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.

Clinical features of patients with lung adenocarcinomas harboring BRAF V600E mutations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8101-8101 ◽  
Author(s):  
Tongtong An ◽  
Jie Wang ◽  
Hua Bai ◽  
Zhijie Wang ◽  
Jun Zhao ◽  
...  
Keyword(s):  
Survival Rates ◽  
Multivariate Logistic Regression Analysis ◽  
Braf V600e ◽  
Chinese Patients ◽  
Smoking History ◽  
Egfr Mutations ◽  
Occurrence Rate ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Lung Adenocarcinomas

8101 Background: To investigate the prevalence, distribution, and prognostic role of activating BRAF mutations in Chinese patients with lung adenocarcinomas (ADCs). Methods: This retrospective study included 192 lung ADCs (97 males 50.5%, 95 females 49.5%). BRAF gene mutations were screened using AmoyDx BRAF V600E mutations detection kit. Mutations of EGFR and KRAS gene were also analyzed. Results: BRAF mutations were present in 8(4.17%) lung ADCs patients. V600E mutations were significantly more prevalent in females (6 of 96; 6.25%) than in males (2 of 97; 2.06%), as indicated by multivariate logistic regression analysis. Other clinocopathologic parameters, including age, smoking history, and tumor stage, were not significantly associated with V600E BRAF mutations. V600E-mutated tumors were not associated with different progression-free and overall survival rates comparing with non V600E-mutated tumors in this study. The frequency of EGFR and KRAS mutations in all patients were 42.7%(82/192) and 8.3%(16/192), respectivelyBRAF and EGFR were concomitantly mutated in three tumors. All tumors with BRAF mutations were found to be negative for KRAS mutations. Conclusions: We report for the first time to our knowledge that V600E BRAF mutation has high concomitant occurrence rate with EGFR mutations in Chinese lung ADCs patients. BRAF mutations were found to be independently associated only with female gender.

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.

Influence of moderate cigarette-smoking on the peri-implant clinicoradiographic inflammatory parameters around cement- and screw-retained dental implants

2020 ◽  
Author(s):  
Mana Alqahtani
Keyword(s):  
Cigarette Smoking ◽  
Dental Implants ◽  
Smoking History ◽  
Inflammatory Parameters ◽  
Significant Difference ◽  
Implant Retention ◽  
Level Of Significance ◽  
Soft Tissue Inflammation ◽  
Post Hoc ◽  
Adjustment Test

The aim was to assess the influence of moderate cigarette-smoking on the clinical (bleeding on probing [BoP] and probing depth [PD]) and radiographic (crestal bone resorption [CBR]) around cement- and screw-retained dental implants at 5 years’ follow-up. A questionnaire was used to collect information about age, gender, smoking history, duration of implants in function, jaw location of the implant, and daily toothbrushing and flossing. Peri-implant BoP, PD and CBR were measured in all groups. Group comparisons were performed using one-way analysis of variance and for multiple comparisons, the Bonferroni Post hoc adjustment test was performed. Level of significance was set at P&lt;0.05. Forty-eight patients (25 smokers and 23 non-smokers) had cement-retained dental implants; and 48 (24 smokers and 24 non-smokers) had screw-retained dental implants. Among patients with cement and screw-retained dental implants, PD (P&lt;0.05) and CBR (P&lt;0.05) were significantly higher among smokers than non-smokers. The peri-implant sites that demonstrated BoP were statistically significantly higher among non-smokers (P&lt;0.05) than smokers among patients with cement- and screw-retained dental implants. There was no statistically significant difference in peri-implant PD and CBR among smokers with cement- and screw-retained dental implants. Among non-smokers with cement and screw-retained dental implants, there was no statistically significant difference in BoP, PD and CBR. Cigarette-smoking is associated with an increased PD and CBR around cement- and screw-retained dental implants. Cigarette-smoking increases peri-implant soft tissue inflammation as well as loss of crestal bone and this relationship is independent of the type of implant retention protocol used.The author recommends that cement- and screw-retained dental implants are suitable for prosthesis restoration in non-smokers. Further studies on dual-smokers (individuals smoking cigarettes and other forms of tobacco products) are needed related to the clinicoradiographic inflammatory parameters around cement- and screw-retained dental implants

scholarly journals Lung Adenocarcinoma From East Asian Never-Smokers Is a Disease Largely Defined by Targetable Oncogenic Mutant Kinases

2010 ◽  
Vol 28 (30) ◽  
pp. 4616-4620 ◽  
Author(s):  
Yihua Sun ◽  
Yan Ren ◽  
Zhaoyuan Fang ◽  
Chenguang Li ◽  
Rong Fang ◽  
...  
Keyword(s):  
East Asian ◽  
Egfr Mutations ◽  
Driver Mutations ◽  
Single Institution ◽  
Pik3ca Mutations ◽  
Oncogenic Mutations ◽  
Oncogenic Driver ◽  
Never Smokers ◽  
Lung Adenocarcinomas ◽  
Concurrent Analysis

Purpose To determine the proportion of lung adenocarcinomas from East Asian never-smokers who harbor known oncogenic driver mutations. Patients and Methods In this surgical series, 52 resected lung adenocarcinomas from never-smokers (< 100 cigarettes in a lifetime) at a single institution (Fudan University, Shanghai, China) were analyzed concurrently for mutations in EGFR, KRAS, NRAS, HRAS, HER2, BRAF, ALK, PIK3CA, TP53 and LKB1. Results Forty-one tumors harbored EGFR mutations, three harbored EML4-ALK fusions, two harbored HER2 insertions, and one harbored a KRAS mutation. All mutations were mutually exclusive. Thus, 90% (47 of 52; 95% CI, 0.7896 to 0.9625) of lung adenocarcinomas from never-smokers were found to harbor well-known oncogenic mutations in just four genes. No BRAF, NRAS, HRAS, or LKB1 mutations were detected, while 15 had TP53 mutations. Four tumors contained PIK3CA mutations, always together with EGFR mutations. Conclusion To our knowledge, this study represents the first comprehensive and concurrent analysis of major recurrent oncogenic mutations found in a large cohort of lung adenocarcinomas from East Asian never-smokers. Since drugs are now available that target mutant EGFR, HER2, and ALK, respectively, this result indicates that prospective mutation testing in these patients should successfully assign a targeted therapy in the majority of cases.

scholarly journals Comparative Characteristics of Napsin A, TTF 1 and EGFR Mutation Expression in Mucinous Lung Cell Carcinomas

Folia Medica ◽  
2017 ◽  
Vol 59 (2) ◽  
pp. 174-182
Author(s):  
Sylvia N. Genova ◽  
Veselin T. Belovezhdov ◽  
Stoyan N. Bichev ◽  
Vladimir H. Danev
Keyword(s):  
Salivary Gland ◽  
Mutation Frequency ◽  
Egfr Mutation ◽  
Egfr Mutations ◽  
Common Pattern ◽  
Specificity And Sensitivity ◽  
Napsin A ◽  
Significant Difference ◽  
Pcr Technology ◽  
Lung Adenocarcinomas

AbstractBackground:Invasive mucinous lung adenocarcinomas are rare and account for 2%–10% of all lung adenocarcinoma cases. It is believed that Napsin A exhibits a weaker expression in mucinous adenocarcinomas compared with TTF1, but such correlation is still poorly researched.Aim:The aim of the study was to determine the frequency of mucinous to nonmucinous adenocarcinomas and compare specificity and sensitivity of monoclonal Napsin A with TTF1 in mucinous adenocarcinomas and define the frequency of EGFR mutations.Materials and methods:Eighty-four resected lung carcinomas were prospectively evaluated. All biopsies were analysed with p63, TTF1, monoclonal Napsin A, CK7, CK20 and CDX2 and were studied with real-time PCR technology.Results:In resected material we detected 49/84 (58.3%) adenocarcinomas and selected 21 mucinous adenocarcinomas out of 46 non-mucinous adenocarcinomas (45.6%). The most common pattern of mucinous adenocarcinomas is papillary - 24% and colloidal - 24%, followed by acinar - 19.2% and lepidic - 19.2%. mNapsin A was positive in 18/21 (85.7%) mucinous adenocarcinomas v/s 17/21 TTF1 positive (80.9%). EGFR mutations were detected in 3/21 cases with mucinous adenocarcinomas (14.3%): mucinous papillary, mucinous acinar and “salivary gland-like”.Conclusion:Our study demonstrates a high proportion of primary mucinous lung adenocarcinomas to primary non-mucinous adenocarcinomas. Sensitivity and specificity of mNapsin A and TTF1 did not show significant difference in pulmonary mucinous and non-mucinous adenocarcinomas, as mNapsin A gave greater sensitivity to mucinous adenocarcinomas. Our results indicate the same mutation frequency of EGFR in mucinous adenocarcinomas as mutation frequency detected in non-mucinous adenocarcinomas in the Bulgarian region.

scholarly journals Clinical Features and Surgical Treatment of Synchronous Multiple Primary Lung Adenocarcinomas With Different EGFR Mutations

2022 ◽  
Vol 11 ◽  
Author(s):  
Rirong Qu ◽  
Fan Ye ◽  
Dehao Tu ◽  
Yixin Cai ◽  
Xiangning Fu
Keyword(s):  
Clinical Features ◽  
Mutation Rate ◽  
Surgical Outcomes ◽  
Clinical Characteristics ◽  
Egfr Mutations ◽  
Driver Gene ◽  
Invasive Adenocarcinoma ◽  
Significant Difference ◽  
Multiple Primary ◽  
Lung Adenocarcinomas

BackgroundWith the popularity of lung cancer screening and advances in imaging technology, more and more synchronous multiple primary lung adenocarcinomas (SMPLA) are being diagnosed clinically, however, the clinical characteristics and prognosis of SMPLA with different EGFR mutations remains unclear. We aimed to explore clinical features and surgical outcomes of these patients to aid in the diagnosis and treatment of SMPLA.MethodsMedical records of patients with different EGFR mutations who have been diagnosed as SMPLA and underwent surgical resection from March 2015 to December 2019 were retrospectively analyzed. Clinical characteristics, surgical outcomes, recurrence-free survival (RFS) and overall survival (OS) were investigated.ResultsA total of 70 patients (68.6% female and 77.1% non-somkers) were included. Total of 161 lesions in all patients, 84.4% were ground-glass opacity (GGO) lesions. EGFR mutations were detected in 108 lesions, most of which were L858R (35.4%) and 19Del (20.5%). The mutation rate of mixed GGO is significantly higher than that of pure GGO and solid nodules (SN); the mutation rate of invasive adenocarcinoma is significantly higher than that of other histology subtypes; the mutation rate of lesions &gt;20 mm was significantly higher than that of ≤20 mm. However, there is no significant difference in the mutation rate of specific driver gene between different radiological features, pathological characteristics and sizes. After a median follow-up time of 29 months, the 3-year OS and RFS were 94.4% and 86.0%, respectively.ConclusionsA high discordance of EGFR mutations were identified between tumors in patients with SMPLA. Synchronous multiple lung adenocarcinomas with predominantly multiple GGO should be considered as SMPLA, and surgery may be aggressively performed for these patients due to a good prognosis.

scholarly journals Ανίχνευση μεταλλάξεων του EGFR και KRAS σε ασθενείς με μη-μικροκυτταρικό καρκίνο του πνεύμονα και διερεύνηση της αξίας τους ως προβλεπτικών παραγόντων ανταπόκρισης στη θεραπεία

2013 ◽  
Author(s):  
Αριστέα Καλυκάκη
Keyword(s):  
Kras Mutation ◽  
Smoking History ◽  
Egfr Mutations ◽  
Front Line ◽  
Kras Mutations ◽  
Primary Tumors ◽  
Mutation Status ◽  
Kras Mutation Status ◽  
Line Chemotherapy ◽  
Exon 19

The purpose of this study was to investigate whether the EGFR and KRASmutation status are predictive factors for Greeks patients with NSCLC. Initially, wecalculated the rate and the pattern of EGFR and KRAS mutations in 639 patients withNSCLC and then we correlated the mutations status with clinicopathologicalcharacteristics, the response to 1st line chemotherapy and patients’ overall survival.We also investigated the association of EGFR mutations with the EGFR geneamplification. Finally, in a group of 25 patients the mutation status of these genes inthe primary tumors and the corresponding metastasis was evaluated.The genetic analysis performed in FFPE tissue samples of primary tumor ormetastasis. DNA was extracted using universal techniques. For mutation analysis exons18, 19, 20 and 21 of the EGFR and exon 2 of KRAS genes were sequentially amplified bypolymerase chain reaction (PCR) and subjected to direct sequencing. Finally, EGFRamplification was determined by quantitative real time PCR.Analysis of EGFR mutations was successful performed in 634 patients andmutations were detected in 100 (15.8%) of them. Activating mutations were detected in 8.4%. The most common mutations were deletions of 4-5 codons in exon 19 (del 19,71.7%, 38/53) and the missense mutation at position 858 (L858R) in exon 21 (22.6%,12/53). Also in 47 (7.4%) patients other mutations were detected in four exons ofEGFR, which have been reported previously or are new. We found that the incidenceof EGFR mutations was statistically significant in women with no smoking history andwith adenocarcinoma histology.The mutation analysis of the KRAS gene was successfully performed on 399patients and mutations detected in 20.8% of them (83/399). Especially, 92.8% of themutations were found at codon 12 and 7.2% at codon 13. KRAS mutations weresignificantly associated with smoking history with higher incidence in smokers thannonsmokers. There was also a significant association between KRAS mutations andadenocarcinoma histology.The predictive value of EGFR and KRAS mutations was examined in a subgroupof patients (n=162) with NSCLC who received chemotherapy as 1st line therapy.Patients with classical EGFR mutations had a higher probability of response (55.6%) to front-line chemotherapy as compared to those with wild type EGFR (21.8%) (p =0.023). Multivariate analysis revealed the 'classical' activating EGFR mutations as anindependent predictive factor for response to 1st line chemotherapy. There was nosignificant correlation between the EGFR or KRAS mutation status and the time totumor progression. The presence of activating EGFR but not of KRAS mutations wasassociated with a significantly higher overall survival compared to patients withoutmutations treated with platinum-based front-line chemotherapy.Epidermal growth factor receptor and KRAS mutation status was differentbetween primary tumors and corresponding metastases in 7 (28%) and 6 (24%) of the25 patients, respectively. This discrepancy was not statistically significant with theMcNemar’s test.EGFR amplification was found in 7.2% (6/83) of primary tumors. Among thepatients with EGFR gene amplification none carried KRAS mutations while 2 had EGFR exon 19 deletion.

scholarly journals Cross-sectional study of smoking exposure: no differential effect on OCT metrics in a cohort of MS patients

2019 ◽  
Vol 5 (1) ◽  
pp. 205521731982840 ◽  
Author(s):  
Mattia Rosso ◽  
Dorlan J Kimbrough ◽  
Cindy T Gonzalez ◽  
Bonnie I Glanz ◽  
Brian C Healy ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Cross Sectional Study ◽  
Smoking History ◽  
Retinal Layer ◽  
Fiber Layer ◽  
Cross Sectional ◽  
Macular Volume ◽  
Smoking Exposure ◽  
Significant Difference ◽  
Never Smokers

Background Optical coherence tomography (OCT) provides quantitative measures of retinal layer thickness. Cigarette smoking is a risk factor for multiple sclerosis (MS) onset and disease severity: its effects on OCT metrics have not been assessed. Objective The objective of this study was to assess the effect of smoking history on retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform (GCIP) of MS patients by OCT. Methods 112 MS patients were recruited from the Brigham and Women’s Hospital. Spectralis OCT scans were acquired to measure GCIP, peripapillary RNFL, and total macular volume. Multivariable linear mixed effects regression model assessed RNFL and GCIP change with fixed effects for smoking history while adjusting for optic neuritis eye status, age, disease duration, sex, baseline EDSS, and disease modifying therapies (DMTs). Results Smoking histories were available for 102 patients: 46 (45.10%) had a history of smoking cigarettes and 56 (54.90%) never smoked. No statistically significant differences were found between ever-smokers and never-smokers with respect to GCIP, RNFL, and macular volume. Conclusion Our study shows no significant difference in retinal thickness between ever-smokers and never-smokers. If confirmed, this result suggests mechanistic differences between the retina and other central nervous system (CNS) compartments in response to smoking and should be noted when considering OCT as a surrogate measure of CNS activity.

Clinical characteristics of KRAS mutations in NSCLC and their impact on outcomes to first-line chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7588-7588
Author(s):  
Mohit Butaney ◽  
Jennifer Porter ◽  
Neal Ian Lindeman ◽  
Pasi A. Janne ◽  
Michael S. Rabin ◽  
...  
Keyword(s):  
Smoking Status ◽  
Egfr Mutations ◽  
Limited Information ◽  
Wild Type ◽  
First Line ◽  
Kras Mutations ◽  
Response To Chemotherapy ◽  
Significant Difference ◽  
The Impact ◽  
Line Chemotherapy

7588 Background: KRAS is one of the most commonly mutated oncogenes in non-small cell lung cancer (NSCLC). While the impact of EGFR mutations and EML4-alk translocations has been well-described, there is limited information about the impact of these somatic mutations on response to chemotherapy. Methods: We retrospectively reviewed the demographics and clinical outcomes of patients with KRAS mutations and compared these to patients who were KRAS wild-type (WT). Eligible pts received 1st-line IV chemo for stage IV NSCLC at DFCI and had known information about both KRAS and EGFR status. Since the biology and impact of EGFR mutations on response to chemo is well-described, we excluded such pts from the analysis. The primary endpoint was progression-free survival (PFS) with first-line chemo; secondary endpoints included radiographic response rate (RR) and overall survival (OS). Results: Between 2/05 and 8/11, there were 63 eligible KRAS pts and 97 eligible WT pts. The groups were similar in age (median 65yrs in both groups), % female (K 62, WT 54) race (K 89% white/6% black, 5% other; WT 86% white,/6% black/8% other), histology (K 90%adeno/8% NSCLC NOS; WT 86% adeno/9%NSCLC NOS), and % of pts receiving 1/2/3 agents in 1st line (K 11/56/33; WT 18/53/30). KRAS pts were less likely to be never or light smokers (4% vs 33% for WT). Nonsmokers were more likely to harbor KRAS transition rather than transversion mutations (3 transition, 1 transversion), while the converse held for smokers (51 transversions, 8 transitions). Median PFS was similar for KRAS vs WT (K .65 vs WT 4.8 months, p=0.81). RR (29% for both groups), disease control rates (K 73% vs WT 78%), and median OS (K 13.5 vs WT 12.1 months, p=.525) were also similar. Outcomes of KRAS pts to 2nd line chemotherapy (PFS 2.2, OS 8.6) are similar to those seen for WT patients in this setting. There was no significant difference in outcomes based on gender, smoking status, drug received (pemetrexed-based vs taxane based), or specific KRAS genotype. Conclusions: Pts with KRAS mutations experience similar outcomes to standard chemotherapy as those who are wild-type for EGFR and KRAS. Going forward, these data can serve as a reference for control arms of KRAS-specific randomized trials.

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