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.

NCOG-03. PREDICTORS OF NEUROLOGIC DEATH IN PATIENTS WITH BRAIN METASTASES

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi152-vi152
Author(s):  
Alexander Reese ◽  
Nayan Lamba ◽  
Paul Catalano ◽  
Daniel Cagney ◽  
Patrick Wen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Her2 Breast Cancer ◽  
Intracranial Disease ◽  
Increased Risk ◽  
Extracranial Disease

Abstract BACKGROUND Neurologic death (ND), defined as intracranial disease progression with accompanying neurologic symptoms in the absence of life-threatening systemic disease, is the most serious consequence of intracranial disease among patients with brain metastases (BMs). Data indicating which factors are predictive of this outcome remain limited, however. Determining which patients are at increased risk of ND will guide improved care and further research aimed at preventing ND. METHODS We identified 1,218 patients with newly diagnosed BMs managed at Brigham and Women’s Hospital from 2008-2015. Demographic and tumor characteristics for patients experiencing ND, non-neurologic death, and who were alive at last follow up were analyzed by univariable and multivariable Fine and Gray competing risks regression to identify predictors of ND, with non-neurologic death serving as a competing risk. RESULTS In multivariable analysis, ND was associated with number of BMs (hazard ratio [HR] 1.01 per 1 metastasis increase, 95% CI 1.01-1.02, p&lt; 0.001) and three primary tumor sites (with non-small cell lung cancer as the reference): melanoma (HR 4.67, 95% CI 3.27-6.68, p&lt; 0.001), small cell lung cancer (HR 2.33, 95% CI 1.47-3.68, p&lt; 0.001), and gastrointestinal cancer (HR 2.21, 95% CI 1.28-3.82, p=0.005). Additionally, among patients with breast primaries, HER2+ tumors displayed increased risk of ND relative to the reference subtype (HR+/HER2-) in univariable analysis (HR 2.41, 95% CI 1.00-5.84, p=0.05). A reduced risk of ND was found in patients with Karnofsky performance status of 90-100 versus 30-80 (HR 0.67, 95% CI 0.48-0.95, p=0.03) and progressive extracranial disease (HR 0.50, 95% CI 0.38-0.67, p&lt; 0.001). CONCLUSION Patients with melanoma, small cell lung cancer, gastrointestinal, and HER2+ breast cancer primaries, in addition to those with greater intracranial versus extracranial disease burdens, are at increased risk of ND. Future research into novel intracranial approaches should focus on these groups of patients.

Evaluation of erlotinib treatment after gefitinib failure in Japanese recurrent non-small cell lung cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19008-e19008
Author(s):  
A. Hata ◽  
S. Nanjo ◽  
R. Kaji ◽  
S. Hujita ◽  
N. Katakami ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Disease Control ◽  
Cell Lung Cancer ◽  
Mutational Analysis ◽  
Small Cell ◽  
Smoking History ◽  
Hematological Toxicity ◽  
Small Cell Lung

e19008 Background: Both gefitinib (G) and erlotinib (E) belong to the family of epidermal growth factor receptor-tyrosine kinase inhibitors that has shown positive results in the treatment of advanced/recurrent non-small-cell lung cancer (NSCLC). Recent studies suggested a distinction in efficacy between G and E. In fact, there is a subgroup of patients who had clinically meaningful benefit with E therapy after G failure, but little is known about the factors that predict disease control or the risk factors that develop toxicity in these patients. Our aim is to evaluate the efficacy and toxicity of E after G failure in the largest scale study to date. Methods: We retrospectively evaluated the efficacy and toxicity of E therapy and analyzed factors that contributed to disease control in patients had experienced G failure. EGFR mutational analysis was performed in evaluable cases. Results: From January 2008 to December 2008, seventy-seven patients were treated with E after G failure in our institutions. Of these 77 patients, 11 had a partial response (PR) and 21 had a stable disease (SD), resulting in a best response rate of 14% and a disease control rate (DCR) of 42%. Thirty of 56 (54%) patients who had benefited from prior G therapy achieved disease control, while only 2 of 20 (10%) patients who had experienced initial progressive disease to G therapy obtained SD (P<0.001) . Twenty-seven of 48 (56%) patients with performance status (PS) 0/1 achieved disease control, but a DCR of PS 2/3/4 patients was only 17% (5 of 29) (P<0.001). EGFR mutation status, smoking history, and gender had little relationship to disease control. In 4 of 11 patients who achieved PR, E was effective for brain metastases. The most common side effects of E therapy were skin rash and diarrhea, as described in previous studies. Notably in approximately 30% of poor PS patients, grade 3 to 4 non-hematological toxicity including severe general malaise and anorexia was observed. Conclusions: E may be effective as a salvage therapy for some Japanese NSCLC patients after G failure, especially in those who had benefited from prior G treatment and/or those who maintain a good PS. Interestingly, E was effective for brain metastases of some patients after G failure. No significant financial relationships to disclose.

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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