Search

Non-small cell lung cancer (NSCLC) with brain metastases (BM) is difficult to treat and associated with poor survival. This study assessed the impact of BM on healthcare-related utilization and costs (HRUC) among patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Adults newly-diagnosed with metastatic NSCLC, initiating first-/second-generation EGFR-TKI treatment, with BM or no BM (NBM), were identified retrospectively from IBM MarketScan healthcare claims databases (2013–2017). HRUC were measured during the variable-length follow-up period. Generalized linear models assessed the impact of BM on total healthcare costs, standardized to 2017 US$. Overall, 222 BM and 280 NBM patients were included, with a mean duration of follow-up of 14 months. Adjusted NSCLC-related and all-cause costs over average follow-up were 1.2 times higher among BM patients (Δ$5,640 and Δ$6,366, respectively; p <0.05); differences were driven primarily by radiation treatment and radiology. More than two times more BM than NBM patients received NSCLC-related radiation treatment, in both inpatient (15.3% vs 6.8%; p <0.05) and outpatient settings (87.8% vs 37.5%; p <0.05). Per-patient per-month (PPPM) radiation costs were also higher among BM patients, both inpatient ($796 vs $464, p =0.172) and outpatient ($2,443 vs $747, p <0.05). All-cause PPPM radiology visits (2.0 vs 1.3) and associated costs ($3,824 vs $1,621) were higher among BM patients (both p <0.05). NSCLC-related HRUC, especially those attributable to radiation treatment, were higher among patients with BM. Future research should compare the potential for CNS-active EGFR-TKIs vs first-/second-generation EGFR-TKIs combined with radiotherapy to reduce HRUC. [ABSTRACT FROM AUTHOR]

Background: Current clinical guidelines recommend epidermal growth factor receptor (EGFR) mutational testing in patients with metastatic non-small cell lung cancer (NSCLC) to predict the benefit of the tyrosine kinase inhibitor erlotinib as first-line treatment. Proteomic (VeriStrat) testing is recommended for patients with EGFR negative or unknown status when erlotinib is being considered. Departure from this clinical algorithm can increase costs and may result in worse outcomes. We examined EGFR and proteomic testing among patients with NSCLC within the Department of Veterans Affairs (VA). We explored adherence to guidelines and the impact of test results on treatment decisions and cost of care.Methods: Proteomic and EGFR test results from 2013 to 2015 were merged with VA electronic health records and pharmacy data. Chart reviews were conducted. Cases were categorized based on the appropriateness of testing and treatment.Results: Of the 69 patients with NSCLC who underwent proteomic testing, 33 (48%) were EGFR-negative and 36 (52%) did not have documented EGFR status. We analyzed 138 clinical decisions surrounding EGFR/proteomic testing and erlotinib treatment. Most decisions (105, or 76%) were concordant with clinical practice guidelines. However, for 24 (17%) decisions documentation of testing or justification of treatment was inadequate, and 9 (7%) decisions represented clear departures from guidelines.Conclusion: EGFR testing, the least expensive clinical intervention analyzed in this study, was significantly underutilized or undocumented. The records of more than half of the patients lacked information on EGFR status. Our analysis illustrated several clinical scenarios where the timing of proteomic testing and erlotinib diverged from the recommended algorithm, resulting in excessive costs of care with no documented improvements in health outcomes. [ABSTRACT FROM AUTHOR]

Background Cigarette smoke and asbestos are recognized causes of lung carcinoma and together promote carcinogenesis. Adenocarcinoma is currently the most common cause of lung cancer in the USA and it has been linked to both smoking and asbestos exposure. Mutations in the epidermal growth factor gene receptor (EGFR) occur predominantly in non-smokers with adenocarcinoma. Methods Mutations in the EGFR gene were investigated using next-generation sequencing. Results We report the presence of EGFR exon point mutations in the pulmonary adenocarcinomas of three never-smokers occupationally exposed to asbestos. Conclusion The role of asbestos as a possible cause of EGFR mutagenesis requires further investigation. Am. J. Ind. Med. 60:306-309, 2017. © 2017 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: Amivantamab was approved on May 21st, 2021, by United States food and drug administration with the brand name Rybervant, used particularly for adult patients with exon20 insertion of epithelial growth factor receptor with locally advanced metastatic non-small cell lung cancer., Objective: In this review, we explain the non-small cell lung cancer and molecular distinctions between non-small cell lung cancer and small cell lung cancer. We also conclude numerous components of non-small cell lung cancer, which include signs and symptoms of Amivantamab in inhibiting the cancer cell growth, various clinical trials on Amivantamab, adverse effects, and the contraindications of Amivantamab., Methods: A comprehensive literature search was conducted in the relevant databases like ScienceDirect, PubMed, ResearchGate, and Google Scholar to identify studies., Conclusion: Amivantamab is a new bispecific antibody that targets non-small cell lung cancer through two different pathways, i.e., by binding to epithelial growth factor receptor and mesenchymal epithelial transition factor. Amivantamab gets tightly bound to Fcγ3R, and thus, mediates the macrophage and NK-cell for the killing of cancer cells. Biological treatment of Amivantamab shows effectiveness against the epithelial growth factor receptor Exon20 insertions according to the preclinical data of the animal model., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Abstract: Introduction: The identification of somatic genomic aberrations in non-small-cell lung cancer (NSCLC) is part of evidence-based practice guidelines for care of patients with NSCLC. We sought to establish the frequency and correlates with these changes in routine patient–tumor sample pairs. Methods: Clinicopathologic data and tumor genotype were retrospectively compiled and analyzed from an overall cohort of 381 patient–tumor samples. Results: Of these patients, 75.9% self-reported White race, 13.1% Asian, 6.5% Black, 27.8% were never-smokers, 54.9% former-smokers and 17.3% current-smokers. The frequency of EGFR mutations was 23.9% (86/359), KRAS mutations 34.2% (71/207) and ALK FISH positivity 9.1% (23/252) in tumor samples, and almost all had mutually exclusive results for these oncogenes. In tumors from White, Black and Asian patients, the frequencies of EGFR mutations were 18.4%, 18.2% and 62%, respectively; of ALK FISH positivity 7.81%, 0% and 14.8%, respectively; and of KRAS mutations 41.6%, 20% and 0%. These patterns changed significant with increasing pack-year history of smoking. In White patients, the frequencies of EGFR mutations and ALK FISH positivity decreased with increasing pack-year cohorts; while the frequencies of KRAS mutations increased. Interestingly, in Asian patients the frequencies of EGFR mutations were similar in never smokers and in the cohorts with less than 45pack-year histories of smoking and only decreased in the 45pack-year plus cohort. Conclusions: The frequencies of somatic EGFR, KRAS, and ALK gene abnormalities using routine lung cancer tissue samples from our United States-based academic medical practice reflect the diverse ethnicity (with a higher frequency of EGFR mutations in Asian patients) and smoking patterns (with an inverse correlation between EGFR mutation and ALK rearrangement) of our tested population. These results may help other medical practices appreciate the expected results from introduction of routine tumor genotyping techniques into their day-to-day care of NSCLC. [Copyright &y& Elsevier]

Purpose: Elderly patients with esophageal cancer who are not candidates for chemoradiation may benefit from targeted agents; hence erlotinib combined with radiotherapy was evaluated in this trial. Materials and Methods: Patients >65 years with carcinoma of the thoracic esophagus or gastroesophageal junction who were not eligible for platinum-based treatment received erlotinib daily for 1 year starting on day 1 of radiotherapy [50.4 Gy days 1-28 (Mon-Fri) at 1.8 Gy per fraction]. Response was assessed by endoscopy and computed tomography. The primary endpoint was overall survival (OS), and secondary endpoints were complete response, progression-free survival (PFS) and toxicity. Results: The ECOG performance status in the 17 study patients was 0,1 and 2 in 2, 12 and 3 patients, respectively; 1, 5, 7 and 4 patients were in stage I, II, III and IV, respectively; adenocarcinoma was noted in 16 patients and squamous cell carcinoma in 1; there were 3 current, 12 past and 2 never smokers. Median OS was 7.3 months (95% confidence interval, CI: 3.8-22.3) with 14 deaths. There were 2 mucosal complete responses, 1 residual carcinoma in situ and 3 partial endoscopic responses in 9 patients who had endoscopy after radiotherapy. Estimated PFS was 4.5 months (95% CI: 2.4-7.3). Progression was distant (n = 3), locoregional (n = 6), unknown (n = 5) and too early (n = 3). Estimated 1-year survival was 29% (95% CI: 11-51%), 5 patients lived >12 months. Treatment-related toxicities of grade 3-4 occurred in 5 patients. Patients with epidermal growth factor receptor amplification and never smokers had the longest OS (22.3 and 16.6 months, respectively). Conclusions: Erlotinib with radiotherapy is tolerable and warrants further biomarker-driven evaluation in this population. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cetuximab and panitumumab, monoclonal antibodies used to target the epidermal growth factor receptor (EGFR), were recently approved by the United States Food and Drug Administration for use as single agents or in combination with other chemotherapy drugs in the treatment of metastatic colorectal cancer. The anti-EGFR monoclonal antibodies, either as single agents or in combination with chemotherapy, have demonstrated clinical activity in this setting. When combined with standard cytotoxic chemotherapy or other targeted agents (e.g., bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody), anti-EGFR monoclonal antibodies have been well tolerated and produced minimal toxicities. However, cetuximab and panitumumab appear to benefit only select patients. Predictive markers of efficacy, including EGFR overexpression, development of skin rash, and the absence of a K-ras mutation, have been evaluated in clinical studies to identify patients likely to respond to anti-EGFR monoclonal antibody therapy. This review discusses recent clinical studies of anti-EGFR monoclonal antibodies in the treatment of metastatic colorectal cancer, predictive markers of their efficacy, and common toxicities associated with their use. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, there are no reliable markers able to identify patients with nonsmall cell lung cancer (NSCLC) that will develop metastases to the brain. The authors investigated associations between immunohistochemical markers and the development of brain metastases in patients with NSCLC.Methods: This was a hospital-based, case-control study of patients who were newly diagnosed with NSCLC between 1989 and 2003, developed brain metastases, and had pathology material available from both the primary NSCLC and the brain metastases. These patients were compared with a control group of patients who had NSCLC and no evidence of brain metastases. NSCLC was examined for expression levels of Ki-67, caspase-3, vascular endothelial growth factor A (VEGF-A), VEGF-C, E-cadherin, and epidermal growth factor receptor (EGFR) in 54 surgical pathology specimens using immunohistochemistry, and associations were evaluated between those markers and the development of brain metastases.Results: Brain metastases developed after a median of 12.5 months (range, 1.7-89.4 months) after the diagnosis of NSCLC. A significantly increased risk of developing brain metastases was associated with patients with NSCLC who had primary tumors with high Ki-67 levels (adjusted odds ratio [OR] of 12.2; 95% confidence interval [95% CI], 2.4-70.4 [P < .001]), low caspase-3 expression (adjusted OR of 43; 95% CI, 5.3 to >100 [P < .001]), high VEGF-C expression (adjusted OR of 14.6; 95% CI, 2.0 to >100 [P < .001]), and low E-cadherin (adjusted OR of 3.6; 95% CI, 0.9-16.4 [P = .05]). No significant risk was associated with VEGF-A or EGFR expression. High Ki-67 expression also was associated with a shorter overall survival (P = .04).Conclusions: The results of the current study indicated that patients with NSCLC who had high Ki-67 expression, low caspase-3 expression, high VEGF-C expression, and low E-cadherin expression in their tumors may benefit from close surveillance because they may have an increased risk of developing brain metastases. [ABSTRACT FROM AUTHOR]

There has been intense investigation into the epidermal growth factor receptor (EGFR) as a therapeutic target in the treatment of non-small cell lung cancer (NSCLC). Currently there are two EGFR tyrosine kinase inhibitors, erlotinib and gefitinib, approved for the treatment of advanced NSCLC. In a phase III trial (BR.21), treatment with erlotinib resulted in a statistically significant improvement in overall survival in patients who had experienced progression after one or two previous chemotherapy treatments in comparison with best supportive care (BSC). In contrast, in the Iressa Survival Evaluation in Lung Cancer (ISEL) trial, treatment with gefitinib did not result in a statistically significant improvement in overall survival time in comparison with BSC in patients who had received one or two previous chemotherapy treatments and were refractory to or intolerant of the previous chemotherapy. After the results of the ISEL trial, the U.S. Food and Drug Administration restricted the use of gefitinib, and gefitinib was effectively removed from routine clinical practice within the U.S. However, gefitinib was approved in other countries and clinical trials investigating gefitinib continued. Recently the Iressa Nonsmall cell lung cancer Trial Evaluating REsponse and Survival against Taxotere (INTEREST) trial met the primary endpoint of demonstrating noninferiority in terms of overall survival for gefitinib (250 mg daily) in comparison with docetaxel (75 mg/m2 every 3 weeks). Patients treated with gefitinib experienced a lower rate of treatment-related toxicity and higher rate of improvement in quality of life. Results of recent gefitinib trials have been provocative, and suggest a role for gefitinib in the treatment of advanced NSCLC. [ABSTRACT FROM AUTHOR]

The combination of chemotherapy and targeted therapies is rapidly becoming the standard of care in the treatment of metastatic colorectal cancer. Panitumumab (formerly ABX-EGF) is a fully human antibody developed to target the human epidermal growth factor receptor (EGFR/HER-1), which is expressed in up to 75% of patients with colorectal cancer. As a fully human antibody, panitumumab can be administered without any premedication and few infusion reactions have been reported. It has recently been approved in the USA for the treatment of colorectal cancer as a single agent in the salvage setting. Ongoing studies are being performed to determine whether the addition of panitumumab to standard treatment for metastatic colorectal cancer will improve the survival of these patients. [ABSTRACT FROM AUTHOR]

Worldwide, approximately 1.3 billion individuals are current smokers, and smoking is the second major cause of death. Currently, lung cancer is the most common type of cancer in Europe, and the third in the U.S. Until now, cytotoxic chemotherapy has had a limited impact on survival in metastatic non-small cell lung cancer (NSCLC). The central role of epidermal growth factor (EGF) and its receptor (EGFR) in lung carcinogenesis is well recognized. Genetic polymorphisms are variants in individual genomes that may be responsible for different functional molecular roles and contribute to variability in drug pharmacokinetic and pharmacodynamic processes. Herein, we review the literature on EGF and EGFR functions and activities, particularly the current role of their functional polymorphisms as related to NSCLC. [ABSTRACT FROM AUTHOR]

Human cytomegalovirus (HCMV) is the leading cause of congenital viral infection in the United States and intrauterine transmission of HCMV occurs in approximately 40% of pregnant women with primary HCMV infection. Although HCMV infection during pregnancy clearly may be detrimental to fetal development, its consequences on placentation remain largely unexplored. In this study, the effects of HCMV infection on cytotrophoblast (CTB) invasion were investigated utilizing the first trimester extravillous CTB cell line SGHPL-4. HCMV infection significantly inhibited SGHPL-4 proliferation, epidermal growth factor (EGF)- and hepatocyte growth factor (HGF)-induced migration and invasion, as well as the secretion of matrix metalloproteinase (MMP)-2 and MMP-9. Both HCMV and EGF activated the EGF receptor (EGFR), inducing receptor tyrosine phosphorylation at specific residues. Of interest, EGFR was differentially activated by HCMV, and viral gene transcription was not required for the observed inhibitory effect on CTB invasiveness. These findings demonstrate that HCMV infection impairs CTB differentiation along the invasive pathway and that the differential regulation of EGFR by HCMV may contribute to impaired CTB function. Elucidating the mechanisms by which HCMV impairs placentation may be key in understanding fetal and maternal pathologies associated with intrauterine HCMV infection. [Copyright &y& Elsevier]

Background: Epidermal growth factor receptor and anaplastic lymphoma kinase play key roles in tumorigenesis and disease progression. Currently, targeted therapy is a better approach for cancer therapy compared with traditional chemotherapy. EGFR-based/ALK-based target therapies are key targets for drug development in cancer therapy., Objective: The objective of this study was to show a recent trend in research and development of EGFR-based/ALK-based targets and to better understand the Intellectual Property surrounding EGFR-based and ALK-based targets., Methods: EGFR-based and ALK-based targets were analyzed by comprehensive US patent analysis. US patents of EGFR-based/ALK-based targets were analyzed from September 2001 to September 2020., Results: The results indicated that the key technologies and methods of EGFR-based/ALK-based targets were developed by large global pharmaceutical companies or American companies/universities. Small molecular inhibitors showed a higher percentage in the number of patents of EGFRbased targets. In addition, the present study also showed recent small molecular targeted drugs approved by FDA., Conclusion: Global large pharmaceutical companies and American companies/universities have obvious advantages in the research and development of targeted drugs. EGFR-based target was still an attractive target for research and drug development in the past 10 years. Also, large global pharmaceutical companies prefer to complete key technology research and development by independent innovation instead of collaboration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: In EGFR mutation-positive NSCLC, dual EGFR/VEGFR inhibition compared to EGFR alone increases anti-tumor efficacy. The Phase III RELAY trial demonstrated superior PFS for ramucirumab plus erlotinib (RAM + ERL) over placebo plus erlotinib (PBO + ERL) (HR 0.591 [95% CI 0.461-0.760], p<0.0001). EGFR mutated NSCLC is less prevalent in Western versus Asian patients. This prespecified analysis evaluates efficacy and safety of RAM + ERL in EU and US patients enrolled in RELAY., Patients and Methods: Patients were randomized 1:1 to ERL + RAM (10 mg/kg IV) or PBO Q2W. Treatment continued until unacceptable toxicity or progressive disease. Patients were stratified by geographic region (East Asia vs "other" [EU/US and Canada (EU/US)]). Objectives included PFS, ORR, DoR, OS, PFS2, safety and biomarker analysis., Results: EU/US subset included 113/449 (25.9%) patients (58 RAM + ERL, 55 PBO + ERL). RAM + ERL improved PFS (20.6 vs 10.9 months, HR 0.605 [95% CI: 0.362-1.010]). ORR and DCR were similar, but median DoR was longer with RAM + ERL (18.0 vs 10.1 months, HR 0.527 [95% CI: 0.296-0.939]). OS and PFS2 were immature at data cut-off (censoring rates 81.0-81.8% and 67.3-79.3%, respectively). Most commonly reported Grade ≥3 TEAE for RAM + ERL was hypertension (17 [29.8%]) and for PBO + ERL, dermatitis acneiform (5 [9.1%])., Conclusion: EU/US subset analysis showed improved efficacy outcomes for RAM + ERL and a safety profile consistent with the overall population. Ramucirumab is a safe and effective addition to standard-of-care EGFR-TKI for EGFR mutation-positive metastatic NSCLC., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Targeted therapies, including tyrosine kinase inhibitors (TKIs) that target the sensitizing epidermal growth factor receptor (EGFR) gene are recommended for patients with non-small cell lung cancer (NSCLC). Most patients with NSCLC who test positive for the EGFR mutation and receive TKIs develop resistance to these drugs. Questions remain regarding which treatment sequence is optimal for patients with EGFR-mutant NSCLC, and few studies have evaluated patterns of TKI treatment use in NSCLC, irrespective of EGFR mutation status, in a real-world setting. This population-based study aimed to evaluate treatment patterns at a national level in the USA., Methods: This retrospective observational study used data from the US Oncology Network's iKnowMed database. Patients with advanced NSCLC who initiated first-line therapy with erlotinib and/or intravenous chemotherapy between January 1, 2012 and June 30, 2015 and met all other study criteria were included. Descriptive analyses assessed demographic and clinical characteristics and treatment patterns among the overall study cohort, as well as for specific erlotinib treatment subgroups, stratified by EGFR status., Results: Among the 3108 patients identified, 18.5% were EGFR positive, 49.8% were EGFR negative, and 31.7% were EGFR documented unknown. For the overall cohort, 18.4% received first-line erlotinib monotherapy, fewer than 1% received first-line combination therapy (erlotinib plus chemotherapy), 4.7% received second-line erlotinib monotherapy, and 3.3% received second-line combination therapy. First-line erlotinib monotherapy was used in 77.8% of all EGFR positive patients. Almost two-thirds of the overall cohort were not observed to have advanced to second-line therapy., Conclusions: As treatment options evolve, this study provides real-world treatment patterns that suggest concordance with NCCN guidelines and confirm the remaining need to understand sequencing of therapies and related outcomes., Funding: Eli Lilly and Company.

Transdifferentiation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) has been reported mostly in adenocarcinomas and has been described as a cause of acquired tyrosine kinase inhibitor (TKI) resistance. However, transdifferentiation has also been described in patients with different histologic characteristics and patients not exposed to TKIs and with no epidermal growth factor receptor (EGFR) mutation (the target of TKIs). To this date transdifferentiation remains poorly understood. We conducted a retrospective case series of patients who had biopsy-proven SCLC within 2 years after a diagnosis of NSCLC or in the same location as the known primary NSCLC. We found that 0.2% of lung cancer patients at our institution experienced transdifferentiation. Among these, 30 had adenocarcinoma and 16 had squamous cell carcinoma. In 27 of the 30 patients with adenocarcinoma (90%), SCLC was found in the same location as the known primary. In 14 of the 30 patients (47%), SCLC occurred within 2 years after the NSCLC diagnosis. In 12 of the 16 patients with squamous cell carcinoma (75%), SCLC was found in the same location as the known primary. In 8 of these 16 patients (50%), SCLC occurred within 2 years after the NSCLC diagnosis. Few patients with adenocarcinoma and none with squamous cell carcinoma were treated with TKIs or had an EGFR mutation. In conclusion the findings in the current study suggest that the discovery of SCLC histology after treatment of NSCLC may be more common than thought suggesting that further study is warranted to evaluate the phenomenon of transdifferentiation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: This is the first report of long-term (>10 years) safety, tolerability, and survival data on patients with non-small cell lung cancer (NSCLC) who received treatment with gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor., Methods: Patients with advanced NSCLC (N = 191) who entered the IRESSA Clinical Access Program (ICAP) (June 2011 to January 2013) and had previously obtained a clinical benefit from gefitinib therapy (including patients who had received gefitinib since 2001) were analyzed for adverse events (AEs). A subset of patients (n = 79) underwent retrospective chart review to capture demographic, safety, and survival data., Results: Seventy-five of 191 patients (39%) remained on long-term gefitinib therapy as of September 2016. Overall, serious AEs (SAEs) were reported in 64 patients (34%), the majority of which were attributed to underlying disease or comorbidities; only 3 patients (1.6%) had SAEs that were considered as possibly gefitinib-related. In the retrospective chart review cohort, 70% of patients were women; 58% were former smokers, and 30% were never-smokers; 56% were diagnosed with adenocarcinoma, and 13% were diagnosed with squamous carcinoma. Although EGFR mutational status was tested in only 17 patients (22%), it was assumed that most tumors were EGFR-mutation-positive. The median duration of gefitinib therapy was 11.1 years (7.8 years before and 3.5 years during ICAP), with 10-year and 15-year survival rates of 86% and 59%, respectively, from the initiation of therapy., Conclusions: A subset of long-term NSCLC survivors who were receiving gefitinib had an excellent long-term safety profile. Although it is assumed that most of these patients' tumors harbor EGFR mutations, molecular studies of available tumor specimens are planned to uncover the features that predict long-term survival. Cancer 2018;124:2407-14. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Reports the finding that mutations in the epidermal growth factor receptor (EGFR) gene improve the probability of beneficial outcome for the cancer drug, gefitinib. Details of the study by the Massachusetts General Hospital, which identified mutations in the tyrosine kinase domain of the EGFR; Suggestion of screening for EGFR mutations in lung cancer biopsies; Indication that the study was partially funded by the National Institutes of Health; Internet address where the research was published.