Elevated expression of ISY1, APOA-1, SYNE1, MTG1, and MMP10 at HCC initiation: HCC specific protein network involving interactions of key regulators of lipid metabolism, EGFR signaling, MAPK, and splicing pathways.

Identification of molecular regulators of hepatocellular carcinoma (HCC) initiation and progression is not well understood. We chemically induced HCC in male Wistar rats by administration of diethyl nitrosamine (DEN) and 2-acetylaminofluorene (2-AFF). Using 2D-electrophoresis and MALDI-TOF-MS/MS analyses, we characterized differentially expressed proteins in liver tissues at early stage of HCC progression. Using RT-PCR analysis, we quantified the mRNA expression of the characterized proteins and validated the transcript expression with tumor tissues of clinically confirmed HCC patients. Using bioinformatic tools, we analyzed a network among the introduced proteins that identified their interacting partners and analyzed the molecular mechanisms associated with signaling pathways during HCC progression. We characterized a protein, namely, pre-mRNA splicing factor 1 homolog (ISY1), which is upregulated at both transcriptome and proteome levels at HCC initiation, progression, and tumor stages. We analyzed the interacting partners of ISY1, namely, APOA-1, SYNE1, MMP10, and MTG1. Real-time PCR analysis confirmed elevated expression of APOA-1 mRNA at HCC initiation, progression, and tumor stages in animals undergoing tumorigenesis. The mRNA expression of the interacting partners was validated with tumor tissues of clinically confirmed liver cancer patients; the analysis revealed significant elevation in expression of transcripts. The transcriptome and proteome analyses complement each other and dysregulation in mRNA and protein expression of these regulators may play critical role in HCC initiation and progression.

METTL1-m7 G-EGFR/EFEMP1 axis promotes the bladder cancer development.

BACKGROUND: The posttranscriptional modifications of transfer RNA (tRNA) are critical for all aspects of the tRNA function and have been implicated in the tumourigenesis and progression of many human cancers. By contrast, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7 G tRNA modification in bladder cancer (BC) remain obscure. RESULTS: In this research, we show that METTL1 was highly expressed in BC, and its level was correlated with poor patient prognosis. Silencing METTL1 suppresses the proliferation, migration and invasion of BC cells in vitro and in vivo. Multi-omics analysis reveals that METTL1-mediated m7 G tRNA modification altered expression of certain target genes, including EGFR/EFEMP1. Mechanistically, METTL1 regulates the translation of EGFR/EFEMP1 via modifying certain tRNAs. Furthermore, forced expression of EGFR/EFEMP1 partially rescues the effect of METTL1 deletion on BC cells. CONCLUSIONS: Our findings demonstrate the oncogenic role of METTL1 and the pathological significance of the METTL1-m7 G-EGFR/EFEMP1 axis in the BC development, thus providing potential therapeutic targets for the BC treatment.

Immuno-toxicological evaluation of her1 cancer vaccine in non-human primates: a 6-month subcutaneous study.

Purpose: A vaccine composition based on the extracellular domain of the human epidermal growth factor receptor 1 (HER1-ECD) and the combination of VSSP (very small size proteoliposomes) and Montanide ISA 51 adjuvants when used by intramuscular route, demonstrated promising results in preclinical studies. However, in order to avoid potential adverse events due to the use of Montanide, it is proposed to modify the vaccine formulation by using VSSP (very small size proteoliposomes) adjuvant alone, and to evaluate the quality of subcutaneously induced immune response. This study aimed to assess the immunotoxicological effects of HER1 vaccine in Cercopithecus aethiops.Materials and methods: Fifteen monkeys were randomized into four groups: Negative Control (Tris/NaCl, s.c.), Positive Control (200 µg HER1-ECD/VSSP/Montanide ISA-51 VG, i.m), Low Dose (200 µg HER1-ECD/VSSP/Tris NaCl, s.c.) and High Dose (800 µg HER1-ECD/VSSP/Tris NaCl, s.c). All monkeys received 7 doses and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study, and electrocardiographical and ophthalmological studies were performed. Humoral and cellular immune response and clinical pathology parameters were analyzed.Results: Animal's survival in the study was 100% (n = 15). Administration site reactions were observed in the Positive Control animals (n = 4). HER1 vaccine administered subcutaneously (High Dose Group) achieved good IgG antibody titers although lower than the Positive Control group, but with higher ability to inhibit HER1 phosphorylation. Conclusions: This suggests that the alternative of eliminating the use of Montanide in the HER1 vaccine preparation and the using subcutaneous route is feasible.

Clinical impact of rebiopsy among patients with epidermal growth factor receptor-mutant lung adenocarcinoma in a real-world clinical setting.

BACKGROUND: In this study, we investigated the risk factors of acquired T790M mutation among patients with lung adenocarcinoma with epidermal growth factor receptor (EGFR) tyrosine mutation who were treated with EGFR-tyrosine kinase inhibitors (TKIs). The aim was to identify the clinical impact of rebiopsy. METHODS: This multicenter, retrospective cohort study was conducted in South Korea from January 2007 to June 2017. Patients with adenocarcinoma with EGFR mutation who underwent rebiopsy and were treated with EGFR-TKIs were included. RESULTS: Of a total of 352 patients, T790M mutation was identified in 156 (41.9%) at the time of rebiopsy. The median duration from initial biopsy to rebiopsy was 17 months. Univariate logistic regression analysis revealed associations of exon 19 deletion (odds ratio [OR], 1.643; p = 0.026), absence of L858R (OR, 0.627; p = 0.042), and previous EGFR-TKI treatment duration (OR, 1.039; p < 0.001) with T790M mutation. Previous EGFR-TKI treatment duration (OR, 3.580; p < 0.001) was independently associated with T790M mutation. A multivariate Cox proportional hazard model revealed that brain metastasis at initial diagnosis (hazard ratio, 1.390; p = 0.050) tended to be associated with T790M mutation. Among the patients with T790M mutation at rebiopsy, the osimertinib user group (n = 90) had a better one-year survival (68.7 vs. 58.3%, p = 0.048) than the osimertinib nonuser group (n = 66). CONCLUSIONS: Rebiopsy might affect the clinical course of patients with EGFR-mutant adenocarcinoma who receive EGFR-TKIs.

Incidence of Adverse Cutaneous Reactions to Epidermal Growth Factor Receptor Inhibitors in Patients with Non-Small-Cell Lung Cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) inhibitors are routinely used in advanced non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, their use is associated with gastrointestinal and cutaneous toxicities, including acneiform eruptions, pruritus, xerosis, nail and hair changes. Aside from reducing patients' quality of life, such cutaneous reactions have a considerable impact on the oncologic treatment given that dose reduction or even drug discontinuation may be necessary, especially for the severe forms. OBJECTIVES: To assess the incidence, impact on treatment and management of EGFR inhibitor-related cutaneous reactions in patients with NSCLC. METHODS: We conducted a prospective observational study on 87 consecutive patients with advanced NSCLC treated with EGFR-tyrosine kinase inhibitors from January to December 2019. Patients who developed mucocutaneous reactions were evaluated and treated by both oncologists and dermatologists, and underwent dermatologic follow-up until resolution of the cutaneous reaction. Demographic and clinical data were collected for each patient, and the severity of the cutaneous reaction was graded using the Common Terminology Criteria for Adverse Events. RESULTS: Seventy-one patients (81.6%) developed cutaneous reactions. The number of cutaneous reactions per patient was 1 in 37%, 2 in 41% and 3 or more in 22%. The most common cutaneous reactions included acneiform eruptions (56.3%), xerosis ± asteatotic eczema (48.3%), nail changes (39.1%), mucositis (29.9%), pruritus (24.1%) and hair changes (12.6%). Afatinib was associated with a higher rate of nail changes and mucositis (p < 0.01 and p < 0.005, respectively) compared to other agents, while no patient-related predictive factors were identified. Dose reduction was performed in 18% of patients. Multidisciplinary management involving dermatologists allowed to resume the drug in all patients who had discontinued it due to the cutaneous reactions. CONCLUSIONS: A multidisciplinary approach to EGFR inhibitor-related cutaneous reactions is advantageous and can reduce the need to discontinue oncologic treatment.

Prophylactic Topical Treatment for EGFR Inhibitor-Induced Papulopustular Rash: A Randomized Clinical Trial.

BACKGROUND: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%. OBJECTIVE: To investigate prophylactic topical treatment for EGFRI-induced rash. METHODS: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions. RESULTS: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA. CONCLUSIONS: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash.

Anti-EGFR Single-Chain Fv Antibody Fragment Displayed on the Surface of Ferritin H-Chain Protein Nanoparticle for Asthma Therapy.

Epidermal growth factor receptor (EGFR)-dependent signaling contributes to the pathophysiology of asthma. However, these findings have not been translated into a clinical application. We recently generated ferritin H-chain protein (FTH1)-based nanoparticles with an anti-EGFR single-chain Fv (anti-EGFR scFv) on the surface of FTH1, namely, anti-EGFR scFv-FTH1/FTH1 nanoparticles. In the present study, we found that these nanoparticles could specifically bind to EGFR-expressing cells, leading to downregulation of EGFR and mucin 5AC (MUC5AC) protein expression and growth suppression of House Dust Mite (HDM)-stimulated human bronchial epithelial 16HBE and lipopolysaccharides (LPS)-activated murine macrophage-like RAW264.7 cells. In vivo, intraperitoneal administration of anti-EGFR scFv-FTH1/FTH1 nanoparticles, but not FTH1 nanoparticles, alleviated the major pathological symptoms including airway hyperresponsiveness, airway inflammation, goblet cell hyperplasia, mucus hyperproduction, and increased release of Th2 cytokines in an allergen ovalbumin (OVA)-induced asthma mouse model. Importantly, during the dosing period these nanoparticles were safe for both heathy and asthmatic mice, and more effective in controlling airway inflammation than cetuximab, an EGFR monoclonal antibody. Altogether, our studies provide insights into the control of airway inflammation for treatment of asthma by targeting EGFR. The similar strategy can be used to fabricate scFv-based recombinant protein nanoparticles for other clinical applications.

The effects of switching EGFR-TKI treatments for non-small cell lung cancer because of adverse events.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used to treat patients with non-small cell lung cancer (NSCLC) and EGFR driver mutations. Although some patients discontinued these treatments because of adverse events, it is unclear whether switching EGFR-TKI because of adverse events provides a benefit. METHODS: This retrospective study evaluated data from 22 patients with EGFR mutation-positive NSCLC who received at least two EGFR-TKIs that were switched because of adverse events (March 2011 to September 2017). Progression-free survival 2 (PFS2) was defined as the time from starting of the first EGFR-TKI treatment to disease progression during the second EGFR-TKI treatment. RESULTS: Seventeen patients received gefitinib as the first EGFR-TKI treatment, while four patients received afatinib and one patient received erlotinib. The median time to failure of the first EGFR-TKI treatment was 1.6 months. The EGFR-TKIs were switched because of hepatotoxicity (n = 16), interstitial lung disease (n = 3), and other reasons (n = 3). The median washout period was 1.1 months. Seventeen patients received erlotinib as the second EGFR-TKI treatment, while three patients received gefitinib and two patients received afatinib. The median PFS for the second EGFR-TKI treatment was 15.2 months. The median PFS2 was 17.7 months and the median overall survival was 32.8 months. CONCLUSIONS: Switching EGFR-TKIs because of adverse events provided a clinical benefit for patients with EGFR mutation-positive NSCLC. Appropriate judgment regarding switching from one EGFR-TKI to another may improve the performance status and prognosis of patients with EGFR mutation-positive NSCLC.

Cutaneous toxicities of epidermal growth factor receptor inhibitors: A prospective study in 60 Asian patients.

BACKGROUND: Several prospective studies have been conducted in epidermal growth factor receptor (EGFR) inhibitor-related cutaneous reactions in Caucasian patients, but prospective studies in Asian populations are scarce. OBJECTIVE: To investigate the cutaneous side effects of EGFR inhibitors in Asian cancer patients and to assess tumor response to dermatologic manifestations. METHODS: Sixty patients with lung or colorectal cancer who were receiving EGFR inhibitors were prospectively followed for at least one year by oncologists and dermatologists. RESULTS: Of 60 patients (33 males, 27 females), 46 lung cancer patients received erlotinib (n=29) and gefitinib (n=17). Cetuximab was prescribed in 14 colorectal cancer patients. Fifty-eight patients (58/60, 96.7%) developed cutaneous reactions. The most common reactions were xerosis (82.8%), acne (79.3%), and skin desquamation (62.1%). Most reactions were mild and well-tolerated. Of 14 patients who had severe reactions, temporary treatment interruption was necessary in 3 patients and a decreasing dose was required in another 3 patients. There were no statistically significant differences in type, severity, or number of cutaneous reactions between responders (29/58) and non-responders (29/58) to EGFR inhibitors. At median follow-up time of 11.92±1.08 months, no patient died from cutaneous toxicities. Nine patients died from cancer and 11 patients lost to follow-up. CONCLUSION: In this Asian population, almost all patients (96.7%) developed cutaneous toxicities of EGFR inhibitors. Xerosis, acne, and desquamation were common in Asian cancer patients. Most reactions were mild and well tolerated. Due to limited number of patients, this study did not show significant associations between cutaneous toxicities and tumor response.

Rash management and treatment persistence of cancer patients treated with epidermal growth factor receptor inhibitors in the Truven MarketScan® research database.

PURPOSE: Rash toxicity is a common, expected class effect of epidermal growth factor receptor (EGFR) inhibitors. Although rash management is practiced, it is not well characterized in the real-world setting. We describe the management of rash that developed while receiving EGFR-inhibitor therapy and how rash affects treatment duration, using Truven MarketScan® Research Database, a US medical claims database. METHODS: Adult patients who received EGFR-inhibitor treatment between 2004 and 2015 after a diagnosis of colon, head and neck, lung, breast, or thyroid cancer were identified. Descriptive analyses were conducted to describe occurrence of rash during the EGFR-inhibitor treatment period, EGFR-inhibitor treatment persistence and management of rash, including treatment and cost. RESULTS: Of 44,533 eligible patients, 4649 (10.4%) had records of rash during the EGFR-inhibitor treatment period, and of patients experiencing rash, 2891 (62.2%) received prescription drugs for rash treatment. Treatment persistence with an EGFR inhibitor was longer among patients experiencing rash compared with no rash (median 178 vs. 80 days for EGFR-TKIs, 85 vs. 57 days for EGFR-monoclonal antibodies), especially among patients with rash who were treated for rash (208 days for EGFR-tyrosine kinase inhibitors, 104 days for EGFR- monoclonal antibodies). Annualized cost during EGFR-inhibitor treatment was lowest among patients not experiencing rash (US$185,619), followed by rash patients receiving drugs for rash management (US$215,561), and highest among rash patients not treated for rash (US$267,105). CONCLUSION: Our findings suggest that management of EGFR inhibitor-associated rash could be important for EGFR-inhibitor treatment persistence.

Dermatologic Reactions to Targeted Therapy: A Focus on Epidermal Growth Factor Receptor Inhibitors and Nursing Care.

Cancer treatments usually have side effects of bone marrow depression, mucositis, hair loss, and gastrointestinal issues. Rarely do we think of skin side effects until patients have been treated successfully with epidermal growth factor receptor inhibitors (EGFRi). Those reactions include papulopustular rash, hair changes, radiation dermatitis enhancement, pruritus, mucositis, xerosis, fissures, and paronychia. This article discusses the common skin reactions seen when using EGFRi and presents an overview of skin as the largest and important organ of the body, including an overview of skin assessment, pathophysiology of the skin reactions, nursing care involved, and introduction to oncodermatology.

Nursing Management of Cutaneous Toxicities From Epidermal Growth Factor Receptor Inhibitors.

BACKGROUND: Personalized targeted therapies have become an emerging paradigm in cancer treatment. Although generally more tolerable than other chemotherapeutic agents, one therapy, epidermal growth factor receptor inhibitors (EGFRIs), commonly results in the formation of cutaneous toxicities, which can negatively affect patients' treatment adherence and quality of life. OBJECTIVES: The aim of this article is to review nursing management strategies for EGFRI-related cutaneous toxicities. METHODS: A systematic literature review was performed, including database searches in PubMed/MEDLINE®, CINAHL®, Cochrane Library, PsycINFO®, and Web of Science. FINDINGS: Nurses are essential to the management of EGFRI-related cutaneous toxicities and are in an ideal position to provide supportive care throughout the course of the EGFRI treatment. The aim of nursing management is to maintain patients' treatment adherence and quality of life by employing a preemptive and proactive approach. Patient education is the most frequently reported management strategy. However, treatment options and management strategies are largely anecdotal and based on individual reports and expert opinions. Although no evidence-based management strategies exist, nurses can rely on existing assessment tools and guidelines to provide patients with symptom management and supportive care.

Unique presentations of epidermal growth factor receptor inhibitor-induced papulopustular eruption related to bacterial superinfection.

Epidermal growth factor receptor (EGFR) inhibitors have been reported to induce numerous cutaneous side effects, the most notable of which is a papulopustular eruption on the face, scalp, and central chest. The typical presentation consists of inflamed papules, often with pustules, favoring a seborrheic distribution. The pustules of the EGFR inhibitor-induced papulopustular eruption are commonly sterile but bacterial superinfection is not uncommon. We report two unique presentations of the papulopustular eruption that were found to be associated with Staphylococcus aureus superinfection. One patient presented with an abrupt onset of nearly confluent red plaques on the cheeks, forehead, chin, and neck, with innumerable studded pinpoint pustules. The other patient had a long-standing untreated papulopustular eruption on the scalp, which resulted in widespread erythema, large thick plaques of serous crust, pustular exudate, and associated alopecia. Both patients quickly resolved with non-tetracycline oral antibiotics combined with topical steroid treatment.

[Clinical observation of EGFR-TKI as a first-line therapy on advanced non-small cell lung cancer].

BACKGROUND AND OBJECTIVE: It has been proven that epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) significantly benefits advanced non-small cell lung cancer (NSCLC) patients harboring EGFR mutations in progression-free survival time with better tolerance. This study is undertaken to analyze efficacy and tolerance of advanced NSCLC patients harboring EGFR mutations taking EGFR-TKI as a first-line therapy. METHODS: Tumor samples from 54 patients with advanced NSCLC were examined for EGFR activating mutations (deletion mutation in exon 19 and the L858R point mutation in exon 21) by direct sequencing. The patients were first-line treated with oral administration of EGFR-TKI until disease progression. The efficacy and adverse events were observed, and survival was followed up. RESULTS: Among the patients, 61% (33 of 54) had EGFR exon 19 deletion, and 39% (21 of 54) had EGFR L858R point mutation. All patients received first-line TKI therapy. The total response rate was 96%, median progression free survival (PFS) was 8.3 months and median survival was 19.5 months. The patients with EGFR exon 19 deletion had significantly longer median PFS (9 versus 7 months, P=0.002) and longer median overall survival (OS)(25 versus 16 months, P=0.001) than patients with EGFR L858R point mutation. There is no significance in efficacy between gefitinib and erlotinib, and gefitinib is safer than erlotinib. The most common adverse events were rash and diarrhea. Two (4%) grade 4 skin toxity effects, two (4%) grade 3 aminotransferase level elevations, and one (1) grade 3 stomatitis were observed. CONCLUSION: The first-line EGFR-TKI treatment in advanced NSCLC patients harboring EGFR mutations is efficient and safe, which is more efficient in patients with EGFR exon 19 deletion than those with EGFR L858R mutation.

Phase II study of gefitinib as a first-line therapy in elderly patients with pulmonary adenocarcinoma: West Japan Thoracic Oncology Group Study 0402.

OBJECTIVE: Elderly patients prefer to receive less-toxic therapy. Monotherapy using drugs such as vinorelbine, gemcitabine or docetaxel is a preferable chemotherapy in elderly patients with advanced non-small-cell lung cancer. Gefitinib shows remarkable efficacy in patients with advanced non-small-cell lung cancer, who have activating epidermal growth factor receptor mutations. Adenocarcinoma histology is related to these mutations. Therefore, we conducted a phase II study of gefitinib as a first-line therapy in elderly patients with pulmonary adenocarcinoma. METHODS: Eligible patients were 70 years or older, had pulmonary adenocarcinoma, stage IIIB or IV disease, an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ functions. Patients were treated with oral gefitinib 250 mg daily until disease progression or unacceptable toxicity. RESULTS: Thirty-one patients were enrolled, of whom 30 were eligible. The median age was 78.5 years. The response rate was 20%, the disease control rate was 47%, the median progression-free survival was 2.7 months and the median overall survival was 11.9 months. Narrowing it down to those who had never smoked, the response rate increased to 43%, the disease control rate increased to 57%, the median progression-free survival prolonged to 7.1 months and the median overall survival prolonged to 13.0 months. The most frequent toxicity was rash. Other major toxicities were diarrhea, anorexia, liver dysfunction and anemia. These toxicities were mild and easily managed. CONCLUSIONS: Gefitinib as a first-line therapy is active and well tolerated in elderly patients with pulmonary adenocarcinoma, especially in those who have never smoked.

Epidermal growth factor receptor (EGFR) inhibitor-induced rash: a consecutive patient series that illustrates the need for rigorous palliative trials.

PURPOSE: Rash is the most common side effect of epidermal growth factor receptor (EGFR) inhibitors and negatively impacts quality of life. This single-institution study sought to explore how rash is currently managed outside a clinical trial setting and to further characterize general clinical aspects of this rash. METHODS/RESULTS: Among 4101 consecutive patients with cancer of the lung, colorectum, pancreas, and head and neck, 138 had received an EGFR inhibitor. Within this group, 96 (69%) developed a rash. Forty-nine of these patients were prescribed rash therapy, and a total of 26 different palliative regimens were used. Surprisingly, most patients, with the exception of 2, appear to have manifested evidence of rash improvement-even when unproven or disproved therapies had been prescribed. Fourteen patients stopped their EGFR inhibitor because of rash, and 11 were then able to restart. No demographic variables were able to predict rash development. CONCLUSION: The observation that multiple, largely unproven, anecdotal therapies are being prescribed to palliate EGFR inhibitor-induced rashes underscores the need for more rigorous, prospective palliative trials.

[Erlotinib in the treatment of advanced non-small-cell lung cancer (NSCLC)].

OBJECTIVE: Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement of survival in non-small-cell lung cancer (NSCLC) after the failure of front-line chemotherapy. The aim of this study was to evaluate the antitumor efficacy and toxicity of Erlotinib in the treatment of advanced NSCLC patients. METHODS: A total of 104 patients with advanced NSCLC admitted in our department during December 2006 to November 2008 were enrolled in this study. Eligible patients received oral Erlotinib 150 mg/d until disease progression or intolerable toxicity. Best clinical response was determined using RECIST criteria, the adverse events were evaluated according to the NCI criteria. RESULTS: The total effective rate was 27.9% (29/104) and the clinical benefit was 76.0% (79/104). The median progression-free survival was 5.1 months (95%CI 4.0 - 8.0). The median survival time was 13.1 months (95%CI 10.0 - 15.7). The 1-year survival rate was 61.5%. Significant survival benefit from erlobinib therapy was observed for patients with good personal status (HR 0.56, P = 0.006), adenocarcinoma (HR 0.43, P = 0.004) and skin rash (HR 0.46, P = 0.005). But patients with smoking (HR 2.75, P < 0.001) and liver metastasis (HR 2.91, P = 0.002) add the risk of death. The adverse events were mild (grade < or = 2), most common toxicities were skin rash in 73.1% (76/104) and diarrhea in 41.3% (43/104). Only 6.7% (7/104) patients got adverse events of grade > or = 3. CONCLUSION: Erlotinib is an effective and well-tolerated treatment option for advanced NSCLC and could offer an alternative for patients after the failure of first-line chemotherapy, unsuitable for or not wishing to receive chemotherapy.