osimertinib and Carcinoma--Adenosquamous

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition; sterile vegetations attach to heart valves. NBTE is typically found in patients with malignancies or autoimmune disorders. Although surgical interventions are sometimes performed, the appropriate indication and timing are still unclear. Here, we describe a 72-year-old woman diagnosed with adenosquamous carcinoma of the lung. She was initially diagnosed as pT2aN0M0 and underwent RUL lobectomy. After nine months, lung cancer recurred, and she underwent treatment with cytotoxic chemotherapy. However, images showed progression after only one month. Rebiopsy revealed she had comutation of de novo EGFR L858R and T790M. Treatment was changed to gefitinib. After one month, she experienced loss of consciousness. Brain magnetic resonance imaging (MRI) showed multiple lesions resembling infarctions or metastases. Chest computed tomography (CT) revealed progression. Osimertinib was prescribed and she underwent echocardiography to rule out the possibility of a cardiogenic embolism. Surprisingly, severe mitral regurgitation and a massive vegetation on the mitral valve were found. Cardiologists recommended surgery due to the severity of the embolic event and valve dysfunction, but it was decided to continue antibiotics, osimertinib, and anticoagulants instead of surgery due to the patient's poor general condition and the possibility of NBTE. Six weeks later, the patient's condition markedly improved and echocardiography revealed a marked reduction in vegetation size. Clinicians should be aware that targeted therapy can be effective in treating severe cancer complications, such as NBTE, as evidenced by the successful treatment of lung cancer with osimertinib. This option should be considered, particularly for elderly lung cancer patients, before resorting to surgery as a first-line treatment for NBTE.

Topics: Aged; Carcinoma, Adenosquamous; ErbB Receptors; Female; Humans; Lung; Lung Neoplasms; Mutation; Neoplasm Recurrence, Local; Protein Kinase Inhibitors

The identification of epidermal growth factor receptor (EGFR) mutations represents a milestone in the treatment of advanced non-small cell lung cancer. Patients with lung adenosquamous carcinomas (ASCs) rarely present with germline EGFR T790M mutation. The optimal treatment for cancers with germline EGFR T790M mutation (especially ASC) is not clear.. Using next-generation sequencing, we tested 450 cancer-related genes in a 27-year-old patient's lung adenosquamous carcinoma and matched blood samples. Germline mutations in samples from the patient's available relatives were identified by Sanger sequencing.. We identified germline EGFR T790M mutation in the patient's lung adenosquamous carcinoma. He was treated with osimertinib and achieved complete response for more than 30 months, without significant drug-related adverse events. Genetic testing showed that germline EGFR T790M mutation might be a characteristic of inherited lung cancer.. Osimertinib can be a treatment option for patients with lung ASC harboring germline EGFR T790M mutation.. A patient with adenosquamous carcinoma harboring a germline T790M mutation responded well to osimertinib with a progression-free survival of more than 30 months and without any unexpected toxicities. Osimertinib is effective for patients with lung squamous cell carcinoma with T790M and L858R mutations. The germline EGFR T790M mutation is associated with genetic susceptibility to lung cancer. The clinical use of next-generation sequencing could maximize the benefits of precision medicine in patients with cancer.

Topics: Acrylamides; Adult; Aniline Compounds; Carcinoma, Adenosquamous; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Germ Cells; Germ-Line Mutation; Humans; Lung Neoplasms; Male; Mutation; Protein Kinase Inhibitors

The role of targeted therapy in patients with lung adenosquamous carcinoma (ASC) has been controversial and it was unclear whether a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) could improve outcomes. This study was designed to evaluate the efficacy of different generations of EGFR TKI therapy in ASC patients with sensitive EGFR mutations.. Patients with non-small cell lung cancer (NSCLC) diagnosed at the Shanghai Chest Hospital between January 2010 and December 2016 were retrospectively reviewed.. A total of 10,037 NSCLC patients tested for EGFR mutations were screened, with primary ASC accounting for 1.4% (139/10,037). Positive EGFR mutations were found in 51.1% (71/139) of ASC patients, including 67 sensitive mutations (19del or 21L858R) and four uncommon mutations (19del + 20T790M, 21L858R + 20T790M, 19L747P + 20Q787Q, and 21L861Q). Sensitive EGFR mutations occurred more frequently in younger (62.0 vs 65.0, p = 0.010), non-smoking (83.6% vs 57.8%, p = 0.002) women (56.7% vs 34.4%, p = 0.014). Among the 36 ASC patients with eligible survival data for the first-generation TKIs, the median progression-free survival (PFS) was 9.3 months (95% CI 6.7-11.9), which was rather similar to the data of adenocarcinoma (9.3 vs 11.4 months, p = 0.294) in our institution as opposed to squamous cell carcinoma (9.3 vs 4.9 months, p < 0.001). The objective response rate (ORR) was 37.9% (11/29), and the disease control rate (DCR) was 86.2% (25/29). After progression on the initial EGFR TKIs, 42.1% of the cases (8/19) had an EGFR T790M mutation detected. A median PFS of 10.2 months (95% CI 5.8-14.5, n = 8) was achieved with treatment using the third-generation TKI. The ORR and DCR were 37.5% (3/8) and 100% (8/8), respectively. The median overall survival reached 38.3 months (95% CI 13.7-62.9).. Targeted therapy showed remarkable efficacy in ASC patients harboring sensitive EGFR mutations, comparable to adenocarcinoma. The application of the third-generation TKI provided an option to prolong survival.

Topics: Acrylamides; Age Factors; Aged; Aniline Compounds; Carcinoma, Adenosquamous; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Protein Kinase Inhibitors; Sex Characteristics; Survival Analysis; Treatment Outcome

Topics: Acrylamides; Aged; Aged, 80 and over; Aniline Compounds; Brain Neoplasms; Carcinoma, Adenosquamous; Disease Progression; ErbB Receptors; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mutation; Piperazines; Pneumonia; Protein Kinase Inhibitors; Steroids