Central nervous system metastases of lung adenocarcinoma harboring EGFR-activating mutations: survival results from a multidisciplinary approach, including EGFR-TKIs

ABSTRACT

Objectives: Central nervous system (CNS) metastases are frequent in advanced lung adenocarcinomas harboring EGFR-activating mutations. However, the best treatment approach must be defined. We aimed to evaluate the effectiveness of a multidisciplinary approach for CNS metastases in patients previously untreated with EGFR tyrosine kinase inhibitors (EGFRTKIs). Methods: We performed a retrospective analysis of EGFR-TKI naïve patients with CNS metastases from lung adenocarcinomas harboring EGFR-activating mutations treated in a Brazilian academic cancer center. Data were collected from electronic records. Overall survival (OS) and progression-free survival (PFS) curves were estimated using the Kaplan-Meier method and compared by logrank test. Cox model was used to evaluate prognostic factors. Results: 35 consecutive patients were included. Treatment included an EGFR-TKI (erlotinib or gefitinib) for all patients, whole brain radiation therapy for 26 patients, stereotactic radiosurgery for 2 patients, and surgery for 8 patients. Median PFS and OS were 8.2 and 11.9 months, respectively. In a multivariable analysis, poor Eastern Cooperative Oncology Group performance status (3-4 vs 0-2) was associated with inferior OS (HR 2.86; 95% CI 1.12-6.74; p=0.016), while radiation therapy to treat brain lesions (yes vs no) showed a trend towards improved OS (HR 0.40; 95% CI 0.15-1.06; p=0.066). No difference was seen between upfront and salvage radiation therapy to the brain. Conclusions: A multidisciplinary treatment approach, including an EGFR-TKI, allowed promising outcomes for patients with CNS metastases of lung adenocarcinoma harboring EGFR-activating mutations, but the small number of patients here studied precludes definitive conclusions. Although radiation therapy to treat brain metastases has an important role, the best treatment sequence remains unclear. Currently, the approach must be individualized, considering patient characteristics, tumor biology and healthcare resources availability.

RESUMO

Objetivos: As metástases de sistema nervoso central (SNC) são frequentes em adenocarcinomas pulmonares avançados portadores de mutações ativadoras do EGFR. No entanto, a melhor abordagem de tratamento deve ser definida. Nosso objetivo foi avaliar a eficácia de uma abordagem multidisciplinar para metástases no SNC em pacientes não tratados previamente com inibidores de tirosina quinase do EGFR (EGFR-TKIs). Métodos: Foi realizada uma análise retrospectiva de pacientes virgens de tratamento prévio com EGFR-TKI, com metástases em SNC de adenocarcinomas de pulmão, que albergam mutações ativadoras do EGFR tratadas em um centro acadêmico brasileiro de câncer. Os dados foram coletados em registros eletrônicos. As curvas de sobrevida global (SG) e sobrevida livre de progressão (SLP) foram estimadas pelo método de Kaplan-Meier e comparadas pelo teste de logrank. O modelo de Cox foi utilizado para avaliar fatores prognósticos. Resultados: 35 pacientes consecutivos foram incluídos. O tratamento incluiu um EGFR-TKI (erlotinibe ou gefininibe) para todos os pacientes, radioterapia cerebral total para 26 pacientes, radiocirurgia estereotática para 2 pacientes e cirurgia para 8 pacientes. A SLP e a SG medianas foram 8,2 e 11,9 meses, respectivamente. Em uma análise multivariável, o baixo ECOG-performance status (3-4 vs 0-2) foi associado à SG inferior (HR 2,86; IC 95% 1,12-6,74; p=0,016), enquanto radioterapia para tratar lesões cerebrais (sim vs não) mostrou uma tendência para melhoria da SG (HR 0,40; IC 95% 0,15-1,06; p=0,066). Não foi observada diferença entre radioterapia cerebral no início do tratamento ou de resgate. Conclusões: Uma abordagem de tratamento multidisciplinar, incluindo um EGFR-TKI, permitiu resultados promissores para pacientes com metástases no SNC de adenocarcinoma de pulmão, com mutações ativadoras do EGFR, mas o pequeno número de pacientes aqui estudados exclui conclusões definitivas. Embora a radioterapia para tratar metástases cerebrais tenha um papel importante, a melhor sequência de tratamento permanece incerta. Atualmente, a abordagem deve ser individualizada, considerando as características do paciente, a biologia do tumor e a disponibilidade de recursos em saúde.

Keywords:

Lung neoplasms - Genes - erbB-1 - Central nervous system

Descritores:

Neoplasias pulmonares - Genes - erbB-1 - Sistema nervoso central

Publikationsverlauf

Eingereicht: 14. Juni 2019

Angenommen: 03. April 2020

Artikel online veröffentlicht:
10. Juni 2020

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