lunes, 25 de enero de 2016

Examining Treatment Outcomes with Erlotinib in Patients with Advanced Non-Small-Cell Lung Cancer Whose Tumors Harbor Uncommon Epidermal Growth Fact... - PubMed - NCBI

2016 Jan 7. pii: S1556-0864(16)00283-5. doi: 10.1016/j.jtho.2015.12.107. [Epub ahead of print]

Examining Treatment Outcomes with Erlotinib in Patients with Advanced Non-Small-Cell Lung Cancer Whose Tumors Harbor Uncommon Epidermal Growth Factor Receptors Mutations.

Klughammer B1, Brugger W2, Cappuzzo F3, Ciuleanu T4, Mok T5, Reck M6, Tan EH7, Delmar P8, Klingelschmitt G8, Yin AY8, Spleiss O8, Wu L8, Shames DS9.

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Abstract

INTRODUCTION:

Exon 19 deletions and exon 21 L858R mutation of the epidermal growth factor receptor (EGFR) predict activity of EGFR tyrosine kinase inhibitors (TKIs) including erlotinib; however, the ability of less common EGFR mutations to predict efficacy of erlotinib is unclear.

METHODS:

The efficacy of erlotinib in individual patients with rare EGFR mutations from the MERIT, SATURN, TITAN, TRUST, ATLAS, BeTa, and FASTACT-2 trials was analyzed and compared with data from the literature.

RESULTS:

Of the patients tested for biomarkers, the frequency of rare mutations identified here ranged from 1.7% (8/467) in the SATURN study, to 7.4% (27/364) in ATLAS. Some rare mutations were associated with greater clinical benefit with EGFR TKI therapy, or with improved prognosis independent of treatment, while others appeared to have a poorer prognosis. In particular, exon 18 G719 mutations, exon 19 K757R and E746G mutations, the exon 20 S768I mutation, and the exon 21 G836S mutation appeared to confer a good outcome with erlotinib treatment while exon 18 S720I showed a particularly poor outcome. However, due to the small number of patients with each mutation, it is difficult to confirm whether these rare mutations do indeed confer sensitivity or resistance to erlotinib.

CONCLUSIONS:

Erlotinib can have differential efficacy depending on the specific EGFR mutation. More research is needed to create a central database such as the 'My Cancer Genome' database of rare mutations to definitively confirm whether these mutations are activating, resistant, or neutral.