Prognostic impact of EGFR and KRAS mutations in lung cancer survival during pre-tki era: the real scenario at a cancer public center of reference in Brazil

ABSTRACT

Objective: To evaluate the genetic tests is fundamental for the adequate treatment of non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKI). Given that access to this evaluation is still limited for those who depend on the Brazilian Public Health System, it seems important to provide regulatory agencies with epidemiological and prognostic information to guide future health policies and guidelines in Brazil. This work aims to characterize EGFR and KRAS mutations in NSCLC and associating them with patients demographic and tumor clinical-pathologic features. Methods: From 2004 to 2017, 237 metastatic NSCLC patients treated at Erasto Gäertner Cancer Hospital were included in this study. Electronic medical records were retrospectively reviewed and the mutational status EGFR and KRAS were defined. Results: We detected EGFR mutation in 20 samples (15.7%), and KRAS mutation in 26 samples (21.5%). The majority of EGFR mutations was detected within the exon 19 (n=9, 45.0%), and for KRAS G12V (n=8, 30.8%) and G12C (n=8, 30.8%) were the hotspots. The median overall survival was 11 months. We did not detect any statistical differences in survival rates between mutated and wild-type tumors neither for EGFR (p=0.898) nor for KRAS (p=0.458). Only two patients had access to TKI and were considered outliers with the best survival rates. Conclusion: We described important information about NSCLC biological behavior in a population treated in a reference public cancer center in South Brazil. Studies like this highlight the magnitude that TKI treatment could have in the overall survival of patients with NSCLC after being introduced into the SUS. Future studies that address the economic impact of this issue are also needed. Here we also make a comparison of our results with other regions of Brazil that have different genetic backgrounds to evaluate the impact of targeted therapies.

RESUMO

Objetivo: Avaliar os testes genéticos é fundamental para o tratamento adequado do câncer de pulmão de não pequenas células (CPNPC) com inibidores da tirosina quinasse (TKI). Dado que o acesso a esta avaliação ainda é limitado para aqueles que dependem do Sistema de Saúde Pública do Brasil, parece importante proporcionar às agências reguladoras informação epidemiológica y de prognóstico para guiar as políticas e diretrizes de saúde futuras no Brasil. Este trabalho tem como objetivo caracterizar as mutações de EGFR y KRAS em CPNPC y associá-las com as características demográficas y tumorais clínico-patológicas dos pacientes. Métodos: de 2004 a 2017, se incluíram neste estudo 237 pacientes com CPNPC metastático tratados no Hospital de Câncer Erasto Gäertner. Os prontuários electrónicos foram revisados retrospectivamente y se definiram os estados mutacionais EGFR y KRAS. Resultados: Detectamos a mutação EGFR em 20 amostras (15.7%) e a mutação KRAS em 26 muestras (21.5%). A maioria das mutações de EGFR foram detectadas no exão 19 (n = 9, 45.0%), y para KRAS G12V (n = 8, 30.8%) y G12C (n = 8, 30.8%) foram os pontos críticos. A mediana de supervivência global foi de 11 meses. Não detectamos nenhuma diferencia estadística nas taxas de supervivência entre tumores mutados e do tipo selvagem nem para EGFR (p = 0,898) nem para KRAS (p = 0,458). Só dois pacientes tiveram acesso à TKI y se consideraram valores atípicos com as melhores taxas de supervivência. Conclusão: descrevemos informação importante sobre o comportamento biológico do CPNPC numa população tratada em um centro público de referência de câncer no sul do Brasil. Estudos como este destacam a importância que o tratamento com TKI poderia ter na supervivência general dos pacientes com CPNPC depois da sua introdução no SUS. Também se necessitam estudos futuros que abordem o impacto económico deste problema. Aqui também realizamos uma comparação dos nossos resultados com outras regiões do Brasil que têm diferentes antecedentes genéticos para avaliar o impacto das terapias dirigidas.

Keywords:

Lung Neoplasms - Genes - erbB-1 - Kirsten murine sarcoma virus - Public Health - Brazil.

Descritores:

Neoplasias Pulmonares - Genes - erbB-1 - Vírus do sarcoma murino de Kirsten - Saúde pública - Brasil.

AUTHOR'S CONTRIBUTION

Thais Abreu Almeida: Collection and assembly of data, Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing, Provision of study materials or patient.

Jeanine Marie Nardin: Collection and assembly of data, Data analysis and interpretation, Manuscript writing, Provision of study materials or patient.

Amanda Jurgensen: Collection and assembly of data, Provision of study materials or patient.

Janaina Takahashi: Collection and assembly of data, Provision of study materials or patient.

Juliana Jung: Provision of study materials or patient.

Graziele Losso: Collection and assembly of data, Data analysis and interpretation, Manuscript writing, Provision of study materials or patient.

José C. Casali-da-Rocha: Conception and design, Data analysis and interpretation, Final approval of manuscript, Manuscript writing.

Publication History

Received: 29 October 2018

Accepted: 20 February 2019

Article published online:
15 April 2019

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