scholarly journals Tyrosine Kinase Inhibitors as a Treatment of Symptomatic CNS Metastases in Oncogene-Driven NSCLC

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Omer Gal ◽  
Elizabeth Dudnik ◽  
Ofer Rotem ◽  
Inbar Finkel ◽  
Idit Peretz ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Case Series ◽  
Clinicopathological Characteristics ◽  
Leptomeningeal Disease ◽  
Next Generation ◽  
Cns Metastases ◽  
Valuable Treatment ◽  
Nsclc Patients

Central nervous system (CNS) metastases occur frequently in oncogene-driven non-small cell lung cancer (NSCLC). Standard treatment approaches can potentially delay systemic treatment (surgical intervention) or result in neurocognitive impairment (radiotherapy). Recently, next-generation tyrosine kinase inhibitors (TKIs) have demonstrated remarkable intracranial activity. However, most clinical trials did not enroll patients suffering neurological symptoms. Our study aimed to assess the CNS activity of targeted therapies in this patient population. We present a case series of nine NSCLC patients with either EGFR mutation or ALK rearrangement and symptomatic CNS metastases that were treated with TKIs. Clinicopathological characteristics, treatment, and outcomes were analyzed. Most patients presented with symptomatic CNS metastases at time of metastatic disease presentation (6/9). Additionally, the majority of patients had leptomeningeal disease (6/9) and multiple parenchymal metastases. Patients presented with a variety of CNS symptoms with the most common being nausea, vomiting, headache, and confusion. Most patients (6/9) responded rapidly both clinically and radiographically to the targeted treatment, with a marked correlation between systemic and intracranial radiographic response. In conclusion, upfront use of next-generation TKIs in patients with oncogene-driven NSCLC with symptomatic CNS metastases is associated with reasonable intracranial activity and represents a valuable treatment option.

scholarly journals BIOM-01. TYROSINE KINASE INHIBITORS AS A TREATMENT OF SYMPTOMATIC CNS METASTASES IN ONCOGENE-DRIVEN NSCLC

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii1-ii1
Author(s):  
Alexandra Benouaich-Amiel ◽  
Omer Gal ◽  
Elizabeth Dudnik ◽  
Ofer Rotem ◽  
Inbar Finket ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Case Series ◽  
Clinicopathological Characteristics ◽  
Next Generation ◽  
Cns Metastases ◽  
Alk Rearrangement ◽  
Whole Brain Radiation

Abstract BACKGROUND Central nervous system (CNS) metastases occur frequently in oncogene-driven non-small cell lung cancer (NSCLC). Standard treatment (i.e surgery, whole brain radiation therapy or stereotactic radiosurgery) approaches can potentially delay systemic treatment and/or result in neurocognitive impairment. Recently, next generation tyrosine kinase inhibitors (TKIs) have demonstrated a remarkable intracranial activity. However, most clinical trials did not enroll patients with neurological symptoms. Our study aims to assess the CNS activity of targeted therapy in this patient population. METHOD We present a case series of nine NSCLC patients with either EGFR mutation of ALK rearrangement and symptomatic CNS metastases that were treated with TKIs, without radiation therapy or surgery. Clinicopathological characteristics, treatment and outcome were analyzed. RESULTS Most patients presented with symptomatic CNS metastases at time of metastatic disease presentation (6/9 patients). Additionally, the majority of patients had leptomingeal disease (6/9 patients) and multiple parenchymal metastases. Patients presented with a variety of CNS symptoms with the most common being nausea, vomiting, headache and confusion. Five patients were treated with Osimertinib. One patient with ALK rearrangement was treated with Lorlatinib. The remaining 3 patients received either Gefitinib or Afatinib. Most patients (6/9 patients) responded rapidly both clinically and radiographically to the targeted treatment, with a marked correlation between systemic and intracranial radiographic response. CONCLUSION Upfront use of next generation TKIs in patients with oncogene-driver NSCLC with symptomatic CNS metastases is associated with reasonable intracranial activity and represents a valuable treatment option.

scholarly journals Radiographic appearance of leptomeningeal disease in patients with EGFR-mutated non-small-cell lung carcinoma treated with tyrosine kinase inhibitors: a case series

CNS Oncology ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. CNS42 ◽  
Author(s):  
Ugur Sener ◽  
Nassim Matin ◽  
Helena Yu ◽  
Andrew Lin ◽  
T Jonathan Yang ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Case Series ◽  
Small Cell ◽  
Leptomeningeal Disease ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Egfr Mutant ◽  
Egfr Mutated

EGFR is frequently mutated in non-small-cell lung carcinomas (NSCLCs). Clinically available tyrosine kinase inhibitors (TKIs) are effective in treating EGFR-mutant NSCLC. In this case series, we present five patients with TKI-treated EGFR-mutated NSCLC who developed leptomeningeal disease (LMD) lacking characteristic imaging findings. All five patients received TKIs prior to development of cytology-confirmed LMD. Clinical signs of LMD preceded radiographic evidence by 2–12 months. T790M, the most common resistance mutation to first-generation EGFR inhibitors, was identified in four cases. These cases illustrate that in patients with EGFR-mutant NSCLC, TKIs may effectively control LMD, creating a lag between onset of symptoms and observation of radiographic findings.

DDRE-02. PATIENTS WITH LEPTOMENINGEAL METASTASES FROM NSCLC BENEFITED FROM INTRATHECAL PEMETREXED AFTER FAILURE TO TYROSINE KINASE INHIBITORS: TWO CASE REPORTS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi74-vi74
Author(s):  
Minting Ye ◽  
Lei Wen ◽  
Jiangfen Zhou ◽  
Linbo Cai
Keyword(s):  
Quality Of Life ◽  
Overall Survival ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Intrathecal Injection ◽  
Leptomeningeal Metastases ◽  
Adenocarcinoma Of The Lung ◽  
Nsclc Patients

Abstract BACKGROUND The incidence of leptomeningeal metastasis (LM) is 3%-5% in NSCLC patients; the incidence is even higher in patients with EGFR mutations or ALK gene rearrangement. The prognosis of NSCLC patients with LM is poor with an overall survival (OS) of 3 months with contemporary treatment. METHODS Here we report two cases of patients with leptomeningeal metastases from NSCLC who benefited from intrathecal pemetrexed after failure to tyrosine kinase inhibitors(TKIs). RESULTS A 53-year-old woman, diagnosed with adenocarcinoma of the lung with ALK rearrangement, suffered form right limb weakness, dysphagia after multi-line targeted therapy and radiotherapy for brain metastases. Evaluation revealed a rapidly progressing right brainstem mass and diffuse leptomeningeal enhanced. And cytological examination of CSF showed neoplastic cells, which definitely diagnosed as LM. After first intrathecal injection of 30mg pemetrexed every three weeks, the patient's symptoms improved. There were no significant treatment side effects and the quality of life was not affected during the five subsequent treatments. Another patient was a 32-year-old man, diagnosed with adenocarcinoma of the lung with EGFR E24-RAD51E4 fusion mutation with KPS score 30. LM was confirmed after multiline therapy. He suffered form blurred vision and drooping eyelid. Similarly, after first intrathecal injection of 20mg pemetrexed every week, the patient's symptoms improved and KPS score increased gradually. And level II leukopenia was detected during subsequent treatments. Combined with intrathecal pemetrexed progression-free survival (PFS) were 3 months in two NSCLC patients with LM harboring ALK/EGFR mutation . And the quality of life of patients were effectively increased. CONCLUSION Combination therapy third generation EGFR/ALK agents with intrathecal chemotherapy might be benefited in overall survival.

scholarly journals Invasive aspergillosis complicating treatment with tyrosine kinase inhibitors

2019 ◽  
Vol 12 (1) ◽  
pp. e226121 ◽  
Author(s):  
Tajwar Nasir ◽  
Claudia Lee ◽  
Alexandra SC Lawrence ◽  
Jeremy S Brown
Keyword(s):  
Tyrosine Kinase ◽  
Invasive Aspergillosis ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Case Series ◽  
High Dose ◽  
Effective Management ◽  
Traditional Risk Factors ◽  
Tki Treatment ◽  
Systemic Corticosteroid Therapy

We describe three cases of pulmonary aspergillosis (PA) in three patients without traditional risk factors for invasive aspergillosis infection, such as prolonged neutropenia or high dose systemic corticosteroid therapy. All three patients developed PA while taking tyrosine kinase inhibitors (TKI) and sustained greater clinical improvement once TKI were withdrawn. Our case series supports the theory TKI treatment can increase susceptibility to PA without causing neutropenia. Recognition that TKI treatment may predispose to invasive aspergillosis will allow for rapid recognition of affected patients and more effective management of future cases.

Preliminary analysis of biomarkers in plasma by SELDI to predict the response to EGFR tyrosine kinase inhibitors (TKIs) in NSCLC patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7189-7189
Author(s):  
L. Zhang ◽  
L. Ning ◽  
X. Zhang ◽  
Z. Q. Pan ◽  
X. Wang ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Training Set ◽  
Egfr Tyrosine Kinase ◽  
Egfr Tyrosine Kinase Inhibitors ◽  
Nsclc Patients ◽  
Egfr Tkis ◽  
Tof Ms ◽  
Testing Set

7189 Background: The identification of NSCLC patients who are most likely to respond to EGFR tyrosine kinase inhibitors (TKIs) have been investigated intensively. Although screenings for EGFR mutation and gene copy number are promising, these tests are not yet widely available. New predictor markers are urgently needed. The objective of this study was to identify proteomic markers in plasma to predict benefits for patients treated with EGFR TKIs. Methods: Proteomic spectra derived from plasma samples from EGFR TKIs-responsive patients and non-responsive patients were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). These proteomic spectra (WCX2 chips, Ciphergen Biosystems, Inc.) were then analyzed by comparing protein profiles in different response groups (PR Vs PD, training set). Another group of patients treaded with EGFR TKIs will be serving as testing set to validate the result of training set. Results: Totally, fifty-four advanced NSCLC patients were included in this study. All patients were treated with single agent of gefitinib or erlotinib. Twenty-nine patients were included in training set of this study. All were suitable for response evaluation. Ten patients (34.5%) were PR, 8 (27.6%) were SD, and 11 (37.9%) were progressive disease (PD). Total six significant protein peaks were significant (m/z 4288, 4595, 9191, 9349, 9397, and 9563) between PR group and PD group (table). Another twenty-five patients were included for testing set. Analyzing of testing set is still going on. Table shows PR and PD patients’ plasma comparison on WCX2 chips. Conclusions: This preliminary “training” set of spectra that uses SELDI-TOF MS technology found that six protein peaks seemed to be very important biomarkers to predict the response to gefitinib. Prospective tests to confirm these proteins and peptides will be present at this meeting. These results are promising for identifying new biomarkers of EGFR TKIs with SELDI. [Table: see text] No significant financial relationships to disclose.

Efficacy of tyrosine kinase inhibitors (TKIs) based on the ALK resistance mutations on amplicon-based liquid biopsy in ALK positive non-small cell lung cancer (NSCLC) patients (pts).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3055-3055
Author(s):  
Laura Mezquita ◽  
Aurélie Swalduz ◽  
Cecile Jovelet ◽  
Sandra Ortiz-Cuaran ◽  
David Planchard ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Next Generation ◽  
Resistance Mutations ◽  
Durable Response ◽  
Free Survival ◽  
Alk Positive ◽  
Nsclc Patients

3055 Background: Acquired ALK resistance mutations (mut.) are the main mechanism of tyrosine kinase inhibitor (TKI) resistance (30-50%). While next-generation TKIs are more active on mut. than earlier TKIs, compound ALK resistance are associated with failure to next-generation TKIs. We evaluated the clinical utility of detecting ALK resistance mutations in blood to predict TKI efficacy. Methods: ALK positive advanced NSCLC pts were prospectively enrolled between Oct. 2015 and Aug. 2018 in 8 French institutions. Prospective samples were collected; ctDNA was analyzed by amplicon-based Inivata InVisionFirst-Lung. Results: A total of 101 pts with advanced ALK positive NSCLC were enrolled and 328 samples collected. In samples collected at TKI failure (N=74), we detected 9 single and 7 complex (≥2) ALK resistance mut. (22%), associated with EML4-ALK variant 3 (38%) vs. variant 2 (13%) vs. variant 1 (none); 30% had other somatic mut. (mainly TP53 and KRAS, PI3KCA, MET, etc.). No mutations were detected in 48% of samples (ctDNA neg). ALK mut. were more frequent after 2nd/3rd generation TKI (43% post-lorlatinib (7), 29% post-2nd gen. (31), 11% post-crizotinib (36)). ALKG1202R was the most common, as single (n=3) or complex mut. (n=4). The median overall survival (mOS) was 100.4 mo. (95% CI 41.9-158.9) and the median progression free-survival (mPFS) to subsequent line was 2.8 mo. (0.7-4.9). Patients with ctDNA neg had mOS of 105 mo. (39.3-172.1) vs. 58.5 mo. (33.1-84.0) if ≥1 ALK mut. vs. 44.1 mo. (20.0-68.2) if others ( P=0.001). Pts with the complex ALK mut. had worse OS compared to singles ALK mut. (mOS 26.9 mo. vs. 58.5 mo., P=0.001); ALK complex mut. were associated with poor efficacy to subsequent therapy (PFS <3 mo. in 57%; no cases with PFS >6 mo.) vs. single mut., with longer PFS (PFS >6 mo. in 56%). Detectable ALKG1202R mut. were associated with shorter median OS (58.3 mo.; 7.9-109.1) vs. overall population; 86% of cases developed rapid PD (PFS <3mo.) to subsequent therapy with only one durable response to lorlatinib (PFS >6mo.). Conclusions: The absence of ctDNA mutations at TKI failure was associated with prolonged OS, whereas complex ALK mutations at TKI failure may predict resistance to subsequent therapy. Larger and specifically designed studies should be performed to validate these findings.

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