scholarly journals EGFR testing patterns and detection of EGFR exon 20 insertions among patients with NSCLC in the US

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S142-S143
Author(s):  
H M Lin ◽  
Y Yin ◽  
E Curran ◽  
V Crossland ◽  
Y Wu ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
The United States ◽  
Further Education ◽  
Smoking History ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Detection Rates ◽  
Asian Patients ◽  
Never Smokers ◽  
Exon 20

Abstract Introduction/Objective Epidermal growth factor receptor (EGFR) mutations are common in non-small cell lung cancer (NSCLC). EGFR exon 20 insertions (EGFRex20ins), a rare subset of EGFR mutations, are refractory to tyrosine kinase inhibitors. With the development of targeted therapies for EGFRex20ins, such as mobocertinib, molecular testing is required to optimize treatment. A better understanding of real-world EGFR detection patterns is needed to maximize patient outcomes. Methods/Case Report This retrospective study describes EGFR testing and EGFRex20ins detection patterns in patients with NSCLC in the United States. The Flatiron Health electronic health record database was used to identify patients ≥18 years, with advanced NSCLC, and with ≥2 clinic visits between 01/01/2011 and 12/31/2020. Baseline demographics, clinical characteristics, EGFR testing, and EGFRex20ins detection rates by sex, race, and smoking history were summarized. Results (if a Case Study enter NA) A total of 67,281 patients with NSCLC were identified. EGFR testing increased from 44% in 2011 to 77% in 2020. Of all patients, 44,926 (66.8%) were tested: 50.8% female; 3.3% Asian; 16.0% never-smokers. Of all patients, 22,355 (33.2%) were not tested: 41.4% female; 1.2% Asian; 7.5% never-smokers. Of those tested, 6,245 (13.9%) patients had EGFR mutations: 65.9% female; 11.8% Asian; 48.4% never-smokers. EGFRex20ins detection rates changed from 0.6% in 2011 to 1.0% in 2019 and 0.7% in 2020. Of those tested, 304 patients had EGFRex20ins: 58.2% female; 8.2% Asian; 50.3% never-smokers. EGFR testing was higher in females (71.2%) than males (62.8%), never-smokers (84.5%) than those with a smoking history (64.6%), and Asian patients (84.2%) than White (66.6%), Black (65.4%), or other patients (69.5%). Of those tested, EGFRex20ins mutations were detected in 0.8% of females (males: 0.6%), 2.2% of never-smokers (with smoking history: 0.4%), and 1.7% of Asians (White: 0.6%, Black: 0.6%, other patients: 0.7%) had EGFRex20ins. A similar trend was observed for EGFR mutations with higher proportions of females, never-smokers, and Asian patients affected. Conclusion EGFR testing and EGFRex20ins detection rates have increased. However, not all patient subgroups were tested at the same rate and undertesting occurred in all subgroups. Further education of specialists diagnosing NSCLC is warranted to ensure all patients receive biomarker testing and benefit from emerging EGFRex20ins- targeted therapies.

Smoking history and frequency of somatic KRAS mutations in adenocarcinoma of the lung

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7573-7573
Author(s):  
V. A. Miller ◽  
G. J. Riely ◽  
M. G. Kris ◽  
D. Rosenbaum ◽  
J. Marks ◽  
...  
Keyword(s):  
Cigarette Smoking ◽  
Mutational Analysis ◽  
Smoking History ◽  
Egfr Mutations ◽  
Molecular Testing ◽  
Kras Mutations ◽  
Exon 2 ◽  
Significant Difference ◽  
Never Smokers ◽  
Lung Adenocarcinomas

7573 Background: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are more common in patients with adenocarcinoma, especially those who smoked < 15 pack years (py). KRAS mutations are found in ∼25% of lung adenocarcinomas, most commonly in codons 12 and 13 of exon 2 (∼85%) and have been associated with poor prognosis in resected disease [Winton NEJM 2005] and resistance to EGFR tyrosine kinase inhibitors [Pao PLoS Med 2005]. KRAS mutations are uncommon in non-small cell lung cancer histologies other than adenocarcinoma. We sought to determine the association between quantitative measures of cigarette smoking and presence of KRAS mutations in lung adenocarcinomas. Methods: Standard direct sequencing techniques were used to identify KRAS codon 12 and 13 mutations in lung adenocarcinoma specimens from surgical resections between 2001 and 2006 and tumor specimens sent for KRAS molecular analysis in 2006. Surgical specimens were obtained from an institutional tumor bank. Detailed smoking history (age at first cigarette, packs per day, years smoked, years since quitting smoking) was obtained from the medical record and a patient-completed smoking questionnaire. Results: KRAS mutational analysis was performed on 408 lung adenocarcinomas from 242 women and 166 men. Median age was 68 (range 33–89). KRAS mutations were present in 19% (78/408, 95% CI 15 to 23%). The frequency of KRAS mutation was not associated with age or gender. The presence of KRAS mutations was not related to smoking history with 15% (9/61) of never smokers having KRAS mutations compared with 19% (51/275) of former smokers. When compared with never smokers, there was no significant difference in frequency of KRAS mutations for tumors from patients with 1–5 py (5%, p=0.44), 6- 10 py (12%, p=0.99), 11–15 py (25%, p=0.45), 16–25 py (16%, p=0.99), 26–50 py (25%, p=0.129), 51–75 py (20%, p=0.48), >75 py (20%, p=0.47) history of cigarette smoking. Conclusions: While the incidence of EGFR mutations has a strong inverse relationship with the amount of cigarettes smoked, allowing the selective molecular testing for EGFR mutations, the frequency of KRAS mutations cannot be predicted by age, gender, or smoking history. KRAS mutational analysis of all adenocarcinomas is required to reliably identify patients with KRAS mutations. No significant financial relationships to disclose.

Use of Cigarette-Smoking History to Estimate the Likelihood of Mutations in Epidermal Growth Factor Receptor Gene Exons 19 and 21 in Lung Adenocarcinomas

2006 ◽  
Vol 24 (11) ◽  
pp. 1700-1704 ◽  
Author(s):  
DuyKhanh Pham ◽  
Mark G. Kris ◽  
Gregory J. Riely ◽  
Inderpal S. Sarkaria ◽  
Tiffani McDonough ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
Smoking History ◽  
Egfr Mutations ◽  
Epidermal Growth ◽  
Former Smokers ◽  
Never Smokers ◽  
Lung Adenocarcinomas ◽  
Exon 19

Purpose Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers. Methods EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit ≥ 1 year ago), or current smokers (quit < 1 year ago). Results We detected EGFR mutations in 34 (51%) of 67 never smokers (95% CI, 38% to 64%), 29 (19%) of 151 former smokers (95% CI, 13% to 27%), and two (4%) of 47 current smokers (95% CI, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P < .001) or stopped smoking less than 25 years ago (P < .02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively). Conclusion The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.

Surrogate Predictive Biomarkers for Response to Anti-EGFR Agents: State of the Art and Challenges

2007 ◽  
Vol 22 (1_suppl4) ◽  
pp. 10-23 ◽  
Author(s):  
F. Cappuzzo ◽  
L. Toschi ◽  
G. Finocchiaro ◽  
C. Ligorio ◽  
A. Santoro
Keyword(s):  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Smoking History ◽  
Egfr Mutations ◽  
Gene Gain ◽  
Biological Variables ◽  
Drug Receptor ◽  
Exon 20

The epidermal growth factor receptor (EGFR) plays a key role in cancer development and progression in several human malignancies including non-small cell lung cancer (NSCLC). Several strategies aimed at inhibiting the EGFR have been investigated in the last years, including the use of small tyrosine kinase inhibitors (TKIs) directed against the intracellular domain of the receptor and monoclonal antibodies targeting its extracellular portion. Subgroups of patients who are more likely to respond to TKIs have been identified based on both clincal and biological features. Never-smoking history has emerged as the most relevant clinical characteristic predictive of response to TKIs in NSCLC, while presence of drug-sensitive EGFR mutations and EGFR gene gain represent critical biological variables associated with an improved outcome for patients exposed to these agents. Recent studies have highlighted the existence of biological factors involved in intrinsic and acquired resistance to TKIs, including k-ras, HER-2 and EGFR exon 20 mutations. Increasing knowledge of EGFR biology and drug-receptor interactions will allow to identify individuals who are likely to derive a clinical benefit from the proposed targeted therapy, sparing refractory patients expensive and potentially toxic treatment.

Targeted Therapies for Lung Cancer Patients With Oncogenic Driver Molecular Alterations

2022 ◽  
Author(s):  
Aaron C. Tan ◽  
Daniel S. W. Tan
Keyword(s):  
Lung Cancer ◽  
Targeted Therapies ◽  
Braf V600e ◽  
Standards Of Care ◽  
Molecular Testing ◽  
Precision Oncology ◽  
Early Stage Disease ◽  
Molecular Alterations ◽  
Oncogenic Driver ◽  
Exon 20

Lung cancer has traditionally been classified by histology. However, a greater understanding of disease biology and the identification of oncogenic driver alterations has dramatically altered the therapeutic landscape. Consequently, the new classification paradigm of non–small-cell lung cancer is further characterized by molecularly defined subsets actionable with targeted therapies and the treatment landscape is becoming increasingly complex. This review encompasses the current standards of care for targeted therapies in lung cancer with driver molecular alterations. Targeted therapies for EGFR exon 19 deletion and L858R mutations, and ALK and ROS1 rearrangements are well established. However, there is an expanding list of approved targeted therapies including for BRAF V600E, EGFR exon 20 insertion, and KRAS G12C mutations, MET exon 14 alterations, and NTRK and RET rearrangements. In addition, there are numerous other oncogenic drivers, such as HER2 exon 20 insertion mutations, for which there are emerging efficacy data for targeted therapies. The importance of diagnostic molecular testing, intracranial efficacy of novel therapies, the optimal sequencing of therapies, role for targeted therapies in early-stage disease, and future directions for precision oncology approaches to understand tumor evolution and therapeutic resistance are also discussed.

Smoking history and adherence to cancer-related recommendations in a primary care setting

2021 ◽  
Author(s):  
Roger J Zoorob ◽  
Maria C Mejia ◽  
Jennifer Matas ◽  
Haijun Wang ◽  
Jason L Salemi ◽  
...  
Keyword(s):  
Primary Care ◽  
Cancer Screening ◽  
Pap Smear ◽  
Task Force ◽  
Smoking Status ◽  
The United States ◽  
Smoking History ◽  
Former Smokers ◽  
Never Smokers ◽  
Primary Care Practices

Abstract Public health prevention efforts have led to overall reductions in mortality from screening-preventable cancers. We explored cancer screening behaviors of smokers, former smokers, and nonsmokers among patients of large primary care practices to discover the relationship between smoking status and previous adherence to the United States Preventive Services Task Force breast, cervical, and colorectal cancer screening recommendations. Our descriptive study of electronic medical record data included 6,029 established primary care patients. Multi-predictor log-binomial regression models yielded prevalence ratios (PRs) and 95% confidence intervals (CIs) to determine associations between smoking status and the likelihood of nonadherence. All models were adjusted for race/ethnicity, age, insurance, primary care specialty, number of comorbidities, and sex. Smoking history was obtained from all participants in January 2020. Current smokers accounted for 4.8%, while 22.7% were former smokers, and 72.5% were never smokers. Current smokers (compared to never smokers) were 63% more likely to be mammogram nonadherent (PR: 1.63, 95% CI: 1.31 to 2.02), 26% more likely to be Pap smear nonadherent (PR: 1.26, 95% CI: 1.04 to 1.53), and 39% more likely to be colonoscopy nonadherent (PR: 1.39, 95% CI: 1.16 to 1.66). Current smokers and former Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation smokers had on average 2.9 comorbidities while never smokers had on average 2.1 comorbidities. Our findings showed that current smokers experienced significantly lower rates of cancer screening compared to never smokers. Further research is needed to investigate and identify best practices for increasing cancer screening uptake in this population.

Frequency and clinical correlations of epidermal growth factor receptor (EGFR) mutations in a large cohort of Italian non-small cell lung cancer (NSCLC) patients (pts) within the EGFR FASTnet program.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18021-e18021
Author(s):  
Nicola Normanno ◽  
Carmine Pinto ◽  
Gian Luigi Taddei ◽  
Giancarlo Troncone ◽  
Paolo Graziano ◽  
...  
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
Sanger Sequencing ◽  
Advanced Nsclc ◽  
Mutational Analysis ◽  
Growth Factor Receptor ◽  
Smoking History ◽  
Egfr Mutations ◽  
Medical Oncologists ◽  
Exon 20

e18021 Background: Gefitinib was approved in Italy for treatment of pts with advanced NSCLC carrying mutant EGFR in May 2010. Methods: The EGFR FASTnet program was designed to facilitate the exchange of biological material, clinico-pathological data and reports between medical oncologists, primary pathologists and referral laboratories. EGFR mutational analysis was carried by Sanger sequencing, Real Time PCR, Pyrosequencing, Fragment Analysis and High resolution melting. The Italian Association of Medical Oncology (AIOM) and the Italian Society of Surgical Pathology and Cytopathology (SIAPEC-IAP) have full access to the anonymous EGFR FASTnet database. Results: As of December 31, 2011, 503 oncologists, 135 pathologists and 38 referral laboratories joined the EGFR FASTnet program. The enrolled cohort of 3819 pts with advanced NSCLC was significantly enriched for adenocarcinoma histology (3172 [83%]), female sex (1361 [36%]) and smoking history (never smoker 911 [24%], former smoker>15 yrs 880 [23%], light smoker 194 [5%]). Mutational analysis was feasible in 3567 pts (93%). At registration, 72% of the pts had not received yet treatment for advanced disease. Mutational analysis was carried by Sanger sequencing in 2021 cases (57%), Real Time PCR in 174 (5%), Pyrosequencing in 636 (18%) and other techniques in 736 (21%). EGFR mutations were found in 520 cases (14.6%): 334 in exon 19 (9.4%), 163 in exon 21 (4.6%), 7 in exon 18 (0.2%) and 16 in exon 20 (0.4%). Proportion of mutated cases was slightly higher with Real time PCR compared to other techniques: Sanger 14.8%, Real time PCR 21.3%, Pyrosequencing 13.5%, other 13.3% (p = 0.049). A higher mutation rate was found in never smokers (32.0%), light smokers (18.7%) and former smokers >15 yrs (12.4%), as well as in adenocarcinoma (15.7%) and females (25.2%). Conclusions: The pts for EGFR mutational screening are spontaneously selected by medical oncologists according to known predictive factors. The results of the mutational analysis from clinical practice in Italy are consistent with data from literature.

The CAP-IASLC-AMP molecular testing guideline for the selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11085-11085
Author(s):  
Marc Ladanyi ◽  
Phil T. Cagle ◽  
Mary Beth Beasley ◽  
Dhananjay Chitale ◽  
Sanja Dacic ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Randomized Clinical Trials ◽  
Kinase Inhibitors ◽  
Conflicts Of Interest ◽  
International Association ◽  
Smoking History ◽  
Egfr Mutations ◽  
Advisory Panel ◽  
Molecular Testing ◽  
Evidence Based

11085 Background: The College of American Pathologists (CAP), the International Association for the Study of Lung Cancer (IASLC), and the Association for Molecular Pathology (AMP) jointly initiated an effort to establish evidence-based recommendations for the molecular analysis of lung cancers required to guide EGFR- and ALK-directed therapies, addressing which patients and samples should be tested, and when and how testing should be performed. Methods: Three co-chairs without relevant conflicts of interest were selected, one from each of the sponsoring societies: CAP (P.T.C.), IASLC (M.L.), and AMP (N.I.L.). Writing and advisory panels were formed from additional experts from these societies. Unbiased literature searches were performed to capture articles up to February 2012, yielding 1,533 articles whose abstracts were screened to identify 521 pertinent articles that were then reviewed in detail for relevance. Evidence was formally graded for each of the recommendations first formulated by the co-chairs and panel members at a public meeting. Each guideline section was assigned to at least two panelists. Successive drafts were circulated for comments to the writing panel, the advisory panel, the public (online posting), and the three professional societies. Results: We generated 37 guideline items addressing 14 areas of EGFR and ALK testing. The major, evidence-based recommendations are to test for EGFR mutations and ALK fusions in all patients with advanced stage adenocarcinoma, regardless of sex, race, or smoking history, and to prioritize EGFR and ALK testing over other molecular predictive tests. Recommendations and expert consensus opinions were generated for all other key aspects of EGFR and ALK testing in lung cancer related to oncology and pathology practice and technical issues in molecular testing. Conclusions: As scientific discoveries and clinical practice outpace the completion of randomized clinical trials, evidence-based guidelines developed by expert practitioners are vital for communicating emerging clinical standards and thereby improving patient outcomes.

Phase II study of erlotinib in chemo-naive women with advanced pulmonary adenocarcinoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7591-7591 ◽  
Author(s):  
D. Jackman ◽  
N. I. Lindeman ◽  
J. Lucca ◽  
L. K. Morse ◽  
M. S. Rabin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
Smoking Status ◽  
Direct Sequencing ◽  
Progression Free Survival ◽  
Smoking History ◽  
Egfr Mutations ◽  
Kras Mutations ◽  
Grade 3 ◽  
Exon 20

7591 Background: Erlotinib is associated with a survival benefit over placebo for pts with advanced NSCLC who had received 1–2 prior regimens. Its role as initial therapy in clinically defined subgroups or in pts prospectively tested for EGFR mutations is less clear. Methods: Chemotherapy-naive women with adenocarcinoma, stage IIIB/IV, PS 0–1, who had formerly or never smoked, were enrolled and treated with erlotinib 150 mg PO daily, until the time of disease progression or unacceptable toxicity. Response rate was the primary endpoint. Secondary endpoints included overall survival, progression-free survival and toxicity. Tumor tissue adequate for genomic analysis was mandated and prospectively collected for determination of EGFR and KRAS mutations by direct sequencing. Results: From 11/04 to 10/06, 40 women were treated. Demographics: median age 65 yrs (range 36–87); 38 white, 1 black, 1 Asian; 30% PS 0, 70% PS 1; 20% BAC or adenoCA w/ predominant BAC features, 80% adenoCA w/o BAC features; smoking status: 63% former, 37% never. Toxicity: Rash (95%; 30% grade 3) and diarrhea (73%; 10% grade 3) were the most common toxicities. 50% of pts developed toxicity of grade 3 or greater. 5 pts were discontinued due to toxicity, with 2 deaths that were possibly treatment-related: 1 DIC, 1 hepatic failure. There were also two pts with PE (one fatal). Response: CR 0, PR 12 (30%), SD 11 (28%), and PD 10 (25%), 7 not evaluable. To date, 27 patients have progressed, with 14 deaths. Median PFS was 5.6 months; median overall survival has not yet been reached and exceeds 23 months. Of 32 patients sequenced for EGFR to date, there were 9 exon 19 deletions, 3 L858R mutations, and 1 exon 20 insertion. For the 12 pts prospectively determined to have classic EGFR mutations, RR was 75% (9 PR, 2 SD, 1 not evaluable). Of 15 pts w/ wild-type EGFR, only 1 response (7%) was achieved. The pt w/ the exon 20 insertion developed PD. Of 28 pts evaluated to date for KRAS, 6 KRAS mutations were found, w/ no responses in this group (2 PD, 4 SD). Conclusions: Preliminary results suggest that first-line erlotinib monotherapy may be a useful treatment strategy for women with adenocarcinoma and a limited smoking history. Response rate is particularly impressive for those subjects prospectively found to have an EGFR mutation, and poor for those with KRAS mutations. No significant financial relationships to disclose.

Comparison of the KRAS/EGFR mutation profile and survival of “collegiate smokers” and never smokers with advanced lung cancers.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7580-7580
Author(s):  
Anna M. Varghese ◽  
Camelia S. Sima ◽  
Jamie E. Chaft ◽  
Melissa Lynne Johnson ◽  
Yelena Yuriy Janjigian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Biology ◽  
Egfr Mutation ◽  
Stage Iiib ◽  
Smoking History ◽  
Egfr Mutations ◽  
Lung Cancers ◽  
Mutation Profile ◽  
Former Smokers ◽  
Never Smokers

7580 Background: In practice, we encounter patients (pts) with lung cancers who state they smoked only while in college. The impact of this degree of tobacco use on cancer biology is unknown. We have shown that EGFR mutations are less common in pts who smoked > 15 pack years (PY). We hypothesize that among pts with lung cancer the KRAS / EGFR mutation profile and overall survival (OS) of “collegiate smokers” (former smokers who smoked between 101 lifetime cigarettes and 5 PY) will be distinct from never smokers and former smokers with ≥ 15 PY. Methods: We collected age, sex, stage, and survival for pts evaluated from 2004 - 2009 with stage IIIB/IV lung cancer with known KRAS and EGFR status. ALK testing was not available routinely during this time. Smoking history was obtained using a patient completed survey. The Fisher exact test was used to compare mutation profiles. The log rank test was used to compare OS. Results: Smoking history and clinical data were available for 852 pts with Stage IIIB/IV lung cancer with known KRAS and EGFR status: 307 never smokers, 178 current smokers, and 367 former smokers. Of the former smokers, 55 were “collegiate smokers”, 61 had smoked 5-15 PY, and 251 had smoked ≥ 15 PY. The KRAS / EGFR mutation profiles by smoking history are shown below (Table). The KRAS / EGFR mutation profile of “collegiate smokers” is distinct from those of pts who were never smokers (p < .001) and former smokers with ≥ 15 PY (p < .001) but similar to that of pts who were former smokers with 5-15 PY (p = 0.9). Median OS after diagnosis of stage IIIB/IV lung cancer for “collegiate smokers” was 25 months (mos), compared to 32 mos for never smokers (p = 0.4) and 21 mos for former smokers with ≥ 15 PY (p = 0.63). Conclusions: “Collegiate smokers” are a distinct group of pts with a higher incidence of KRAS mutations and lower incidence of EGFR mutations compared to never smokers. These data suggest that even a small amount of cigarette smoking influences the biology of lung cancer. These findings reinforce the importance of doing mutation testing routinely for all pts with lung cancer to guide clinical care. [Table: see text]

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