scholarly journals Changes in the concentration of EGFR-mutated plasma DNA in the first hours of anti-EGFR therapy allow the prediction of tumor response in patients with EGFR-driven lung cancer

2021 ◽  
Vol 67 (5) ◽  
pp. 665-674
Author(s):  
Aleksandr S Martianov ◽  
Fedor Moiseenko ◽  
Albina Zhabina ◽  
Tatyana Sokolova ◽  
Sergey Beluhin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Disease Control ◽  
Kinase Inhibitors ◽  
Tumor Response ◽  
Objective Response ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Plasma Dna ◽  
Egfr Mutant ◽  
Egfr Mutated

This study aimed to analyze changes in the plasma concentration of EGFR-mutated DNA occurring immediately after the start of therapy with EGFR tyrosine kinase inhibitors (TKIs). The study included 30 patients with EGFR mutation-driven non-small cell lung cancer (NSCLC).  Serial plasma samples were collected before intake of the first tablet and at 0.5, 1, 2, 3, 6, 12, 24, 36 and 48 hours after the start of the therapy. EGFR-mutated plasma DNA (EGFR+ ctDNA) was detectable at diagnosis in 25 out of 30 study participants. There were different patterns of changes of the amount of circulating tumor DNA, i.e., the consistent decline of ctDNA content, or continuing increase of the number of circulating EGFR mutant copies, or alternating spikes and drops in the ctDNA concentration. Correlation with the disease outcome was observed only for the measurement performed at 48 hours. Twelve (50%) out of 24 informative patients showed >25% reduction of the ctDNA content at 48 h time point; all these patients demonstrated disease control after 4 and 8-12 weeks of therapy. The remaining 12 individuals showed either stable content of circulating EGFR+ DNA (n = 5) or the elevation of ctDNA concentration (n = 7). 10 of 12 patients with elevated or stable ctDNA level achieved an objective response at 4 weeks, but only 5 of 10 evaluable patients still demonstrated disease control at 8-12 weeks (p = 0.014, when compared to the group with ctDNA decrease). The decline of the amount of circulating EGFR mutant copies also correlated with longer progression-free survival (PFS; 14.7 months vs. 8.5 months, p = 0.013). Conclusion: Monitoring of plasma EGFR-M+ concentration within the first hours of the TKI therapy may be used as an immediate predictor of tumor response to the treatment. 

scholarly journals Prognostic Value of BIM Deletion in EGFR-Mutant NSCLC Patients Treated with EGFR-TKIs: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Fangfang Lv ◽  
Liang Sun ◽  
Qiuping Yang ◽  
Zheng Pan ◽  
Yuhua Zhang
Keyword(s):  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Deletion Polymorphism ◽  
Asian Populations ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

Background. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable in EGFR-mutant non-small-cell lung cancer (NSCLC) patients. A germline 2903 bp deletion polymorphism of Bcl-2-like protein 11 (BIM) causes reduced expression of proapoptotic BH3-only BIM protein and blocks TKI-induced apoptosis of tumor cells. Yet the association between the deletion polymorphism and response to EGFR-TKI treatment remains inconsistent among clinical observations. Thus, we performed the present meta-analysis. Methods. Eligible studies were identified by searching PubMed, Embase, and ClinicalTrials.gov databases prior to March 31, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) and 95% CIs of objective response rate (ORR) and disease control rate (DCR) were calculated by using a random effects model. Sensitivity, metaregression, and publication bias analyses were also performed. Results. A total of 20 datasets (3003 EGFR-mutant NSCLC patients receiving EGFR-TKIs from 18 studies) were included. There were 475 (15.8%) patients having the 2903-bp intron deletion of BIM and 2528 (84.2%) wild-type patients. BIM deletion predicted significantly shorter PFS ( HR = 1.35 , 95% CI: 1.10-1.64, P = 0.003 ) and a tendency toward an unfavorable OS ( HR = 1.22 , 95% CI: 0.99-1.50, P = 0.068 ). Patients with deletion polymorphism had lower ORR ( OR = 0.60 , 95% CI: 0.42-0.85, P = 0.004 ) and DCR ( OR = 0.59 , 95% CI: 0.38-0.90, P = 0.014 ) compared with those without deletion. Conclusion. BIM deletion polymorphism may confer resistance to EGFR-TKIs and can be used as a biomarker to predict treatment response to EGFR-TKIs in EGFR-mutant NSCLC patients from Asian populations.

Local ablative therapy (LAT) for oligoprogressive, EGFR-mutant, non-small cell lung cancer (NSCLC) after treatment with osimertinib.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20545-e20545 ◽  
Author(s):  
Chul Kim ◽  
Nitin Roper ◽  
Chuong D. Hoang ◽  
Eva Szabo ◽  
Maureen Connolly ◽  
...  
Keyword(s):  
Disease Progression ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
T790m Mutation ◽  
Tki Treatment ◽  
Egfr Mutant ◽  
A Prospective Study ◽  
Egfr Tki ◽  
Egfr Tkis

e20545 Background: EGFR tyrosine kinase inhibitors (EGFR-TKIs) improve progression-free survival (PFS) in patients with EGFR-mutant NSCLC, but disease progression limits efficacy. Retrospective studies show a survival benefit to LAT in patients with oligoprogressive disease (progression at a limited number of anatomic sites). Methods: This is a prospective study of LAT in patients with oligoprogressive EGFR-mutant NSCLC. Patients with no prior EGFR-TKI therapy (cohort 1) or progression after 1st/2ndgeneration EGFR-TKIs with acquired T790M mutation (cohort 2) receive osimertinib. Upon progression, eligible patients with < = 5 progressing sites undergo LAT and resume osimertinib until disease progression. Patients previously treated with osimertinib qualifying for LAT upon disease progression are also eligible for treatment (cohort 3). Primary endpoint: evaluation of safety and efficacy of reinitiation of osimertinib after LAT (assessed by PFS). Additional goals are assessment of mechanisms of resistance to osimertinib by multi-omics analyses of tumor, blood, and saliva. Results: Between 04/2016 and 01/2017, 15 patients were enrolled (cohort 1: 9, cohort 2: 3, cohort 3: 3). Median age was 57 (range 36-71). Treatment was well tolerated. The most common adverse events (AEs) were rash, diarrhea, thrombocytopenia, and alanine transaminase elevation. Grade 3/4 AEs were observed in 4 (27%) patients. Among evaluable patients, objective response rates prior to LAT in cohorts 1 and 2 were 71% (5/7) and 100% (2/2), respectively, with 6.8 months median PFS (95% CI: 3.4 months-undefined) in cohort 1 and no progressions in cohort 2. To date, 5 patients (33%; cohort 1: 2; cohort 3: 3) had LAT. Two patients with 3 progressing sites underwent a combination of surgery and radiation. Three patients with 1 progressing site underwent surgery alone. Post-LAT PFS and results of molecular analyses will be presented. Conclusions: Patients with EGFR-mutant NSCLC and oligoprogression after EGFR-TKI therapy can be safely treated with LAT. In selected patients, this approach could potentially maximize duration of EGFR-TKI treatment and prevent premature switching to other systemic therapies. Clinical trial information: NCT02759835.

scholarly journals Retrospective Analysis of Skin Toxicity in Patients under Anti-EGFR Tyrosine Kinase Inhibitors: Our Experience in Lung Cancer

2019 ◽  
Vol 7 (6) ◽  
pp. 973-977 ◽  
Author(s):  
Maria Carmela Annunziata ◽  
Maria Ferrillo ◽  
Eleonora Cinelli ◽  
Luigia Panariello ◽  
Danilo Rocco ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Skin Reaction ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Skin Reactions ◽  
Cutaneous Toxicity ◽  
Common Skin

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been introduced for the treatment of lung cancer, improving progression-free survival, objective response rate, and quality of life. However, TKIs can lead to cutaneous toxicities, including papulopustular rash, xerosis, paronychia with/without pyogenic granulomas, scalp disorders, facial hair and/or eyelash growth. AIM: In this study, we describe retrospectively all cases of mucocutaneous side effects in patients with lung cancer under TKIs referring to our outpatient for the skin care of oncological patients. METHODS: We included patients referring from January 2016 to January 2018 affected by lung cancer and under TKIs. We collected data about the clinical exam, clinical photography, dermoscopy, histology and direct microscopic examination for each patient and we performed retrospectively descriptive analyses to assess whether a specific TKIs is linked significantly to particular cutaneous toxicity. RESULTS: The majority of skin toxicities were due to afatinib, and the most common skin reaction was rash. We selected 60 patients with skin reactions, treated by TKIs for lung cancer. The majority of skin toxicities were due to afatinib (47/102 adverse reactions) and erlotinib (39/102). The most common skin reaction was rash (63% of patients), followed by xerosis (30%) and granulomas (30%). There was no significant relationship between a specific type of cutaneous reaction and specific EGFRi except for granulomas, developed more frequently in patients under afatinib (p < 0.05). CONCLUSION: Most of our patients (63%) developed a cutaneous rash under TKIs. Most commonly afatinib was the drug involved, although it wasn’t the most used EGFRi. Moreover, we noticed a significant correlation between afatinib therapy and appearance of granulomas.

scholarly journals Early identification of disease progression in ALK-rearranged lung cancer using circulating tumor DNA analysis

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Arlou Kristina Angeles ◽  
Petros Christopoulos ◽  
Zhao Yuan ◽  
Simone Bauer ◽  
Florian Janke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Disease Progression ◽  
Dna Analysis ◽  
Kinase Inhibitors ◽  
Acquired Resistance ◽  
Circulating Tumor Dna ◽  
Plasma Dna ◽  
Early Detection Of Disease ◽  
Targeted Next Generation Sequencing ◽  
Longitudinal Plasma

AbstractTargeted kinase inhibitors improve the prognosis of lung cancer patients with ALK alterations (ALK+). However, due to the emergence of acquired resistance and varied clinical trajectories, early detection of disease progression is warranted to guide patient management and therapy decisions. We utilized 343 longitudinal plasma DNA samples from 43 ALK+ NSCLC patients receiving ALK-directed therapies to determine molecular progression based on matched panel-based targeted next-generation sequencing (tNGS), and shallow whole-genome sequencing (sWGS). ALK-related alterations were detected in 22 out of 43 (51%) patients. Among 343 longitudinal plasma samples analyzed, 174 (51%) were ctDNA-positive. ALK variant and fusion kinetics generally reflected the disease course. Evidence for early molecular progression was observed in 19 patients (44%). Detection of ctDNA at therapy baseline indicated shorter times to progression compared to cases without mutations at baseline. In patients who succumbed to the disease, ctDNA levels were highly elevated towards the end of life. Our results demonstrate the potential utility of these NGS assays in the clinical management of ALK+ NSCLC.

Longitudinal monitoring by next generation sequencing of plasma cell-free DNA in ALK-rearranged non-small cell lung cancer (NSCLC) patients treated with ALK tyrosine kinase inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9603-9603 ◽  
Author(s):  
Minsuk Kwon ◽  
Bo Mi Ku ◽  
Sehhoon Park ◽  
Hyun Ae Jung ◽  
Jong-Mu Sun ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Next Generation ◽  
Resistance Mutations ◽  
Plasma Dna ◽  
Anaplastic Lymphoma ◽  
Free Plasma ◽  
Generation Sequencing

9603 Background: Patients with anaplastic lymphoma kinase-rearranged (ALK+) NSCLC inevitably acquire resistance to ALK inhibitors. We hypothesized that longitudinal monitoring of cell-free plasma DNA (cfDNA) next generation sequencing (NGS) could predict the response and resistance of TKI therapy in ALK+NSCLC Methods: Patients with ALK+ advanced NSCLC determined by standard tissue testing and planned for TKI therapy were prospectively recruited. Plasma was collected before therapy (n = 92), two months post-therapy (n = 58), and at progression (n = 35). Plasma DNA NGS analysis was done retrospectively by Guardant360. Results: From April 2015 to July 2019, 92 patients enrolled; 81 (88.0%) received ALK TKI as first-line (crizotinib, n = 59; alectinib, n = 22), 10 (10.9%) received TKI as second-line (alectinib, n = 6; crizotinib, n = 2; ceritinib, n = 1; brigatinib, n = 1), and 1 (1.1%) was treated in third-line (lorlatinib). At the cut-off date of January 28, 2020, 56 of 92 patients had disease progression. Circulating tumor DNA (ctDNA) was detected in 69 baseline samples (75%); among these were 43 ALK fusions (62.3%) and 1 ALK G1202R without fusion (1.4%). Fusions included EML4-ALK v1 (n = 19), EML4-ALK v3 (n = 14), CLTC-ALK (n = 1), TPM3-ALK (n = 1), GCC2-ALK/CLIP4-ALK (n = 1), and other EML4-ALK fusions (n = 7). Eight patients developed ALK resistance mutations after crizotinib therapy: L1196M (n = 5), G1269A (n = 1), G1202R (n = 1), and co-occurring F1174L, G1202R, and G1269A (n = 1). Two patients developed ALK resistance mutations after ceritinib: G1202R (n = 1), and co-occurring G1202R and T1151R (n = 1). The absence of detectable ctDNA at baseline was associated with longer progression-free survival (PFS; median 36.1 vs 11.6 months, HR 0.432, p = 0.004) and overall survival (OS; median not reached vs 27.9 months, HR 0.418, p = 0.034). Patients with clearance of ctDNA at two months (n = 29) had significantly longer PFS (median 25.4 vs 13.9 months, HR 0.343, p = 0.030) and OS (median not reached vs 25.7 months, HR 0.173, p = 0.035) than those without clearance (n = 22). Patients with co-occurring TP53 alterations and ALK fusions at baseline (n = 9) showed shorter PFS (median 7.0 vs 12.5 months, HR 3.596, p = 0.0154) than those without TP53 alterations (n = 35). Conclusions: NGS of cell-free plasma DNA is useful not only for the detection of ALK fusions and resistance mutations but also for assessing prognosis and monitoring the dynamic changes of genomic alterations in ALK+ NSCLC treated with ALK TKI.

scholarly journals Complex ALK Fusions Are Associated With Better Prognosis in Advanced Non-Small Cell Lung Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Jin Kang ◽  
Xu-Chao Zhang ◽  
Hua-Jun Chen ◽  
Wen-Zhao Zhong ◽  
Yang Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Small Cell ◽  
Fusion Partner ◽  
Small Cell Lung ◽  
Anaplastic Lymphoma

BackgroundEchinoderm microtubule-associated protein-like 4 (EML4) is the canonical anaplastic lymphoma kinase (ALK) fusion partner in non-small cell lung cancer (NSCLC), and ALK-positive patients showed promising responses to ALK tyrosine kinase inhibitors (TKIs). However, studies that comprehensively investigate ALK TKI treatment in patients with different ALK fusion patterns are still lacking.MethodsNinety-eight ALK-positive patients with advanced NSCLC were retrospectively studied for their response to crizotinib and subsequent treatments. Comprehensive genomic profiling (CGP) was conducted to divide patients into different groups based on their ALK fusion patterns. Non-canonical ALK fusions were validated using RNA-sequencing.Results54.1% of patients had pure canonical EML4-ALK fusions, 19.4% carried only non-canonical ALK fusions, and 26.5% harbored complex ALK fusions with coexisting canonical and non-canonical ALK fusions. The objective response rate and median progression-free survival to crizotinib treatment tended to be better in the complex ALK fusion group. Notably, patients with complex ALK fusions had significantly improved overall survival after crizotinib treatment (p = 0.012), especially when compared with the pure canonical EML4-ALK fusion group (p = 0.010). The complex ALK fusion group also tended to respond better to next-generation ALK TKIs, which were used as later-line therapies. Most identified non-canonical ALK fusions were likely to be expressed in tumors, and some of them formed canonical EML4-ALK transcripts during mRNA maturation.ConclusionOur results suggest NSCLC patients with complex ALK fusions could potentially have better treatment outcomes to ALK TKIs therapy. Also, diagnosis using CGP is of great value to identify novel ALK fusions and predict prognosis.

scholarly journals Management of EGFR mutated nonsmall cell lung carcinoma patients

2015 ◽  
Vol 45 (4) ◽  
pp. 1132-1141 ◽  
Author(s):  
Bogdan Grigoriu ◽  
Thierry Berghmans ◽  
Anne-Pascale Meert
Keyword(s):  
Lung Cancer ◽  
Conformational Changes ◽  
Kinase Inhibitors ◽  
Catalytic Domain ◽  
Progression Free Survival ◽  
European Medicines Agency ◽  
Cell Lung Carcinoma ◽  
Unselected Population ◽  
Egfr Mutated ◽  
Egfr Tki

Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) are common in the therapeutic armentarium of lung cancer today. Initially tested in an unselected population, they have been of limited usefulness until the identification EGFR gene mutations. Activating mutations generate conformational changes that result in a shift toward an active state of the catalytic domain and are associated with sensitivity to first generation EGFR TKI. Other mutations have been associated with resistance to these drugs, but for rare mutations there is limited data concerning their role in predicting response to EGFR TKI.To date, four molecules have been approved for the treatment of EGFR mutated lung cancer. Gefitinib and/or erlotinib are available in almost all countries. Afatinib has been approved by the US Food and Drug Administration and by the European Medicines Agency, and icotinib has been approved only in China. Other, more active, third generation agents with a higher binding affinity for the receptor, or that are directed against specific mutations, are under development. EGFR TKIs have a favourable impact on progression-free survival when given as first line treatment in mutated patients, but may also have a moderate effect as a salvage therapy and in maintenance in an unselected population.

scholarly journals CNS Response to Osimertinib Versus Standard Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients With Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer

2018 ◽  
Vol 36 (33) ◽  
pp. 3290-3297 ◽  
Author(s):  
Thanyanan Reungwetwattana ◽  
Kazuhiko Nakagawa ◽  
Byoung Chul Cho ◽  
Manuel Cobo ◽  
Eun Kyung Cho ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutated ◽  
Cns Lesions ◽  
Egfr Tkis

Purpose We report CNS efficacy of osimertinib versus standard epidermal growth factor receptor ( EGFR) tyrosine kinase inhibitors (TKIs) in patients with untreated EGFR-mutated advanced non–small-cell lung cancer from the phase III FLAURA study. Patients and Methods Patients (N = 556) were randomly assigned to osimertinib or standard EGFR-TKIs (gefitinib or erlotinib); brain scans were not mandated unless clinically indicated. Patients with asymptomatic or stable CNS metastases were included. In patients with symptomatic CNS metastases, neurologic status was required to be stable for ≥ 2 weeks after completion of definitive therapy and corticosteroids. A preplanned subgroup analysis with CNS progression-free survival as primary objective was conducted in patients with measurable and/or nonmeasurable CNS lesions on baseline brain scan by blinded independent central neuroradiologic review. The CNS evaluable-for-response set included patients with ≥ one measurable CNS lesion. Results Of 200 patients with available brain scans at baseline, 128 (osimertinib, n = 61; standard EGFR-TKIs, n = 67) had measurable and/or nonmeasurable CNS lesions, including 41 patients (osimertinib, n = 22; standard EGFR-TKIs, n = 19) with ≥ one measurable CNS lesion. Median CNS progression-free survival in patients with measurable and/or nonmeasurable CNS lesions was not reached with osimertinib (95% CI, 16.5 months to not calculable) and 13.9 months (95% CI, 8.3 months to not calculable) with standard EGFR-TKIs (hazard ratio, 0.48; 95% CI, 0.26 to 0.86; P = .014 [nominally statistically significant]). CNS objective response rates were 91% and 68% in patients with ≥ one measurable CNS lesion (odds ratio, 4.6; 95% CI, 0.9 to 34.9; P = .066) and 66% and 43% in patients with measurable and/or nonmeasurable CNS lesions (odds ratio, 2.5; 95% CI, 1.2 to 5.2; P = .011) treated with osimertinib and standard EGFR-TKIs, respectively. Probability of experiencing a CNS progression event was consistently lower with osimertinib versus standard EGFR-TKIs. Conclusion Osimertinib has CNS efficacy in patients with untreated EGFR-mutated non–small-cell lung cancer. These results suggest a reduced risk of CNS progression with osimertinib versus standard EGFR-TKIs.

scholarly journals Retrospective study on the clinicogenomic characteristics of EGFR mutant and wildtype NSCLC

2020 ◽  
Author(s):  
Chirag Dhar
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Receptor Gene ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Asian Ethnicity ◽  
Lung Cancers ◽  
Cohort Study Design ◽  
Underlying Mechanisms ◽  
Egfr Mutant

Background: Lung cancer is among the leading causes of mortality. Nearly 90% of all lung cancers are histologically classified as non-small cell lung cancer (NSCLC). A subset of these tumors harbor mutations on the epidermal growth factor receptor gene (EGFR) and such patients are candidates for targeted therapy with EGFR tyrosine kinase inhibitors (EGFR TKIs). Aim: To compare and contrast the clinicogenomic characteristics of EGFR mutant and wildtype NSCLC. Methods and results: A retrospective cohort study design was used to analyze publicly available data on cBioPortal.org. Patients with EGFR mutations were more likely to be, female; of Asian ethnicity; never-smokers and diagnosed with lung adenocarcinoma. Metastasis to, the pleura; pleural fluid and liver were common in patients with EGFR mutant NSCLC. On the other hand, lymph node, brain and adrenal gland metastases were more common in patients with other mutations. While the median overall survival was about the same in the two groups, progression free survival was significantly shorter in the EGFR mutant group. The mutational landscape was significantly different in the two groups with EGFR mutant NSCLCs having a lower mutational burden. Differences in copy number alterations between the two groups were also noted. Conclusions: The clinicogenomic profiles of EGFR mutant and wildtype significantly differ. Further studies on these differences and underlying mechanisms are likely to lead to new druggable targets that overcome EGFR TKI resistance.

Crizotinib for c-MET–amplified advanced NSCLC: a single-center experience

2021 ◽  
pp. 030089162110093
Author(s):  
Seher Yildiz Tacar ◽  
Mesut Yilmaz ◽  
Buge Oz ◽  
Deniz Tural
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Driver Mutations ◽  
Effective Treatment Option ◽  
Met Amplification ◽  
Number Of Patients

Introduction: Lung cancer is the most common cause of cancer-related death in the world. Changes in the treatment of metastatic lung cancer in recent years have made targetable mutations gain importance. MET alteration is one of these driver mutations and crizotinib is a tyrosine kinase inhibitor used in therapy. Methods: In our study, data of patients with c-MET amplification who received crizotinib treatment between July 2017 and November 2020 in the Medical Oncology Clinic of Bakırköy Dr. Sadi Konuk Training and Research Hospital were retrospectively analyzed. c-MET scanning was performed by the fluorescent in situ hybridization method by using Cytotest MET/CCP7 probe kit by evaluating 100 tumor cells and the threshold value for positivity was accepted as above 20%. Results: Eight of 28 patients who received crizotinib treatment had c-MET amplification. Seven of these patients were male and one was female. Progression-free survival and overall survival in these eight patients were 9.4 and 10.9 months, respectively, and objective response rate was 50%. Grade 4 nausea was observed in only one patient; there was no grade 4–5 toxicity and no patient discontinued the drug due to toxicity. Conclusion: Crizotinib is an effective treatment option other than cytotoxic chemotherapy in the limited number of patients with MET amplification in the stage 4 lung adenocarcinoma subgroup. It is important to investigate this amplification, which can be detected especially in smoking patients in the appropriate patient group, and to use appropriate tyrosine kinase inhibitors in treatment.

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