RESUMO
The central nervous system (CNS), through carcinomatous meningitis or solid brain metastases, is the most common site of recurrence in non-small cell lung cancers (NSCLC) with activating mutations. Our retrospective study describes the population of patients with CNS metastases of NSCLC harboring activating mutation with targeted therapy (EGFR, ALK, BRAF, HER2) in 4 French regional reference hospitals. 60 patients were analyzed. The proposed treatments were heterogeneous and included combinations of chemotherapy, targeted therapy and radiotherapy±associated with topical treatments. Median overall survival following CNS metastasis in these patients was 15.8 months for meningitis carcinoma and 26 months for brain metastases. In patients with brain metastases, the addition of targeted therapy treatment allows a significant improvement in median progression free survival from 5.9 months to 10.6 months (HR 0.48 CI95 [0.24 to 0.97] P=0.035). These patients seem therefore benefit from systemic therapy and particularly targeted therapy with better survival than usual.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/terapia , Mutação com Ganho de Função , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias do Sistema Nervoso Central/genética , Progressão da Doença , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/genética , Receptor ErbB-2/genética , Estudos RetrospectivosRESUMO
A number of mechanisms that drive oncogenesis have been deciphered over the last 20 years. The main oncogenic factors in the field of thoracic oncology are mutations of EGFR, KRAS, and EML4-ALK translocation, which are most often reported in adenocarcinomas. However, new molecular targets have been highlighted recently including BRAF mutations, HER2 or PI3K, new translocations such as ROS1 or KIF5B-RET. Molecular abnormalities have also been identified in tumors other than adenocarcinoma (squamous and small cell carcinoma). Therapeutic strategies have been designed to inhibit these signaling pathways including monoclonal antibodies and tyrosine kinase inhibitors. Some of these molecules are now approved as therapies, others are currently undergoing testing in clinical trials. We here present a review of novel targeted agents for lung cancer.