RESUMO
The complex therapeutic strategy of non-small cell lung cancer (NSCLC) has changed significantly in recent years. Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation. In oncogenic-addictive metastatic NSCLC, primarily in adenocarcinoma, the range of targeted therapies is expanding, with which the expected overall survival increases significantly, measured in years. By 2021, the FDA and EMA have approved targeted agents to inhibit EGFR activating mutations, T790 M resistance mutation, BRAF V600E mutation, ALK, ROS1, NTRK and RET fusion. In 2022, the range of authorized target therapies was expanded. With therapies that inhibit KRASG12C, EGFR exon 20, HER2 and MET. Until now, there was no registered targeted therapy for the KRAS mutations, which affect 30% of adenocarcinomas. Thus, the greatest expectation surrounded the inhibition of the KRAS G12C mutation, which occurs in â¼15% of NSCLC, mainly in smokers and is characterized by a poor prognosis. Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy. Adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1. In EGFR exon 20 insertion mutation of lung adenocarcinoma, amivantanab was registered for progression after platinum-based chemotherapy. Lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (NGS) expands personalized therapies by identifying guideline-recommended molecular alterations.
Assuntos
Acetonitrilas , Adenocarcinoma de Pulmão , Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Piperazinas , Pirimidinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas/genética , Mutação , Adenocarcinoma/genética , Receptores ErbB/genéticaRESUMO
BACKGROUND: Sotorasib 960 mg once daily is approved to treat KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Sotorasib exhibits non-dose proportional pharmacokinetics and clinical responses at lower doses; therefore, we evaluated the efficacy and safety of sotorasib 960 mg and 240 mg. METHODS: In this phase 2, randomized, open-label study, adults with KRAS G12C-mutated advanced NSCLC received sotorasib 960 mg or 240 mg once daily. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and pharmacokinetics. The study was not powered for formal statistical hypothesis testing. RESULTS: In the 960 mg group (n = 104), ORR was 32.7 % and DCR was 86.5 %. In the 240 mg group (n = 105), ORR was 24.8 % and DCR was 81.9 %. Median PFS was 5.4 months (960 mg) and 5.6 months (240 mg). At a median follow-up of 17.5 months, median OS was 13.0 months (960 mg) and 11.7 months (240 mg). AUC0-24 h and Cmax were 1.3-fold numerically higher with the 960 mg dose. Treatment-emergent adverse events (TEAEs, ≥10 %) for 960 mg and 240 mg doses, respectively, were diarrhea (39.4 %; 31.7 %), nausea (23.1 %; 19.2 %), increased alanine aminotransaminase (14.4 %; 17.3 %), and increased aspartate aminotransferase (13.5 %; 13.5 %). CONCLUSIONS: Patients treated with sotorasib 960 mg once daily had numerically higher ORR and DCR, and longer DOR and OS, than patients treated with 240 mg in this descriptive analysis. TEAEs were manageable with label-directed dose modifications. CLINICAL TRIAL REGISTRATION: NCT03600883.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Mutação , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Masculino , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Idoso , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso de 80 Anos ou mais , Esquema de Medicação , Piridinas/efeitos adversos , Piridinas/administração & dosagem , Piridinas/farmacocinética , Piridinas/uso terapêutico , Intervalo Livre de Progressão , Piperazinas , PirimidinasRESUMO
INTRODUCTION: The correct evaluation of the tracheal wall's structure is necessary for the management of postintubation tracheal stenosis (PTS). Endobronchial ultrasonography (EBUS) is suitable for visualisation of layers of the tracheal wall and the assessment of cartilages' damage. AIM: The authors assessed the usefulness of EBUS in the anatomical characterization of PTS and in the decision making in its therapy. PATIENTS, METHODS: Between March 2002, and September 2003, 22 patients with PTS were examined by bronchoscopy together with EBUS. RESULTS: 13 patients had complex stenosis and from them destruction of tracheal cartilage was demonstrated in 5 patients. Of them bronchoscopic intervention resulted in only short term symptom free period in 3 patients. CONCLUSION: The destruction of tracheal cartilage detected by EBUS might be an indication for an early surgical intervention. According to author's results EBUS can be a useful method in evaluation of PTS.
Assuntos
Brônquios/diagnóstico por imagem , Intubação Intratraqueal/efeitos adversos , Estenose Traqueal/diagnóstico por imagem , Estenose Traqueal/etiologia , Endossonografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Ultrassonografia Doppler em CoresRESUMO
Endobronchial ultrasonography is an imaging method which has been developed during the last decade. It can be performed by applying tools that are used today during conventional bronchofiberscopy. This method is recommended for identifying processes that affect the bronchial wall and the mediastinal lesions next to central airways as well as for localizing peripheral lung lesions. The authors present a compilation of publications and summarize their own experiences based on 44 cases of application of this method.
Assuntos
Brônquios/diagnóstico por imagem , Broncopatias/diagnóstico por imagem , Broncoscopia , Broncoscopia/efeitos adversos , Broncoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Ultrassonografia/efeitos adversos , Ultrassonografia/métodosRESUMO
INTRODUCTION: Benign lung and trachea tumors account for only a small percentage of a bronchologist's and a histopathologist's everyday practice. AIMS: The authors describe the clinicopathological features some of these tumors because they may be confused with malignant conditions. To avoid misdiagnosis of malignancy the knowledge of bronchologic and histologic appearance of these tumors is important. RESULTS: In the past three years 1453 cases were examined and 14 cases of benign tumors were diagnosed, which is 1% of the total number of biopsies and 2.68% of the tumor cases. The diagnoses were: granular cell tumor (Abrokosoff's tumor), neurilemmoma, hemangioma, endobronchial hamartoma, and papillary adenoma. Two of the reported tumors: granular cell tumor and papillary adenoma appeared in the trachea. Tracheal granular cell tumor and bronchial hemangioma were incidental findings beside bronchial carcinoma. CONCLUSION: To our best knowledge this is the fifth reported case of the coexistence of Abrikossoff's tumor with bronchial carcinoma.
Assuntos
Biópsia , Neoplasias Brônquicas/patologia , Neoplasias Pulmonares/patologia , Neoplasias da Traqueia/patologia , Adulto , Idoso , Feminino , Tumor de Células Granulares/patologia , Hamartoma/patologia , Hemangioma/patologia , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Neurilemoma/patologiaRESUMO
Tumor like miscellaneous lung diseases are rare conditions. They can be confused with benign and malignant tumors. We describe the clinicopathological features some of this conditions i.e.: two cases of osteoplastic tracheopathy, one inflammatory tracheal polyp, two cases of tumor mimicking foreign body aspiration, and one case of tracheobronchial amyloidosis.
Assuntos
Amiloidose/diagnóstico , Brônquios , Broncopatias/diagnóstico , Corpos Estranhos/diagnóstico , Pólipos/diagnóstico , Doenças da Traqueia/diagnóstico , Amiloidose/patologia , Broncopatias/patologia , Neoplasias Brônquicas/diagnóstico , Broncoscopia , Diagnóstico Diferencial , Feminino , Corpos Estranhos/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/etiologia , Pólipos/patologia , Doenças da Traqueia/patologia , Neoplasias da Traqueia/diagnósticoRESUMO
INTRODUCTION: Lung cancer is responsible for most cancer deaths in the world. The main reason for the poor prognosis is late diagnosis. Many patients could be successfully treated in early stage. AIMS: The authors performed 369 bronchological examination on 336 patients using autofluorescence bronchoscopy between 1998 and 2003 to detect preinvasive lesions and early forms of lung cancer. METHODS: Storz D-Light autofluorescence system has been used to perform the examinations. RESULTS: In one third of these patients invasive lung cancer developed during follow-up. Combining traditional white light and autofluorescence technique 50% more intraepithelial lesions have been observed and sensitivity has been increased by 69% compared to the lone use of white light bronchoscopy. CONCLUSIONS: Supported by most international studies these results emphasise that autofluorescence bronchoscopy has a major role in the early diagnosis of preinvasive bronchial lesions and may help in the prevention and early therapy of lung cancer.