Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study

2014 ◽  
Vol 15 (10) ◽  
pp. 1119-1128 ◽  
Author(s):  
Shirish M Gadgeel ◽  
Leena Gandhi ◽  
Gregory J Riely ◽  
Alberto A Chiappori ◽  
Howard L West ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Phase 1 ◽  
Systemic Disease ◽  
Small Cell ◽  
Dose Finding ◽  
Small Cell Lung

scholarly journals Clinical Experience With Crizotinib in Patients With Advanced ALK-Rearranged Non–Small-Cell Lung Cancer and Brain Metastases

2015 ◽  
Vol 33 (17) ◽  
pp. 1881-1888 ◽  
Author(s):  
Daniel B. Costa ◽  
Alice T. Shaw ◽  
Sai-Hong I. Ou ◽  
Benjamin J. Solomon ◽  
Gregory J. Riely ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Disease Control ◽  
Cell Lung Cancer ◽  
Kinase Inhibitor ◽  
Systemic Disease ◽  
Small Cell ◽  
Small Cell Lung ◽  
Intracranial Disease

Purpose Crizotinib is an oral kinase inhibitor approved for the treatment of ALK-rearranged non–small-cell lung cancer (NSCLC). The clinical benefits of crizotinib in patients with brain metastases have not been previously studied. Patients and Methods Patients with advanced ALK-rearranged NSCLC enrolled onto clinical trial PROFILE 1005 or 1007 (randomly assigned to crizotinib) were included in this retrospective analysis. Patients with asymptomatic brain metastases (nontarget or target lesions) were allowed to enroll. Tumor assessments were evaluated every 6 weeks using RECIST (version 1.1). Results At baseline, 31% of patients (275 of 888) had asymptomatic brain metastases; 109 had received no prior and 166 had received prior brain radiotherapy as treatment. Among patients with previously untreated asymptomatic brain metastases, the systemic disease control rate (DCR) at 12 weeks was 63% (95% CI, 54% to 72%), the intracranial DCR was 56% (95% CI, 46% to 66%), and the median intracranial time to progression (TTP) was 7 months (95% CI, 6.7 to 16.4). Among patients with previously treated brain metastases, the systemic DCR was 65% (95% CI, 57% to 72%), the intracranial DCR was 62% (95% CI, 54% to 70%), and the median intracranial TTP was 13.2 months (95% CI, 9.9 to not reached). Patients with systemic disease control were also likely to experience intracranial disease control at 12 weeks (correlation coefficient, 0.7652; P < .001). Among patients without baseline brain metastases who developed progressive disease (n = 253) after initiation of crizotinib, 20% were diagnosed with brain metastases. Conclusion Crizotinib was associated with systemic and intracranial disease control in patients with ALK-rearranged NSCLC who were ALK inhibitor naive and had brain metastases. However, progression of preexisting or development of new intracranial lesions while receiving therapy was a common manifestation of acquired resistance to crizotinib.

Vorinostat and Concurrent Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases: A Phase 1 Dose Escalation Trial

2017 ◽  
Vol 99 (1) ◽  
pp. 16-21 ◽  
Author(s):  
Clara Y.H. Choi ◽  
Heather A. Wakelee ◽  
Joel W. Neal ◽  
Mary C. Pinder-Schenck ◽  
Hsiang-Hsuan Michael Yu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Stereotactic Radiosurgery ◽  
Cell Lung Cancer ◽  
Dose Escalation ◽  
Phase 1 ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals 38P Brain metastases in non-small cell lung cancer in era of molecularly driven therapy

2021 ◽  
Vol 16 (4) ◽  
pp. S714-S715
Author(s):  
S. Rakshit ◽  
R. Bansal ◽  
A. Desai ◽  
K. Leventakos
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Correlation of Clinical Parameters with Intracranial Outcome in Non-Small Cell Lung Cancer Patients with Brain Metastases Treated with Pd-1/Pd-L1 Inhibitors as Monotherapy

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1562
Author(s):  
Konstantinos Rounis ◽  
Marcus Skribek ◽  
Dimitrios Makrakis ◽  
Luigi De Petris ◽  
Sofia Agelaki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Disease Progression ◽  
Cell Lung Cancer ◽  
Response Assessment ◽  
Small Cell ◽  
University Hospital ◽  
Response Analysis ◽  
Small Cell Lung

There is a paucity of biomarkers for the prediction of intracranial (IC) outcome in immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients (pts) with brain metastases (BM). We identified 280 NSCLC pts treated with ICIs at Karolinska University Hospital, Sweden, and University Hospital of Heraklion, Greece. The inclusion criteria for response assessment were brain metastases (BM) prior to ICI administration, radiological evaluation with CT or MRI for IC response assessment, PD-1/PD-L1 inhibitors as monotherapy, and no local central nervous system (CNS) treatment modalities for ≥3 months before ICI initiation. In the IC response analysis, 33 pts were included. Non-primary (BM not present at diagnosis) BM, odds ratio (OR): 13.33 (95% CI: 1.424–124.880, p = 0.023); no previous brain radiation therapy (RT), OR: 5.49 (95% CI: 1.210–25.000, p = 0.027); and age ≥70 years, OR: 6.19 (95% CI: 1.27–30.170, p = 0.024) were associated with increased probability of IC disease progression. Two prognostic groups (immunotherapy (I-O) CNS score) were created based on the abovementioned parameters. The I-O CNS poor prognostic group B exhibited a higher probability for IC disease progression, OR: 27.50 (95% CI: 2.88–262.34, p = 0.004). Age, CNS radiotherapy before the start of ICI treatment, and primary brain metastatic disease can potentially affect the IC outcome of NSCLC pts with BM.

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