Document Detail

Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer.
MedLine Citation:
PMID:  23154552     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Many patients with oncogene-driven non-small-cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors experience limited sites of disease progression. This study investigated retrospectively the benefits of local ablative therapy (LAT) to central nervous system (CNS) and/or limited systemic disease progression and continuation of crizotinib or erlotinib in patients with metastatic ALK gene rearrangement (ALK+) or EGFR-mutant (EGFR-MT) NSCLC, respectively.
METHODS: Patients with metastatic ALK+ NSCLC treated with crizotinib (n = 38) and EGFR-MT NSCLC treated with erlotinib (n = 27) were identified at a single institution. Initial response to the respective kinase inhibitors, median progression-free survival (PFS1), and site of first progression were recorded. A subset of patients with either nonleptomeningeal CNS and/or four sites or fewer of extra-CNS progression (oligoprogressive disease) suitable for LAT received either radiation or surgery to these sites and continued on the same tyrosine kinase inhibitors. The subsequent median progression-free survival from the time of first progression (PFS2) and pattern of progression were recorded.
RESULTS: Median progression-free survival in ALK+ patients on crizotinib was 9.0 months, and 13.8 months for EGFR-MT patients on erlotinib. Twenty-five of 51 patients (49%) who progressed were deemed suitable for local therapy (15 ALK+, 10 EGFR-MT; 24 with radiotherapy, one with surgery) and continuation of the same targeted therapy. Post-LAT, 19 of 25 patients progressed again, with median PFS2 of 6.2 months.
DISCUSSION: Oncogene-addicted NSCLC with CNS and/or limited systemic disease progression (oligoprogressive disease) on relevant targeted therapies is often suitable for LAT and continuation of the targeted agent, and is associated with more than 6 months of additional disease control.
Andrew J Weickhardt; Benjamin Scheier; Joseph Malachy Burke; Gregory Gan; Xian Lu; Paul A Bunn; Dara L Aisner; Laurie E Gaspar; Brian D Kavanagh; Robert C Doebele; D Ross Camidge
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer     Volume:  7     ISSN:  1556-1380     ISO Abbreviation:  J Thorac Oncol     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-05-07     Revised Date:  2014-08-21    
Medline Journal Info:
Nlm Unique ID:  101274235     Medline TA:  J Thorac Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1807-14     Citation Subset:  IM    
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MeSH Terms
Aged, 80 and over
Brain Neoplasms / mortality,  secondary,  therapy*
Carcinoma, Non-Small-Cell Lung / mortality,  pathology,  therapy*
Catheter Ablation*
Combined Modality Therapy
Disease Progression
Follow-Up Studies
Gene Rearrangement
Lung Neoplasms / mortality,  pathology,  therapy*
Middle Aged
Mutation / genetics
Neoplasm Staging
Protein Kinase Inhibitors / therapeutic use*
Pyrazoles / therapeutic use
Pyridines / therapeutic use
Quinazolines / therapeutic use
Receptor Protein-Tyrosine Kinases / genetics*
Receptor, Epidermal Growth Factor / genetics*
Retrospective Studies
Survival Rate
Young Adult
Grant Support
K12 CA086913/CA/NCI NIH HHS; P50 CA058187/CA/NCI NIH HHS
Reg. No./Substance:
0/Protein Kinase Inhibitors; 0/Pyrazoles; 0/Pyridines; 0/Quinazolines; 53AH36668S/crizotinib; EC protein, human; EC Protein-Tyrosine Kinases; EC, Epidermal Growth Factor; EC lymphoma kinase; J4T82NDH7E/erlotinib

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