Epidermal Growth Factor Receptor Inhibitors Treatment Research Articles

Egfri-Induced Skin Folliculitis Presenting on the Scalp: A Case Report

Skin toxicity, or folliculitis, is the most common adverse side effect resulting from the use of antineoplastic signal transduction inhibitors like the epidermal growth factor receptor inhibitors (EGFRI) panitumumab and poziotinib. This condition takes a toll on a patient’s quality of life and can affect up to 90% of patients. Moreover, it is one of the primary contributing factors to the patient’s decision to discontinue antineoplastic therapy, thus highlighting the need for better dermatologic interventions to help mitigate the side effects resulting from EGFRI treatment. We present the case of a 76-year-old female patient who presented with a sudden, severe folliculitis exclusively affecting her scalp following years of stable tumor suppressor therapy

Reducing Acneiform Rash Induced by EGFR Inhibitors With Honeysuckle Therapy: A Prospective, Randomized, Controlled Study.

Background: Epidermal growth factor receptor inhibitors (EGFRIs), including cetuximab, erlotinib, gefitinib and icotinib, have been proven to be effective in treating colorectal cancer or lung cancer. However, most of patients who receive EGFRIs treatment experience cutaneous toxicities, such as acneiform or papulopustular rashes, which affects quality of life and leads to discontinuation of cancer therapies. Honeysuckle is a traditional herb historically used to treat skin rash for thousands of years in Eastern Asia and showed proven safety in human. Methods: To investigate whether honeysuckle therapy could control EGFRIs induced acneiform rashes, a total of 139 colorectal and lung cancer patients with EGFRIs treatments were recruited in a prospective study. Patients were randomized to 3 arms (Arm A: prophylactic treatment with honeysuckle before rash occurred; Arm B: symptomatic treatment with honeysuckle when rash occurred; Arm C: conventional treatment with minocycline and a topical solution when rash occurred). The incidences, severities and recovery time of acneiform rash were observed in each arm. Results: Honeysuckle treatment reduced incidences of EGFRIs induced acneiform rash, which were 56.5, 68.1 and 71.7% in Arm A, B and C, respectively (p = 0.280). Severities of rash (CTCAE grade 2 and 3) were significantly lower in prophylactic honeysuckle treatment (Arm A) compared to conventional treatment (Arm C) (p = 0.027), which was 10–21%, respectively. Patients with honeysuckle treatment recovered more quickly from pruritus, the median time was 22, 36 and 58 days in Arm A, B and C, respectively (p = 0.016). Conclusion: Honeysuckle was effective in reducing incidences and severities of EGFRIs induced acneiform rash, especially for prophylactic treatment.

Prevention and treatment of mucocutaneous adverse reactions associated with epidermal growth factor receptor inhibitors

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.

The trichoscopic features of hair shaft anomalies induced by epidermal growth factor receptor inhibitors: A case series

Although the clinical hair changes that occur under treatment with epidermal growth factor receptor inhibitors (EGFRIs) are documented, their trichoscopic features have not been reported. To evaluate the trichoscopic findings in scalp and facial hair, induced by EGFRI treatment. Patients treated with EGFRIs at a tertiary oncodermatology clinic in 2015 through 2017 were evaluated for macroscopic and trichoscopic changes. The cohort included 23 patients (13 women; median age, 68years) treated with EGFRIs for an average of 13months (range, 2-40months). Macroscopically, 18 patients (78%) had dry, lusterless, coarse, kinky, brittle scalp hair, and 17 (74%) had trichomegaly of the eyebrows/eyelashes. Trichoscopic findings were of hair shaft anomalies including pili torti, affecting scalp hair in 20 patients (87%), eyebrows in 6 (26%), and eyelashes in 8 (50%), and asymmetric hyperpigmented fusiform widening of hair scalp in 3 (13%), eyebrows in 10 (43%), and eyelashes in 4 (25%). Dermoscopic findings of the peri- and interfollicular skin were scale, whitish erythematous structureless areas, and branching vessels. Lack of trichoscopic-histologic correlation, lack of baseline examination. The trichoscopic correlates of the macroscopic hair changes under EFGRI treatment include pili torti, and asymmetric hyperpigmented fusiform widening, with dermoscopic cutaneous manifestations of scale, whitish erythematous structureless areas, and branching vessels.

Ocular surface adverse events of systemic epidermal growth factor receptor inhibitors (EGFRi): A prospective trial

Controversy exists regarding the safety of agents that systemically inhibit epidermal growth factor receptor (EGFRi) in oncologic patients in terms of toxicity to the ocular surface. We performed a prospective clinical study comparing the ocular surface toxicity of systemic EGFRi between a case and a control group. Patients with lung or colon cancer were divided in two groups: 25 patients treated with systemic EGFRi and 25 control patients without EGFRi treatment. Patients in both groups were chemotherapy naive. Four visits were scheduled in a one year period comparing signs and symptoms in terms of symptom questionnaires (SIDEQ, OSDI and AVS), corneal fluorescein staining (Oxford test), tear production (Schirmer's test) and a quantitative evaluation of conjunctival chemosis and hyperemia. Basal epithelial cell density (CEBD) and corneal subepithelial nerve fiber density (CNFD) were measured and compared using confocal microscopy (Heidelberg Engineering, Germany). The differences in each variable were compared with the analysis of variance (ANOVA). A P value<0.05 was considered significant for all comparisons. No statistically significant differences were found between patients under EGFRi treatment and the age-matched controls in the variables analyzed. When cases and controls were evaluated separately, the case group showed a significantly worse progression of signs (chemosis score, CFS, Schirmer's) as well as in terms of CEBD and CNFD (all P<0.05). Systemic EGFRi may increase dry eye signs as well as decrease CEBD and CNFD. This study may help us to understand the true toxicity of EGFRi to the ocular surface.

Epidermal Growth Factor Receptor Inhibitor Skin Rash Prophylaxis in a Community Oncology Setting

Epidermal growth factor receptor inhibitors (EGFRIs) can potentially cause a debilitating rash despite use of reactive-based treatment. Prophylactic rash management is a controversial rash-mitigating approach. The impact of a prophylactic rash treatment protocol for EGFRIs at a community hospital was evaluated. This was a retrospective, institutional review board-approved examination of patient data for those patients who received EGFRIs from August 1, 2012, through May 31, 2015. Patients were grouped according to treatment with EGFRIs prior to standardized prophylactic rash management protocol (August 1, 2012, through July 31, 2014) and treatment after protocol implementation (September 1, 2014, through May 31, 2015). The outcomes measured included incidence of rash within the 6-week treatment period and occurrence of EGFRI dose reductions and/or delays. Of the 44 patients eligible for the analysis, 29 were evaluated in the reactive treatment group and 15 in the rash prophylaxis group. The incidence of rash over the 6-week EGFRI treatment period was 76% and 47% for the reactive treatment and rash prophylaxis groups, respectively (p = .09). There was a lower incidence of EGFRI dose delays and modifications in the rash prophylaxis group compared to the reactive treatment group: 26.7% and 6.7% compared to 41.4% and 20.7%, respectively. There was an overall decrease in rash incidence seen in patients who received prophylactic intervention; however, due to the failure to meet statistical significance and power, it is not possible to determine if rash prophylaxis decreases EGFRI rash incidence.

MET Gene Amplification and MET Receptor Activation Are Not Sufficient to Predict Efficacy of Combined MET and EGFR Inhibitors in EGFR TKI-Resistant NSCLC Cells.

Epidermal growth factor receptor (EGFR), member of the human epidermal growth factor receptor (HER) family, plays a critical role in regulating multiple cellular processes including proliferation, differentiation, cell migration and cell survival. Deregulation of the EGFR signaling has been found to be associated with the development of a variety of human malignancies including lung, breast, and ovarian cancers, making inhibition of EGFR the most promising molecular targeted therapy developed in the past decade against cancer. Human non small cell lung cancers (NSCLC) with activating mutations in the EGFR gene frequently experience significant tumor regression when treated with EGFR tyrosine kinase inhibitors (TKIs), although acquired resistance invariably develops. Resistance to TKI treatments has been associated to secondary mutations in the EGFR gene or to activation of additional bypass signaling pathways including the ones mediated by receptor tyrosine kinases, Fas receptor and NF-kB. In more than 30–40% of cases, however, the mechanisms underpinning drug-resistance are still unknown. The establishment of cellular and mouse models can facilitate the unveiling of mechanisms leading to drug-resistance and the development or validation of novel therapeutic strategies aimed at overcoming resistance and enhancing outcomes in NSCLC patients. Here we describe the establishment and characterization of EGFR TKI-resistant NSCLC cell lines and a pilot study on the effects of a combined MET and EGFR inhibitors treatment. The characterization of the erlotinib-resistant cell lines confirmed the association of EGFR TKI resistance with loss of EGFR gene amplification and/or AXL overexpression and/or MET gene amplification and MET receptor activation. These cellular models can be instrumental to further investigate the signaling pathways associated to EGFR TKI-resistance. Finally the drugs combination pilot study shows that MET gene amplification and MET receptor activation are not sufficient to predict a positive response of NSCLC cells to a cocktail of MET and EGFR inhibitors and highlights the importance of identifying more reliable biomarkers to predict the efficacy of treatments in NSCLC patients resistant to EGFR TKI.

Preemptive Management of Dermatologic Toxicities Associated With Epidermal Growth Factor Receptor Inhibitors

Epidermal growth factor receptor inhibitors (EGFRIs) are a treatment option for patients diagnosed with advanced-stage gastrointestinal, lung, and head and neck cancers. The most prevalent complications associated with EGFRIs are dermatologic toxicities, which may result in either disruption or discontinuation of treatment and adversely affect patients' quality of life. Nurses play a vital role in educating patients about EGFRI-related dermatologic toxicities; therefore, nurses must continue to educate themselves on the various aspects of EGFRI treatment. An overview of the EGF signaling pathway is provided, and dermatologic toxicities associated with EGFRI treatment are described. A review of several studies evaluating reactive skin treatment regimens also are discussed. Nurses play a critical role in providing patient support. Informing patients about potential EGFRI-related symptoms and dermatologic toxicities will help prepare patients for their course of treatment. In addition, nurses should provide patients with a variety of coping strategies to help manage dermatologic toxicities that will assist in enhancing patients' adherence to EGFRI treatment.

Development of a functional assessment of chronic illness therapy questionnaire to assess dermatology-related quality of life in patients treated with EGFR inhibitors: FACT-EGFRI.

9046 Background: Dermatologic toxicities (dT) to epidermal growth factor receptor inhibitors (EGFRI) are common and impact quality of life (QoL), which may lead to dose reduction or discontinuation of anticancer therapy. Currently, there are no patient reported outcomes measures (PRO) that assess QoL related to dT from EGFRI treatment. This study describes the development of a PRO questionnaire for dT to EGFRI. Methods: A three-phase process was utilized for item generation, reduction and scale construction. First, a comprehensive literature review was performed and all questions with potential relevance for patients with dT were selected for further evaluation in the form of 62 EGFRI-dT specific items, including some from dermatologic QoL instruments such as the Skindex. Next, a survey and evaluation of these potential items by 12 dT expert physicians and nurses and 20 patients was completed. Finally, the pilot questionnaire was administered to 24 patients with various stages of dT. Item comprehension, relevance and overall content was assessed in semi- structured interviews. Results: In qualitative interviews, patients and experts evaluated the importance of 62 items from the literature and the Skindex. Comments and response frequencies were summarized. Items identified as “quite relevant” or “very relevant” by the majority of experts were retained. Item review and reduction resulted in a 38-item pilot questionnaire. A majority of patients determined the content of the pilot questionnaire to be relevant, comprehensive and easy to understand. Patient input resulted in the omission of 3 items, modification of 6 items, and the addition of 4 items. Final revisions resulted in the FACT-EGFRI, consisting of 18 items encompassing well-being in 3 QoL domains: physical (7 items), social/emotional (6 items), and functional (5 items). Conclusions: The face and content validity of the FACT-EGFRI has been confirmed by EGFRI-dT patients and professionals. Formal validation and reliability testing is planned in a prospective cohort of EGFRI-induced patients with all dT severity grades. The FACT-EGFRI is available at www.facit.org. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, Genentech, ImClone Systems, Onyx Amgen, Bayer, Bristol-Myers Squibb, ImClone Systems, Onyx Hana Biosciences

KRAS Mutation in Colon Cancer: A Marker of Resistance to EGFR-I Therapy

Introduction and DesignThe introduction of the epidermal growth factor receptor inhibitors (EGFR-I) has increased the treatment options available for patients with metastatic colorectal cancer (mCRC). Two EGFR-I agents currently approved for the treatment of mCRC are the fully human monoclonal antibody panitumumab and the mouse-human chimeric monoclonal antibody cetuximab. While these agents have demonstrated activity across multiple lines of therapy, early studies suggested that clinical benefit was confined to a subset of patients treated. Mutation of the KRAS oncogene has emerged as a powerful negative predictive biomarker to identify patients with mCRC who do not benefit from EGFR-I therapy. Multiple retrospective analyses have demonstrated that clinical benefit from treatment with EGFR-I is limited to patients with tumors harboring the wild-type KRAS gene. In this review, the KRAS pathway and studies evaluating KRAS as a prognostic marker in CRC are discussed along with advances in KRAS gene mutation testing. Clinical trials evaluating the role of KRAS status in response to EGFR-I monotherapy or in combination with chemotherapy are also highlighted along with ongoing studies evaluating the role of EGFR-I treatment on curative resections rates.Results and ConclusionFuture studies investigating EGFR-I therapy in mCRC should incorporate KRAS mutation testing into the study protocol in order to more accurately determine the patient population that will obtain clinical benefit from these novel agents.

Cutaneous side-effects in patients on long-term treatment with epidermal growth factor receptor inhibitors

Acute and subacute cutaneous side-effects of epidermal growth factor receptor inhibitors (EGFRIs) are very frequent and well known. Much less is known about the chronic cutaneous effects of these drugs and about their potential psychosocial impact on patients. We performed a retrospective study of patients treated with EGFRIs for more than 6 months. All patients had a detailed dermatological examination. The primary cancer, associated chemotherapies, skin treatment, evolution of skin symptoms and their impact on quality of life (QoL) as evaluated by the Dermatology Life Quality Index (DLQI) were noted. Seven men and nine women were identified. The mean length of EGFRI treatment was 10 months (range 6-27). At the time of examination, all patients (100%) had cutaneous side-effects. Grade I or II folliculitis was found in 37.5% of the patients. Additional skin manifestations were xerosis (100%), mucositis (69%), hair abnormalities (87.5%), eyelash trichomegaly (62.5%), facial hypertrichosis (56%), painful paronychia (56%) and onycholysis (44%). Dose reduction or EGFRI discontinuation for skin toxicity were needed in six patients (37.5%). DLQI evaluation showed a moderate to strong impact on QoL in four patients (25%). Cutaneous side-effects are found in 100% of patients treated with EGFRIs for more than 6 months and have a significant effect on patients' QoL. The clinical spectrum of skin manifestation varies over time. As the use of EGFRIs rapidly increases, it is critical for us to improve our knowledge in the understanding and managment of these skin manifestations.