Advanced Stage Non-small Cell Lung Research Articles

Real-world evidence for pembrolizumab in non-small cell lung cancer: a nationwide cohort study.

Based on favourable results from clinical trials, immune checkpoint inhibitors (ICI) have become the standard first line (1 L) systemic anticancer treatment (SACT) for advanced stage non-small cell lung cancer (NSCLC) without targetable mutations. We evaluate whether these results are generalizable to everyday clinical practice and compare overall survival (OS) of patients treated with ICI to a historical cohort of patients treated with chemotherapy and results from clinical trials. Our study comprised all advanced NSCLC patients initiating SACT in 2012-21 in Norway. Clinical characteristics and treatment information was retrieved from Norwegian Health Registries. Survival for all 8416 advanced NSCLC patients treated with SACT increased concurrently with the gradual implementation of ICIs. Median OS of patients treated with 1 L pembrolizumab after 2017 was better (mono-/combination therapy: 13.8/12.8 months) than for patients treated with chemotherapy before 2017 (8.0 months). Although median OS for patients treated with pembrolizumab was lower in clinical practice than clinical trials (Keynote-024/189: 26.3/22.0 months), the survival benefit relative to chemotherapy was similar. Our nationwide study demonstrated a survival benefit over conventional chemotherapy of a similar magnitude as observed in clinical trials and confirms the effectiveness of pembrolizumab in routine clinical practice.

Clinical value of comprehensive genomic profiling on clinical trial enrollment for patients with advanced solid tumors.

The use of biomarker testing to inform treatment decisions has emerged as a standard of care in multiple cancer types. However, the rates of patients with genomic testing results in hand to inform treatment decision-making remain variable. Here, we studied the impact of comprehensive genomic profiling (CGP) on clinical trial enrollment rates in patients with advanced-stage non-small cell lung, colorectal, breast, and prostate cancer using a real-world clinicogenomic database. On average, clinical trial enrollment in the therapy line immediately after CGP report receipt was 5.4%, which represents a 3.0 percentage point increase compared to therapy lines preceding CGP report receipt, supporting a meaningful association between CGP report availability and increased clinical trial enrollment.

An updated overview of K-RAS G12C inhibitors in advanced stage non-small cell lung cancer.

The discovery of KRAS mutations, particularly the KRASG12C variant, has been a milestone in understanding the molecular underpinnings of non-small cell lung cancer (NSCLC). These mutations are associated with aggressive tumor behavior and resistance to conventional therapies, highlighting the urgent need for targeted interventions. In this comprehensive review, we analyze the advancements in KRAS G12C inhibitors for the treatment of non-small cell lung cancer. Literature search is made from PubMed, Medline ASCO and ESMO Annual Meetings abstracts by using the following search keywords: "sotorasib", "adagrasib", "divarasib" and "KRAS G12C inhibitors." The last search was on 5June 2024. This review highlights the importance of pharmacokinetics, pharmacodynamics and potential adverse effects for treating individual patients and ensuring the best outcomes. Additionally, the review discusses research identifying biomarkers that can predict therapy responses and mentions the combination strategies to overcome resistance. Results of the studies and ongoing clinical trials are also briefly summarized in this review. KRASG12C inhibitors sotorasib, adagrasib and the newer divarasib, has revolutionized treating patients harboring this mutation. Ongoing studies and future clinical trials will refine our understandings with the ultimate goal of improving survival and quality of life for patients with this challenging disease.

1304P Investigator-initiated study of crizotinib in patients with MET activated advanced stage non-small cell lung cancer: A Canadian experience

1304P Investigator-initiated study of crizotinib in patients with MET activated advanced stage non-small cell lung cancer: A Canadian experience

Blood based kinase activity profiling to predict response to immune checkpoint inhibitors in patients with advanced stage non-small cell lung cancer: The IOpener study.

e20576 Background: Treatment with immune checkpoint inhibitors (ICI) has become part of the standard of care for patients with advanced stage non-small cell lung cancer (NSCLC). Unfortunately, its success is limited to a subset of treated patients, while ICI treatment is associated with immune-related adverse events. The predictive value of kinase activity profiling of peripheral blood mononuclear cells (PBMCs) was previously shown in a discovery study (Hurkmans et al., JITC 2020). The aim of the current study was to perform a prospective and blinded validation of the predictive value of kinase activity profiles of PBMCs for response to ICI treatment in patients with NSCLC in a standardized setting. Preliminary results for this study were presented before (De Joode et al. 2022), here we present results for a significantly extended validation cohort with a follow-up of at least 1 year. Methods: PBMCs from patients with advanced stage NSCLC included in this observational multicenter study were collected prior to ICI treatment. Tyrosine kinase activity of PBMCs was profiled using a micro-array with 144 different peptide-substrates (Pamchip). Classification analysis was performed to discriminate between patients with or without progressive disease (RECIST v1.1) within 24 weeks after start of treatment. Only patients treated with first-line pembrolizumab ± chemotherapy were included. Results: A predictive model was first established based on kinase activity profiles, determined in a calibration cohort (N = 61) and subsequently applied to an independent validation cohort (N = 136). The predictive accuracy of the model in the validation cohort was 62% (CI95 = 53-70%). Interestingly, the accuracy improved when the model was combined with PD-L1 expression: for patients with a PD-L1 score < 50%, the accuracy for predicting progressive disease at 24 weeks was 68% (CI95 = 57-78%). Here, significant lower progression free survival (PFS) rates were observed for patients for whom progression was predicted compared to those for whom no progression was predicted (p = 0.0003, hazard ratio = 2.6, CI95 = 1.6-4.3).The 1-year PFS for patients with predicted progression was only 13% (CI95 = 5-31%) which implies a NPV of 87%. PFS rates were also lower for patients with predicted progression in the subgroups with PD-L1 score < 1% (p = 0.03, hazard ratio = 2.2, CI95 = 1.1-4.3) and PD-L1 score 1-49% (p = 0.002, hazard ratio = 5.0, CI95 = 1.8-14). The predictive kinase activity signature appears to be T-cell related, which will be further investigated to improve understanding of the underlying biology. Conclusions: In this prospective validation study the predictive value of kinase activity profiling of PBMCs for response to first-line ICI therapy of patients with advanced NSCLC was confirmed. The final aim is to apply the kinome analysis in clinical practice.

Abstract 2526: Exploratory study of predicting systemic therapy response by IGRA in advanced stage NSCLC patients

Abstract Purpose: In this study, we aim to prospectively evaluate how patients’ pretreatment PSIG correlated with chemotherapy, immune checkpoint inhibitors (ICI) and epidermal growth factor receptor (EGFR) Tyrosine Kinasae Inhibior (TKI). Also, to assess the change of PSIG during anti-cancer treatment and the relation with clinical condition. Materials and Methods: Newly diagnosed advanced stage non-small cell lung cancer patients were enrolled. The inclusion criteria included pathology or cytology-proved stage IV and non-operable stage III non-small cell lung cancer, treatment-naïve, and planned to receive chemotherapy, EGFR-TKI therapy. Or, planned to receive any line of singe agent immunotherapy. We planned to enroll 30 patients in each treatment group (chemotherapy, immunotherapy, EGFR TKI therapy) with and additional control group of stage I NSCLC.Blood sample from each enrolled patient was obtained for INF-γ release assay (IGRA) within 3 days before the initiation of systemic therapy and 8-12 weeks after treatment. The IGRA was performed with QuantiFERON-TB In-Tube (QFT-GIT; Qiagen, Germany) according to the manufacture’s instruction. The amount of INF-γ produced in response to PHA is determined by the INF-γ level in the PHA-coated tube minus saline-coated tube, and is termed PHA-stimulated INF-γ (PSIG) level. Patients with PSIG level above 7.06IU were defined had high PSIG level according to our previous study. we also performed our in house INF-γ level by ELISA. Tumor response was assessed mainly by chest CT and brain MRI (if available) according to Response Evaluation Criteria in Solid Tumors (RECST). Results: Total 116 patients were enrolled. Demographic distribution was summarized in Table 1. Thirty-five of 116 (30.2%) patients had latent TB infection, while 12 patients (10.3%) had indeterminate OFT test, all due to low mitogen-stimulated INF-γ level. 84 patients had been obtained post-treatment blood test, and the box-plot of in-house INF-γ level were shown in Figure1. For stage I control group, INF-γ level seemed higher after surgery; for chemotherapy and immunotherapy, the INF-γ level also seemed increase among responders (who achieved disease control after treatment). There were no statistically difference of disease control rate between patients with high PSIG level and low PSIG level. Overall survival also showed no statistically difference between 2 PSIV level patient group among advanced stage NSCLC patients. Conclusions:There were no statistically different of disease control rate in PSIG high and low group. The increased trend of INF-γ level after surgery, immunotherapy and chemotherapy may suggested improving immune function after treatment even in the very early disease stage. Citation Format: Hsu Ching Huang, Chi-Lu Chiang, Yung-Hung Luo, Yuh-Min Chen, Chao-Hua Chiu. Exploratory study of predicting systemic therapy response by IGRA in advanced stage NSCLC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2526.

Circulating miR-10b, soluble urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 as predictors of non-small cell lung cancer progression and treatment response.

Despite advances in lung cancer treatment, most lung cancers are diagnosed at an advanced stage. Expression of microRNA10b (miR-10b) and fibrinolytic activity, as reflected by soluble urokinase-type plasminogen activator receptor (suPAR) and plasminogen activator inhibitor 1 (PAI-1), are promising biomarker candidates. To assess the expression of miR-10b, and serum levels of suPAR and PAI-1 in advanced stage non-small cell lung cancer (NSCLC) patients, and their correlation with progression, treatment response and prognosis. The present prospective cohort and survival study was conducted at Dharmais National Cancer Hospital and included advanced stage NSCLC patients diagnosed between March 2015 and September 2016. Expression of miR-10b was quantified using qRT-PCR. Levels of suPAR and PAI-1 were assayed using ELISA. Treatment response was evaluated using the RECIST 1.1 criteria. Patients were followed up until death or at least 1 year after treatment. Among the 40 patients enrolled, 25 completed at least four cycles of chemotherapy and 15 patients died during treatment. Absolute miR-10b expression ⩾ 592,145 copies/μL or miR-10b fold change ⩾ 0.066 were protective for progressive disease and poor treatment response, whereas suPAR levels ⩾ 4,237 pg/mL was a risk factor for progressive disease and poor response. PAI-1 levels > 4.6ng/mL was a protective factor for poor response. Multivariate analysis revealed suPAR as an independent risk factor for progression (ORa⁢d⁢j, 13.265; 95% confidence intervals (CI), 2.26577.701; P= 0.006) and poor response (ORa⁢d⁢j, 15.609; 95% CI, 2.221-109.704; P= 0.006), whereas PAI-1 was an independent protective factor of poor response (ORa⁢d⁢j, 0.127; 95% CI, 0.019-0.843; P= 0.033). Since miR-10b cannot be used as an independent risk factor for NSCLC progression and treatment response, we developed a model to predict progression using suPAR levels and treatment response using suPAR and PAI-1 levels. Further studies are needed to validate this model.

The Role of Immune-Inflammation Biomarkers to Predict the Response of Nivolumab in Second Line Treatment of Advanced Stage Non-Small Cell Lung Cancer

The Role of Immune-Inflammation Biomarkers to Predict the Response of Nivolumab in Second Line Treatment of Advanced Stage Non-Small Cell Lung Cancer

7P A T cell-derived circulating DNA as a biomarker for response to anti-PD(L)1 immunotherapy in advanced stage non-small cell lung cancer

7P A T cell-derived circulating DNA as a biomarker for response to anti-PD(L)1 immunotherapy in advanced stage non-small cell lung cancer

P2.09-12 Real World Analysis Afatinib as a First Line Treatment Patients with Advanced Stage Non-small Cell Lung Cancer Harboring Uncommon EGFR Mutations

P2.09-12 Real World Analysis Afatinib as a First Line Treatment Patients with Advanced Stage Non-small Cell Lung Cancer Harboring Uncommon EGFR Mutations

EP10.01-16 Relationship between Impaired Fasting Glucose and Prognosis of the Disease in Patients with Advanced Stage Non-small Cell Lung Cancer.

EP10.01-16 Relationship between Impaired Fasting Glucose and Prognosis of the Disease in Patients with Advanced Stage Non-small Cell Lung Cancer.

Survival Evaluation in Patients Over 70 Years of Age With Advanced Stage Non-small Cell Lung Cancer

Survival Evaluation in Patients Over 70 Years of Age With Advanced Stage Non-small Cell Lung Cancer

Prognostic Value of Nivolumab Clearance in Non-Small Cell Lung Cancer Patients for Survival Early in Treatment.

Immune checkpoint inhibitors improved survival of advanced stage non-small cell lung cancer patients, but the overall response rate remains low. A biomarker that identifies non-responders would be helpful to allow treatment decisions. Clearance of immune checkpoint inhibitors is related to treatment response, but its prognostic potential early in treatment remains unknown. Our primary aim was to investigate the prognostic potential of nivolumab clearance for overall survival early in treatment. Our secondary aim was to evaluate the performance of nivolumab clearance as prognostic biomarker. Individual estimates of nivolumab clearances at first dose, 6 and 12 weeks after treatment initiation were obtained via nonlinear mixed-effects modelling. Prognostic value of nivolumab clearance was estimated using univariate Cox regression at first dose and for the ratios between 6 and 12 weeks to first dose. The performance of nivolumab clearance as biomarker was assessed by calculating sensitivity and specificity. During follow-up of 75 months, 69 patients were included and 865 died. Patients with a nivolumab clearance ≥ 7.3 mL/h at first dose were more likely to die compared to patients with a nivolumab clearance < 7.3 mL/h at first dose (hazard ratio [HR] = 3.55, 955 CI 1.75-7.20). The HRs of dose nivolumab clearance ratios showed similar results with a HR of 3.93 (955 CI 1.66-9.32) for 6 weeks to first-dose clearance ratio at a 0.953 cut-point and a HR of 2.96 (955 CI 1.32-6.64) for 12 weeks to first-dose clearance ratio at a cut-point of 0.814. For nivolumab clearance at all early time points, sensitivity was high (≥ 0.95) but specificity was low (0.11-0.29). Nivolumab clearance is indicative of survival early in treatment. Our results encourage to further assess the prognostic potential of immunotherapy clearance.

Impact of Waiting Times on Mortality in Advanced Stage Non-Small Cell Lung Cancer: A 10-Year Retrospective Cohort Study in Thailand.

This study investigated the relationship between mortality and waiting times from diagnosis to first treatment while also considering other important risk factors associated with mortality. This is a cohort study including 497 patients diagnosed with advanced stage non-small cell lung cancer (NSCLC) between 1st January 2012 and 31st December 2021. The risk factors and waiting periods were analysed to determine their association with mortality. The waiting periods were recorded based on the timeline of patient visits, including the time between the 1st visit and imaging, the time between the 1st visit and tissue diagnosis, the time between the procedure and tissue diagnosis, the time between tissue diagnosis and treatment and the time from the 1st visit until treatment. The data were assessed using Cox regression with time-varying covariates. Waiting time for tissue diagnosis had a modest effect on mortality, a waiting time of more than four weeks indicated poor prognosis both in univariate and multivariate analyses [HR 1.48 (95%CI 1.18-1.87), p = < 0.01), adjusted HR 1.007 (95%CI 1.002-1.010), p = 0.02]. Waiting time for other services was not shown to be associated with mortality. The mortality rate was 3 times higher in patients with poor ECOG performance status than good ECOG performance [adjusted HR 3.17(2.04-4.91)]. Patients with EGFR sensitizing mutation who were treated with EGFR TKI therapy had a lower risk of lung cancer death compared to those being treated with chemotherapy [adjusted HR 0.49 (0.33-0.72)]. Molecular testing for EGFR sensitizing mutation and the TKI treatment were fundamental changes that assisted in improving survival rates for patients diagnosed with advanced stage lung cancer over the 10-year period. However, poor ECOG performance status remained a strong risk factor for lung cancer death. Longer waiting time for tissue diagnosis might indicate a poor prognosis.

59P Correlation of tumor microenvironment signature in advanced stage non-small cell lung cancer with EGFR mutation who received EGFR-TKIs

59P Correlation of tumor microenvironment signature in advanced stage non-small cell lung cancer with EGFR mutation who received EGFR-TKIs

Les CBNPC de stades avancés hors addiction oncogénique : les traitements systémiques de deuxième ligne: Advanced stage NSCLC excluding oncogenic addiction: second-line systemic treatments

The emergence of immunotherapy as the cornerstone of first line therapy in advanced stage Non-Small Cell Lung Cancer (NSCLC), without oncogenic driver, has led to change the treatment algorithm of second line, which was previously and mainly based on anti-PD(L)-1 given as a single agent. Second-line treatment is currently based on chemotherapy, with a platinumbased doublet for patients treated in first line by pembrolizumab alone, and standard second-line chemotherapy options for patients treated by chemotherapy-immunotherapy combinations, i.e. docétaxel regardless of histology or pemetrexed for non-squamous cell carcinoma when not used in first line. Addition of an antiangiogenic agent to taxane only achieved a modest improvement of overall survival. The future of second line treatment would require a better knowledge and understanding of resistance mechanisms to anti-PD(L)-1, and randomized phase III clinical trials, in order to optimize therapeutic options, including or not a rechallenge to an immunotherapy, targeting to restore anti-tumour immune response. Antibody drug-conjugate seem to be also a promising approach in this setting.1877-1203/© 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Mapping the clinical care pathways for advanced stage non-small cell lung cancer patients in Victoria: A retrospective cohort study of supportive and palliative care.

The lung cancer Optimal Care Pathway recommends supportive care and palliative care integration throughout its various steps, with early referral to appropriate services improving the quality of life in advanced stage non-small cell lung cancer patients. Using Victorian Lung Cancer Registry data and linked administrative datasets, this retrospective cohort study mapped clinical care pathways of 525 Stage III-IV non-small cell lung cancer patients in Victoria to 11 recommendations in the Optimal Care Pathway, identifying unwarranted variations in clinical care. Supportive care and palliative care delivery were further examined to understand the involvement and timing of specialist care teams. Our findings showed that palliative care utilization is highest at the time of treatment, despite recommendations that it should be provided early after diagnosis to improve patient outcomes and satisfaction. Early supportive care screening was observed in half the cohort and almost three-quarters of the patients had been presented at a multidisciplinary meeting. Multidisciplinary meeting presentations and supportive care provide an opportunity to improve communication about palliative care needs and integration into routine clinical practice, such as at the time of treatment planning.

Integrating POLE/POLD1 mutated for immunotherapy treatment planning of advanced stage non-small cell lung cancer.

In this study, we evaluated the potential of DNA polymerase epsilon (POLE) and DNA polymerase delta 1 (POLD1) as prognostic biomarkers for immune checkpoint inhibitor (ICI) treatment in patients with advanced stage non-small cell lung cancer (NSCLC). Disease stage, PD-L1 positivity, histological subtypes, POLE/POLD1 mutation status, tumor mutation burden (TMB), and response to ICIs in NSCLC cases were derived from AACR GENIE dataset (n = 24 120), TCGA-Pan Lung Cancer dataset (n = 1144), AACR GENIE BPC NSCLC v2.0-public (n = 2004), and Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets dataset (n = 350). The smoking history from TCGA and AACR GENIE datasets was grouped into current, former or never-smokers. POLE and POLD1 genetic alterations were identified in 5% and 2.6% of NSCLC patients, respectively. Current smokers had 9% and 4% of POLE/POLD1 mutations, respectively, versus 1.7% for both POLE and POLD1 mutations prevalence in never-smokers. POLE/POLD1 mutations were associated with elevated mutation counts than those with wild-type (median mutation counts 16 vs. 7, p < 0.0001), more advanced disease stages (stage I disease 15.19% vs. 29.42%), more prevalent squamous histology subtype (21.69% vs. 9.05%, p = 0.0427), and a higher percentage of PD-L1 positivity (66.67% vs. 43.87%, p < 0.001). Treatment with ICIs improved survival in patients with both POLE/POLD1 mutated and those with TMB > 18 (p < 0.001). Current smokers have a five-fold increased risk of having POLE mutations than never-smokers. POLE/POLD1 mutation status and TMB > 18 can be a composite biomarker for selecting NSCLC patients with survival benefits to ICI treatment.

Impact of SPARC expression on pembrolizumab treatment response and prognostic role in advanced stage non-small cell lung cancer.

e21042 Background: Secreted protein acidic and cysteine-rich (SPARC) was highly expressed in non-small cell lung cancer (NSCLC) tissue. Studies have indicated the association between SPARC expression and immune-cell infiltration and the prognosis of lung cancer. Despite the optimal first-line treatment approach in advanced NSCLC that lacks a driver mutation includes immunotherapy with or without chemotherapy, a well-defined tool or test for predicting response has yet to be created. We aimed to elucidate the influence of SPARC expression terms of clinicopathology, pembrolizumab response and prognosis in metastatic NSCLC patients. Methods: Thirty-six patients diagnosed with advanced-stage NSCLC without actionable driver mutation and recieved pembrolizumab in the first line setting were included in this study. Programmed death ligand-1(PD-L1) and SPARC expression were assessed by means of PD-L1 IHC 22C3 pharmDx and BenchMark ULTRA assay(Ventana Medical Systems, Tucson, AZ) in paraffin-embedded blocks. The expressions were categorised according to the tumor proportion score. Staining intensity of SPARC was graded according to the following criteria: 1+ (weak), 2+ (moderate), and 3+(strong). Results:The median age was 62 (range 45-81). One patient was female, and four patients did not have a smoking history.Twenty-seven of tumor were adenocarcinoma, and six were squamous cell carcinoma. PDL-1 status was &lt; 1% in 4 (11.4%), 1-49% in 12 (34.3%), and &gt; 50% in 20 (54.3%) patients.There was no significant correlation between SPARC expression and smoking status, histologic type of tumour, T and N status, and liver and bone metastasis. Central nervous system (CNS) metastasis and progression was seen in 8 (57.1%), 2 (12.5%), and 1 (16.7%) and in 6 (16.7%), 0, and 6 (37.5%) patients with SPARC 1+,2+, and 3 +, respectively. Controversially, higher SPARC expression was significantly correlated with lower rates of brain metastasis but higher rates of CNS progression (p = 0.022 and p = 0.011, respectively). While PD-L1 and SPARC expression were not significantly correlated, a trend toward low SPARC expression was seen in patients with PD-L1 &gt; 50%. The objective response rate (ORR) trended to be higher in the SPARC 1+ group (85.7%, 43.8%, and 50.0% in SPARC 1+, 2+ and 3+ group, respectively, p = 0.052). Univariate analysis revealed that SPARC expression was not a significant prognostic factor for both PFS (p = 0.7) and OS (p = 0.07). But, low SPARC expression was a significant predictive factor for the first-line pembrolizumab treatment response (p = 0.04, OR:0.11, 95%CI 0.01-0.92) in NSLC patients. Conclusions: Our study lightened a new area in the literature that SPARC expression might predict the pembrolizumab response and might be a marker for CNS progression in NSLC patients. These results should be explored in further studies to address the potential therapeutic implications of SPARC expression.

A multicenter study of central nervous system (CNS) metastasis in EGFR-mutated advanced non–small-cell lung cancer in Thailand: CNS progression-free survival analysis.

e14002 Background: Central Nervous System (CNS) metastasis is common in patients with advanced stage non-small cell lung cancer (NSCLC), which impacts their survival and quality of life. Nearly Half of NSCLCs in Thailand are EGFR (Epidermal Growth Factor Receptor) mutated NSCLCs. The aim of this study was to define the prevalence of CNS metastasis in EGFR mutated advanced NSCLC in Thai patients and their survival during the year 2013-2019.Now we reported CNS progression free survival data in subgroup with evidence of CNS progression. Methods: We retrospectively conducted a multicenter study of EGFR mutated advanced NSCLC from 9 government hospitals in Thailand from January 2013 to December2019. Demographic data and cancer treatments were recorded with previous reports of overall survival data in all cohorts. Brain imaging was performed upon neurologic signs and symptoms. Treatment of CNS metastasis, CNS progression date and overall survival data were collected. The analysis of CNS progression free survival and overall survival was performed and the effect of Osimertinib was defined. Results: There were 254 patients with advanced EGFR mutated NSCLCs. The prevalence of CNS metastasis was 32.28% (82 patients). There were 25.6% (21) of patients with definite evidence of CNS progression by imaging or clinical. In this group, Brain metastasis at first diagnosis was 61.9% (13 patients). EGFR TKIs was given as first line 42.9% (9 patients), second line 33.3% (7 patients), third line 19% (4 patients). Whereas one patient did not received EGFR TKIs. Most of EGFR TKIs treatment was first generation for 95% (19 patients). Osimertinib was given in 23.8% (5) of patients as second line, third line and fourth line for 2, 1 and 2 patients, respectively. The onset of CNS metastasis before EGFR TKIs was 76.2% when compared to 4.8%, 19% during EGFR TKIs and after EGFR TKIs, respectively. Treatment of brain metastasis was whole brain radiation for 85.7% (18 patients), followed by surgery with whole brain radiation for 14.3% (3 patients). The median CNS progression free survival was 14.00 (9.51,18.48) months. The median CNS progression free survival between no Osimertinib treatment and Osimertinib treatment was 13 (10.38,15.61) months and 21 (17.49,24.5) months, respectively. The median survival was 30.03 (19.6,40.45) months. The median survival between no Osimertinib treatment and Osimertinib treatment was 26.58 (18.96,34.20) months and NR (NR, NR), respectively. Conclusions: The prevalence of CNS progression was 25.6% in patients with EGFR mutated NSCLC in Thailand. Treatment with EGFR TKIs improved CNS progression free survival better than historical data.3rd generation EGFR TKIs Osimertinib in later line prolong clinical benefit of CNS Progression free survival and overall survival better than 1st generation EGFR TKIs alone.