Conversely, production of transforming growth factor beta (TGF-β) and prostaglandin E2 was increased by EGFR inhibition, indicating that these immunosuppressive molecules were involved in diminishing tumor recognition by T cells. Significantly, attenuation of HTL responses against tumors after EGFR inhibition was reversed by the addition of anti-TGF-β antibody or COX2 inhibitors.ConclusionsTargeting TGF-β and prostaglandin E2 may allow for improved outcomes for cancer patients treated with combination immunotherapy and EGFR inhibitors.

Systemic sclerosis immunoglobulin induces growth and a pro-fibrotic state in vascular smooth muscle cells through the epidermal growth factor receptor.

ObjectiveIt has been suggested that autoantibodies in systemic sclerosis (SSc) may induce the differentiation of cultured fibroblasts into myofibroblasts through platelet-derived growth factor receptor (PDGFR) activation. The present study aims to characterize the effects of SSc IgG on vascular smooth muscle cells (VSMCs) and to determine if stimulatory autoantibodies directed to the PDGFR can be detected, and whether they induce a profibrotic response in primary cultured VSMCs.MethodsCultured VSMCs were exposed to IgG fractions purified from SSc-patient or control sera. VSMC responses were then analyzed for ERK1/2 and Akt phosphorylation, PDGFR immunoprecipitation, cellular proliferation, protein synthesis, and pro-fibrotic changes in mRNA expression.ResultsStimulatory activity in IgG fractions was more prevalent and intense in the SSc samples. SSc IgG immunoprecipitated the PDGFR with greater avidity than control IgG. Interestingly, activation of downstream signaling events (e.g. Akt, ERK1/2) was independent of PDGFR activity, but required functional EGFR. We also detected increased protein synthesis in response to SSc IgG (p<0.001) and pro-fibrotic changes in gene expression (Tgfb1 +200%; Tgfb2 −23%; p<0.001)) in VSMCs treated with SSc IgG.ConclusionWhen compared to control IgG, SSc IgG have a higher stimulation index in VSMCs. Although SSc IgG interact with the PDGFR, the observed remodeling signaling events occur through the EGFR in VSMC. Our data thus favour a model of transactivation of the EGFR by SSc-derived PDGFR autoantibodies and suggest the use of EGFR inhibitors in future target identification studies in the field of SSc.

EGFR Inhibition in the Treatment of Squamous Cell Carcinoma of the Head and Neck

Squamous cell carcinoma of the mucosal surfaces in the head and neck (SCCHN) remains a therapeutic challenge in much of the world. Most patients present with locally and/or regionally advanced disease, and are offered curative (definitive) therapy in the form of external beam radiotherapy with a concurrent radiosensitizing systemic agent, most commonly platinum-based or targeting an epidermal growth factor receptor (EGFR). In this review, we will cover the literature and published data evaluating the use of EGFR inhibitors as part of the concurrent or postoperative regimen in the context of definitive treatment for patients with SCCHN, as well as its use in patients with recurrent or distantly metastatic disease.

Histopathology of acneiform eruptions in patients treated with epidermal growth factor receptor inhibitors

Epidermal growth factor receptor inhibitors (EGFRIs) are anticancer agents that have been approved for use in a variety of solid tumors. EGFR-inhibiting agents produce a variety of cutaneous adverse events: most commonly a follicular papulopustular (acneiform) eruption on the face, scalp, chest and upper back. The goal of this manuscript is to elucidate the histopathologic findings associated with this most common adverse event. The histopathological findings of 10 patients with papulopustular eruptions induced by EGFRIs are described and compared to the four prior published case series of acneiform rashes attributed to EGFRIs. All 10 patients in our case series showed a superficial, predominantly neutrophilic suppurative folliculitis with ectatic follicular infundibula and rupture of the epithelial lining. Similar pathology was found in the four other case series discussing this phenomenon. While the characteristic clinical appearance of this rash precludes the need for a biopsy in most cases, this knowledge promotes our understanding of the pathophysiologic process. As the use of EGFRIs expands, dermatopathologists will see these reactions more commonly and will need to recognize this pattern.

Cost-effective analysis of the use of EGFR inhibitors (E) for wild-type (WT) KRAS unresectable metastatic colorectal cancer (mCRC).

6552 Background: Patients (pts) with unresectable WT KRAS mCRC benefit from fluoropyrimidines (FP), oxaliplatin (O), irinotecan (I), bevacizumab (Bev) and E. The most cost-effective strategy to combine them remains unclear. Methods: A Markov model was constructed for a hypothetical cohort of pts with mCRC to examine the costs and outcomes of 3 treatment strategies: (A): 1st line (1L) Bev+FP+O/I, 2nd line (2L) FP+I/O, 3rd line (3L) E, (B): 1L Bev+FP+O/I, 2L FP+I/O, 3L E+I, and (C): 1L E+FP+O/I, 2L Bev+FP+I/O, 3L best supportive care (BSC). Efficacy and probability data of the treatments were obtained from clinical trials identified through a systematic review of the literature. Resource utilization data were derived from a chart review of 65 consecutive pts treated at Odette Cancer Centre (OCC) since 2009 and from the literature. Utilities were obtained by surveying oncologists (n= 24) across Canada using EQ-5D. Costs were obtained from the Ontario Ministry of Health and Long/Term Care, Ontario Case Costing Initiative, OCC and the literature. The analysis was conducted from the Canadian public healthcare system perspective over a 5 year time horizon with a 5% discount in 2012 Canadian dollars (CAD$) for cost and outcome. Incremental cost-effectiveness analyses were conducted comparing costs and outcomes of the 3 strategies. One way and probabilistic sensitivity analyses (SA) were conducted (n=10,000). Results: All 3 strategies appeared to be of relatively similar efficacy clinically, but C is more expensive than A or B by &gt;45% (see Table). The model is primarily driven by the acquisition cost of drugs. B is most cost-effective when the willingness-to-pay (WTP) threshold &gt;$120,000/QALY. SA showed that C would be cost-effective only when the progression-free survival of E is better than Bev in 1L with hazard ratio &lt;0.24 at WTP of $150,000/QALY. Conclusions: 1L use of E followed by 2L Bev in mCRC is not cost-effective at the current pricing of E relative to Bev. [Table: see text]

Epidermal Growth Factor and Epidermal Growth Factor Receptor: The Yin and Yang in the Treatment of Cutaneous Wounds and Cancer

Epidermal growth factor (EGF) and EGF receptor (EGFR) play an essential role in wound healing through stimulating epidermal and dermal regeneration. The development of new therapies for enhancing wound healing has included the use of EGF. In addition, EGFR inhibitors (EGFRis) have become a therapeutic option for the treatment of cancer. Thus, therapies targeting EGF/EGFR are useful for the treatment of both cutaneous wounds and cancer. Identification of EGFR as a regulator of normal and pathological cell function has allowed for the development of EGFRis for the treatment of cancer and topical administration of EGF to enhance wound healing. The use of EGFRi has emerged as an option for metastatic cancers. These drugs induce dermatological toxicity, a papulopustular rash that is pruritic and painful; chronic use may negatively impact wound healing. Currently, there is no standard therapy to alleviate the side effects caused by EGFRi administration except to reduce or eliminate EGFRi usage. Therefore, side effects from these drugs should be taken into consideration on patients prone to develop chronic wounds and with cutaneous injuries. There is a need for adjunctive treatment to eliminate dermatological toxicity from EGFRi use. The development of new downstream targets of EGFR may be a rational strategy to reduce potential cutaneous side effects and provide a better strategy for the treatment of cancer. Until then, the topical use of EGF could be used to ameliorate dermatological lesions caused by EGFRi.