Molecular Profiling: Genomic Guided Therapy for Lung Adenocarcinoma

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Abstract Introduction: Lung cancer accounts for 22% of all cancer fatalities. The overall 5-year survival rate is about 26.6%. Early diagnosis can have a higher survival rate. Unfortunately, lung cancer is often diagnosed at advanced stages when treatment options are limited. The five-year survival rate for non-small cell lung cancer (NSCLC) is 28% and 9% when metastasized. Cancer metastasis consists of a sequential series of events, and mesenchymal-epithelial transition (MET) exon 14 skipping mutations and amplification are recognized as critical events for metastasis of carcinomas. The MET pathway is associated with many malignancies, and in NSCLC is associated with a poor prognosis being found in 3-4% of cases. Most recently Capmatinib, a selective inhibitor of the MET receptor, has shown promise due to its efficacy as monotherapy for MET dysregulated NSCLC. We present a case of a metastatic stage 4A lung adenocarcinoma who achieved stability of his condition after receiving Capmatinib. Case description: Patient is an 83-year-old with past medical history of COPD who presented with acute respiratory failure to the emergency room. Chest CT showed a moderately large pericardial effusion with compression of cardiac chamber and a large irregular solid heterogenous right apical paramediastinal lung mass, with multiple bilateral solid nodules. Patient was stabilized and pericardiocentesis was done which was non-diagnostic for malignancy. After discharge, PET-CT showed a hypermetabolic lung mass indicative of a malignant process, mediastinal lymphadenopathy, bilateral pulmonary nodules and pericardial lesions consistent with metastatic disease. Endobronchial ultrasound bronchoscopy (EBUS) with biopsy of mediastinal station 4R and brushing of right upper lobe were remarkable for lung adenocarcinoma. Immunostains were positive for Napsin A and TTF-1. Immunohistochemistry had more than 90% expression of PD-L1 of tumor cells. Genomic testing showed a MET exon 14 skipping mutation reason why patient was started on Capmatinib achieving 3-year stability of his condition with improvement on size of hypermetabolic lesions. Discussion: This case is an example of a positive outcome utilizing EBUS and genomic profiling for diagnosis and newer treatment modalities such as Capmatinib for NSCLC. With our case we aim to highlight the importance of genetic testing to guide specific therapy in NSCLC as it can significantly improve patient prognosis and morbidity. Additionally, this supports the need of broad molecular profiling before therapy decision making. In our case it is too soon to tell the 5-year prognosis of this patient, but outcome looks promising.

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