Significance of targeted therapy and genetic alterations in EGFR, ALK, or KRAS on survival in patients with non-small cell lung cancer treated with radiotherapy for brain metastases
| Autor: | Jay S. Loeffler, Alice T. Shaw, Lecia V. Sequist, Justin F. Gainor, Henning Willers, Kevin S. Oh, Kimberley S. Mak, Noah C. Choi, Helen A. Shih, Andrzej Niemierko |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty Lung Neoplasms Genotype Afatinib medicine.medical_treatment Clinical Investigations Kaplan-Meier Estimate medicine.disease_cause Targeted therapy Proto-Oncogene Proteins p21(ras) Young Adult Gefitinib hemic and lymphatic diseases Internal medicine Carcinoma Non-Small-Cell Lung Proto-Oncogene Proteins medicine Anaplastic lymphoma kinase Humans Anaplastic Lymphoma Kinase Lung cancer Aged Retrospective Studies Aged 80 and over Crizotinib business.industry Brain Neoplasms Receptor Protein-Tyrosine Kinases Middle Aged medicine.disease respiratory tract diseases ErbB Receptors Survival Rate Treatment Outcome ras Proteins Female Neurology (clinical) Erlotinib KRAS business medicine.drug |
| Zdroj: | Neuro-oncology. 17(2) |
| ISSN: | 1523-5866 |
| Popis: | Non–small cell lung cancer (NSCLC) is increasingly defined by characteristic molecular changes in driver oncogenes. These include activating mutations in the epidermal growth factor receptor (EGFR)1 and Kirsten rat sarcoma viral oncogene homolog (KRAS) genes2 as well as rearrangements in anaplastic lymphoma kinase (ALK).3 An analysis of 800 tumor samples by the Lung Cancer Mutation Consortium identified mutations in 54% of samples, with KRAS mutations (22%), EGFR mutations (17%), and ALK rearrangements (7%) being most common.4 The development of targeted therapy with tyrosine kinase inhibitors (TKIs) has led to improved outcomes for patients with EGFR mutations5,6 or ALK rearrangements.7 Treatment with EGFR TKIs (eg, erlotinib, gefitinib, and afatinib) in patients harboring EGFR mutations significantly improved progression-free survival (PFS) compared with chemotherapy.8–11 Similarly, in a recent phase III trial, ALK-positive patients treated with the ALK TKI crizotinib in the second-line setting experienced improved PFS compared with standard chemotherapy.12 Despite the impact of TKIs in patients with EGFR mutations and ALK rearrangements, there are currently no targeted therapy options for patients with KRAS mutations13 or wild-type (WT) patients without a known driver mutation. Brain metastases are common in NSCLC, occurring in 20%–40% of patients,14,15 and are associated with a poor median survival of 4–8 months.16–18 The primary treatment for brain metastases is cranial radiotherapy, delivered using whole brain radiotherapy (WBRT), involved field radiotherapy (IFRT) to a smaller region of brain,19 or stereotactic radiosurgery (SRS), with or without surgical resection.20,21 Advancements in targeted therapy have led to the use of TKIs as initial therapy for selected patients with EGFR mutations or ALK rearrangements, typically with asymptomatic brain metastases and extracranial disease. However, radiotherapy remains the standard of care for the majority of NSCLC patients, including those with EGFR or ALK genetic alterations and symptomatic brain metastases, progressive brain metastases, or larger disease burden, and all patients without EGFR or ALK genetic alterations.22,23 EGFR TKIs such as erlotinib are known to have some penetration of the blood-brain barrier.24,25 Limited data on the ALK TKI crizotinib have suggested some central nervous system (CNS) activity,26,27 and second-generation ALK TKIs with improved CNS penetration are under development.28 Thus, the use of TKIs for patients with brain metastases and genetic alterations in EGFR or ALK is an area of ongoing investigation. Currently, little is known about the relationship between NSCLC genetic subtype and prognosis after radiotherapy for brain metastases. The purpose of this study was to determine the significance of EGFR, ALK, and KRAS genetic alterations on outcomes after radiotherapy for brain metastases in NSCLC. |
| Databáze: | OpenAIRE |
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