EGFR mutation status in cerebrospinal fluid of NSCLC patients who developed leptomeningeal metastasis after EGFR-TKI treatment.

e18132 Background: EGFR-TKIs are effective against tumor EGFR-mutated NSCLC. Patients with tumor EGFR activating mutation (EGFRmu) (exon 19 deletions or exon 21 L958R) had better survival than those with EGFR wild-type tumors (EGFRwt). Many EGFRmu patients have had disease progression with EGFR-TKI treatment due to central nervous system (CNS) metastases, including meningeal carcinomatosis. The objective of this retrospective study is to compare the causes of death in patients with a known tumor EGFR mutation status who had been treated with EGFR-TKIs. Methods: We retrospectively reviewed the chart records of our advanced NSCLC patients who had received diagnosis, treatment, and supportive and hospice care in our hospital between July 2005 and June 2010. Tumor EGFR mutation status was analyzed using the DNA sequence method. All enrolled patients had a documented cause of death. Results: Ninety-four patients had documented tumor EGFR data, had received EGFR-TKI treatment (either erlotinib or gefitinib), and were with or without previous or salvage systemic chemotherapy. Of them, 36 were EGFRwt and 58 were EGFRmu. Overall survival after starting EGFR-TKI treatment was significantly longer in EGFRmu than in EGFRwt patients (median 68.9 weeks vs. 46.3 weeks, p=0.0058). Twenty-nine patients died of CNS metastases and 65 died of organ(s) failure other than the CNS. Patients who died of CNS metastases had undergone EKGF-TKI treatment significantly longer than those who died of other organ(s) failure (median 32 weeks vs. 7.7 weeks, p=0.0003), with a hazard ratio of 2.308 (95% C.I. 1.452-3.668, p=0.0004). A significantly higher proportion of EGFRmu patients died of CNS metastases (26 of 58, 44.8%) than EGFRwt patients (3 of 36, 8.3%) (p<0.001). Conclusions: EGFRmu NSCLC patients survived longer and had a significantly higher probability of mortality due to CNS metastases than EGFRwt patients. This change in the causes of death due to NSCLC was noted after an era of EGFR-TKI treatment, and will have an important impact on the strategies or management of patient supportive and hospice care.

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Impact of EGFR mutation status on clinical outcome of nintedanib plus docetaxel in patients with previously treated non-small cell lung cancer (NSCLC): Retrospective analysis of Korean nintedanib named-patient usage (NPU) program in NSCLC (KCSG LU14-2).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20638 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20638-e20638

Author(s):

Sook-hee Hong ◽

Ho Jung An ◽

Yun-Gyoo Lee ◽

Hoon-Kyo Kim ◽

Seung-Sei Lee ◽

...

Keyword(s):

Egfr Mutation ◽

Kinase Inhibitor ◽

Objective Response ◽

Egfr Mutations ◽

Clinical Activity ◽

Good Tolerability ◽

Mutation Status ◽

Tki Treatment ◽

Nsclc Patients ◽

Egfr Tki

e20638 Background: Anti-angiogenic agents have been reported to have clinical activity for NSCLC harboring EGFR mutation (mutEGFR) with/without EGFR Tyrosine kinase inhibitor (TKI). We report clinical outcomes of nintedanib plus docetaxel for refractory NSCLC patients conducted by virtue of Korean NPU program. Methods: Patients with NSCLC were eligible if they failed at least one prior systemic treatment. Docetaxel was administered with 75 or 60mg/m2 on D1 or 37.5mg/m2 on D1, D8 every 3 weeks plus nintedanib 200mg orally twice daily. Nintedanib treatment was continued until disease progression or unacceptable toxicity after 4-6 cycles of combination therapy. Results: Of 62 patients enrolled, 23 patients had activating EGFR mutations (14 in exon19 deletion, 7 exon21 L858R/L861Q, 1 exon20 duplication, and 1 in both exon19 deletion and exon20 T790M) and progressed during prior EGFR-TKI treatment. Of 23 patients, 22 had progressed during or after platinum doublet chemotherapy. Only for 2 patients, EGFR mutation status was unknown. The majority of patients were heavily pretreated, with 43.7% received nintedanib plus docetaxel as ≥ 4th line therapy. 4 patients had prior bevacizumab treatment. Objective response rate (ORR) was 22.9%. Median PFS and OS were 3.9 months (95% CI 3.1-4.6) and 9.5 months (95% CI 5.3-13.7), respectively. Depending on EGFR mutation status, ORR in mutEGFR group was higher than wtEGFR group (30.4% vs 20%, p= 0.50) and median PFS in mutEGFR group was significantly longer than wtEGFR group (6.1 vs 3.3 months, p= 0.008). No treatment related death was reported. Common grade 3/4 adverse events were neutropenia (58.3%) and reversible elevated liver enzyme (18.8%). Conclusions: Taken together, nintedanib plus docetaxel showed meaningful clinical activity with good tolerability for refractory NSCLC patients. Our data suggest that this combination may be a recommendable regimen for EGFR-TKI-resistant mutEGFR NSCLC.

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141PD A prospective study of molecular testing status in the EGFR mutation positive NSCLC patients with disease progression during EGFR TKI treatment (REMEDY study)

Journal of Thoracic Oncology ◽

10.1016/s1556-0864(18)30415-5 ◽

2018 ◽

Vol 13 (4) ◽

pp. S82-S83 ◽

Cited By ~ 1

Author(s):

K. Kanai ◽

N. Yamamoto ◽

N. Nogami ◽

S. Atagi ◽

H. Saka ◽

...

Keyword(s):

Prospective Study ◽

Disease Progression ◽

Egfr Mutation ◽

Molecular Testing ◽

Tki Treatment ◽

A Prospective Study ◽

Nsclc Patients ◽

Egfr Tki

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ctDNA detection of EGFR mutations in NSCLC patients using TargetSelector.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e23037 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e23037-e23037

Author(s):

Frans Beerkens ◽

Chul Kim ◽

Syed P. Hasan ◽

Deepa Suresh Subramaniam ◽

Stephen V. Liu ◽

...

Keyword(s):

Liquid Biopsy ◽

Egfr Mutation ◽

Stage Iv ◽

Detection Sensitivity ◽

Egfr Mutations ◽

Blood Draw ◽

Mutation Status ◽

Activating Egfr Mutation ◽

Nsclc Patients ◽

Egfr Tki

e23037 Background: EGFR mutations are the most frequent targetable genomic alterations in non-small cell lung cancer (NSCLC) patients (pts). While tissue biopsy remains the standard for assessing of EGFR mutation status, it is invasive and not always feasible. Liquid biopsy is a minimally invasive alternative. Biocept’s proprietary TargetSelector system evaluates circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) in blood. We aimed to clinically validate the accuracy of EGFR-specific TargetSelector in NSCLC pts. Methods: At three time points (T0: baseline before TKI, T1: during EGFR-TKI therapy, T2: after progression), blood samples were collected in Biocept OncoCEE BCT validated to preserve DNA up to 8 days. These samples were interrogated for three EGFR mutations: exon 19 deletions (Del 19), L858R, and T790M. The objectives are to assess detection sensitivity of liquid biopsy using EGFR mutation status vs the tissue as gold standard and to evaluate whether the detection sensitivity changes with EGFR-TKI therapy. Results: A total of 53 study pts were enrolled (male, 21; female, 32). The mean age was 70.6 (range: 46 – 90). Most pts had stage IV disease (43, 81.1%) and lung adenocarcinoma (48, 90.6%). 26 (49.1%) pts had EGFR mutations in tumor tissue: Del 19, 13; L858R, 8; T790M, 6; other, 8. Detection sensitivity for sensitizing EGFR mutations (Del 19 and L858R) at T0, T1, and T2 was 60.0% (6/10), 33.3% (5/15), and 33.3% (1/3), respectively. There was no statistical difference in CTC counts between activating EGFR mutation-positive and -negative pts (mean CTC count: 10.5 vs 20.1; p = 0.11 by two-sided t-test). Detection sensitivity for T790M was 33.3% (2/6) and 5 of 6 pts were receiving T790M directed therapy (3, rociletinib; 2, osimertinib) at the time of blood draw. Two pts – one patient before initiation of EGFR-TKI and the other during treatment with erlotinib – were found to have T790M mutations only in blood and not in tissue. Conclusions: Activating EGFR mutation detection may decrease during the course of TKI therapy, possibly due to treatment response. Further research with an expanded sample size and serial collections are needed to evaluate this finding, and to investigate possible implications of the presence of T790M only in blood.

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EGFR mutation status in plasma and tumor tissues in non-small cell lung cancer serves as a predictor of response to EGFR-TKI treatment

Cancer Biology & Therapy ◽

10.1080/15384047.2016.1139238 ◽

2016 ◽

Vol 17 (3) ◽

pp. 320-327 ◽

Cited By ~ 12

Author(s):

Dan Que ◽

He Xiao ◽

Baojian Zhao ◽

Xu Zhang ◽

Qiushi Wang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Egfr Mutation ◽

Small Cell ◽

Small Cell Lung ◽

Mutation Status ◽

Tumor Tissues ◽

Tki Treatment ◽

Egfr Tki

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An observational retrospective study to evaluate the incidence of acquired EGFR T790M resistance in NSCLC patients with EGFR mutation following progression after at least one prior EGFR TKI treatment in Taiwan: ARISE study

Annals of Oncology ◽

10.1093/annonc/mdz437.024 ◽

2019 ◽

Vol 30 ◽

pp. ix168

Author(s):

S.-G. Wu ◽

C.-L. Chiang ◽

C.-Y. Liu ◽

C.-C. Wang ◽

P.-L. Su ◽

...

Keyword(s):

Retrospective Study ◽

Egfr Mutation ◽

Tki Treatment ◽

Nsclc Patients ◽

Egfr Tki ◽

Egfr T790m

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Emergence of RET rearrangement co-existing with activated EGFR mutation in EGFR -mutated NSCLC patients who had progressed on first- or second-generation EGFR TKI

Lung Cancer ◽

10.1016/j.lungcan.2015.06.021 ◽

2015 ◽

Vol 89 (3) ◽

pp. 357-359 ◽

Cited By ~ 45

Author(s):

Samuel J. Klempner ◽

Lyudmila A. Bazhenova ◽

Fadi S. Braiteh ◽

Petros G. Nikolinakos ◽

Kyle Gowen ◽

...

Keyword(s):

Second Generation ◽

Egfr Mutation ◽

Ret Rearrangement ◽

Nsclc Patients ◽

Egfr Mutated ◽

Egfr Tki

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Efficacy and Acquired Resistance of EGFR-TKI Combined with Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Non-Small Cell Lung Cancer in a Real-world Setting

10.21203/rs.3.rs-121107/v1 ◽

2020 ◽

Author(s):

Qianqian Wang ◽

Wen Gao ◽

Fangyan Gao ◽

Shidai Jin ◽

Tianyu Qu ◽

...

Keyword(s):

Egfr Mutation ◽

Advanced Nsclc ◽

Acquired Resistance ◽

Small Cell ◽

Combination Group ◽

Monotherapy Group ◽

Small Cell Lung ◽

T790m Mutation ◽

Nsclc Patients ◽

Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

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