EGFR and K-Ras mutations in women with lung adenocarcinoma: implications for treatment strategy definition View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

Virginia Rotella, Lorenzo Fornaro, Enrico Vasile, Carmelo Tibaldi, Laura Boldrini, Antonio Chella, Armida D'Incecco, Giovanna Cirigliano, Aldo Chioni, Cristiana Lupi, Elisa Sensi, Laura Ginocchi, Simona Giovannelli, Maria Cristina Pennucci, Gabriella Fontanini, Editta Baldini

ABSTRACT

BACKGROUND: We aimed at investigating the outcomes of female patients with stage IIIB-IV adenocarcinoma of the lung according to EGFR and K-Ras mutational status. METHODS: One hundred and three consecutive female patients genotyped at a single Italian Institution were analyzed. Patients were planned to receive first-line platinum-based chemotherapy (CT) and a salvage treatment with anti-EGFR tyrosine-kinase inhibitors (TKIs) was proposed irrespective of tumor mutational status. EGFR (exons 18-21) and K-Ras (exon 2, codons 12-13) mutations were evaluated by real-time PCR and pyrosequencing. The association of mutational status with clinical variables and treatment benefit was investigated by chi-square test and log-rank test. RESULTS: EGFR and K-Ras mutations were found in 31 (30%) and 13 (15%) cases, respectively. Sixty-six patients received platinum CT: no correlation was observed between EGFR or K-Ras mutational status and response rate (RR) (p > 0.05). However, patients treated with first-line CT harboring EGFR activating mutations experienced a significantly reduced progression-free survival (PFS) in comparison with wild-type ones (4.4 vs. 6.4 months, respectively; HR 0.597, 95% CI 0.287-0.975; p = 0.048). Thirty-nine patients received salvage treatment with erlotinib: EGFR activating mutations were significantly correlated with RR (60% vs. 12.5%; p = 0.004) and PFS (11.4 vs. 4.5 months; HR 0.491, 95% CI 0.216-0.936; p = 0.044). Responses to erlotinib were not reported among women with K-Ras mutant tumors, while 50% of those with wild-type K-Ras achieved an objective remission (p = 0.296). Median PFS (3.5 vs. 8.8 months; HR 0.284, 95% CI 0.015-0.510; p = 0.010) and OS (3.9 vs. 19.8 months; HR 0.158, 95% CI 0.001-0.075; p < 0.001) were significantly shorter among K-Ras mutant patients treated with TKI. CONCLUSIONS: In our population of Caucasian women with advanced lung adenocarcinoma we observed that the presence of EGFR activating mutations correlates with a significant reduction in the benefit from first-line platinum-based CT, emphasizing the importance of an upfront use of anti-EGFR TKIs in this patient subset. K-Ras mutations seem to correlate with a detrimental effect from anti-EGFR TKI, but this finding deserves further investigation. More... »

PAGES

77

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13046-014-0077-6

DOI

http://dx.doi.org/10.1186/s13046-014-0077-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052399524

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25300933


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