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

Journal of Experimental & Clinical Cancer Research

Editta Baldini²  Gabriella Fontanini⁷  Maria Cristina Pennucci⁴  Simona Giovannelli²  Laura Ginocchi⁶  Elisa Sensi⁵  Cristiana Lupi⁵  Aldo Chioni⁸  Giovanna Cirigliano²  Armida D’Incecco³  Antonio Chella¹  Laura Boldrini⁷  Carmelo Tibaldi³  Enrico Vasile⁶  Lorenzo Fornaro²  Virginia Rotella² 

[1] U.O. Pneumologia, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy;U.O. Oncologia Medica, Ospedale San Luca, Lucca, Italy;U.O. Oncologia Medica, Ospedale Civile, Livorno, Italy;U.O. Oncologia Medica, Ospedale di Carrara, Carrara, Italy;U.O. Anatomia Patologica III, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy;U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy;Dipartimento di Patologia Chirurgica, Medica, Molecolare e di Area Critica, Università di Pisa, Pisa, Italy;U.O. Oncologia Medica, Ospedale della Misericordia, Grosseto, Italy

关键词: Tyrosine-kinase inhibitors;    Chemotherapy;    K-Ras;    EGFR;    Lung adenocarcinoma;   

Others  :  1136107
DOI  :  10.1186/s13046-014-0077-6

 received in 2014-09-06, accepted in 2014-09-08,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Rotella et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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