osimertinib and Pleural-Effusion

A man in his 70s was detected an infiltrative shadow on the right lung. A bronchoscopy confirmed the diagnosis of adenocarcinoma of the lung, classified as cT2bN2M0 stage IIIA, with a deletion mutation in

Topics: Adenocarcinoma; Cardiotoxicity; ErbB Receptors; Humans; Lung; Male; Pleural Effusion

This study was to evaluate anti-tumor efficacy of osimertinib in patients positive for acquired epidermal growth factor receptor (EGFR) T790M mutation in liquid biopsy using plasma, bronchoalveolar lavage fluid (BALF) or bronchial washing fluid (BWF), and pleural effusion.. Among patients benefited from previous EGFR‒tyrosine kinase inhibitor treatment followed by treatment failure, patients in whom T790M mutations are detected in at least one of the samples including tumor tissues, BALF/BWF, plasma, and pleural effusion were enrolled. T790M mutation was detected by extracting cell free DNA from liquid biopsy samples, using PANA Mutyper. Objective response rate (ORR) and progression-free survival (PFS) with osimertinib treatment were evaluated.. Between January 2018 and December 2019, 63 patients were enrolled and received osimertinib. Mean age was 63 years, and 38 (60.3%) were female. Twenty-six patients had T790M mutation in both liquid and tissue samples (group A), 19 patients had only in tissue biopsy samples (group B), and 18 patients had T790M mutation only in liquid biopsy samples (group C). ORR in overall population was 63.5%, and was 61.5% in group A, 68.4% in group B, and 61.1% in group C, respectively. Median PFS in overall patients was 15.6 months (95% confidence interval, 10.7 to 24.2). There was no significant difference in ORR or PFS between groups.. Osimertinib showed favorable efficacy in lung cancer patients with acquired resistance to prior EGFR-TKI therapies, who screened positive for harboring T790M mutation detected from cell free DNA extracted from plasma, BALF/BWF, and pleural effusion.

Topics: Acrylamides; Aniline Compounds; Antineoplastic Agents; Bronchoalveolar Lavage Fluid; Carcinoma, Non-Small-Cell Lung; Cell-Free Nucleic Acids; ErbB Receptors; Female; Humans; Indoles; Liquid Biopsy; Lung Neoplasms; Male; Middle Aged; Mutation; Pleural Effusion; Protein Kinase Inhibitors; Pyrimidines

Osimertinib is a standard first-line treatment for advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Although malignant pleural effusion (PE) is a common clinical problem in NSCLC, information about the efficacy of osimertinib in patients with PE is limited, especially regarding its efficacy in EGFR T790M-negative patients with PE remains unclear.. We retrospectively reviewed the medical records of patients with NSCLC harboring EGFR mutations who were treated with osimertinib in our institution between May 2016 and December 2020.. A total of 63 patients with EGFR mutated NSCLC were treated with osimertinib; 33 (12 with PE) had no EGFR T790M mutation, while 30 (12 with PE) had EGFR T790M mutation. In EGFR T790M-negative NSCLC, the progression-free survival (PFS) of the patients with PE was comparable to that of the patients without PE (median PFS 19.8 vs. 19.8 months, p = 0.693). In EGFR T790M- positive NSCLC, the PFS and overall survival (OS) of the patients with PE were significantly shorter than those of the patients without PE (median PFS 16.8 vs. 8.3 months, p = 0.003; median OS 44.9 vs. 14.2 months, p = 0.007). In the multivariate analysis, the presence of PE was independently associated with shorter PFS and OS in EGFR T790M-positive NSCLC patients, but not EGFR T790M-negative patients.. These data suggest the efficacy of osimertinib may differ between EGFR T790M-positive and -negative NSCLC patients with PE.

Topics: Acrylamides; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Pleural Effusion; Protein Kinase Inhibitors; Retrospective Studies

Topics: Acrylamides; Adenocarcinoma of Lung; Aniline Compounds; Carcinoma, Small Cell; Humans; Indoles; Lung Neoplasms; Pleural Effusion; Pleural Effusion, Malignant; Pyrimidines

Osimertinib has demonstrated promising efficacy in patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC). We investigated the efficacy of osimertinib in such patients presenting with pleural effusion, which has been unclear to date.. The medical records of all patients treated with osimertinib for advanced NSCLC with EGFR T790M between April 2016 and July 2017 at our Institution were retrospectively reviewed. Time to treatment failure (TTF) and overall survival (OS) were determined as endpoints.. Twenty-three patients (seven with pleural effusions) were treated with osimertinib. Patients with pleural effusion had significantly shorter median TTF than those without (3.7 vs. 12.8 months, respectively, p=0.021), as well as shorter median OS (7.8 months vs. not attained, respectively, p=0.002). Metastasis to the brain, bone, and liver did not significantly influence our endpoints.. Osimertinib monotherapy is less effective in patients with NSCLC with pleural effusions.

Topics: Acrylamides; Adult; Aged; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Mutation; Piperazines; Pleural Effusion; Protein Kinase Inhibitors; Retrospective Studies; Treatment Outcome

A 90-year-old woman was referred to our hospital because of dyspnea with pleural effusion that was detected using a chest X-ray. Pleural fluid cell block specimens from the left pleural effusion were shown to be an adenocarcinoma harboring an epidermal growth factor receptor(EGFR)gene mutation(L858R). Erlotinib was administered and the patient responded to treatment for 15 months. Subsequent re-accumulation of the left pleural effusion was detected, and re-evaluation using cell block specimens revealed EGFR T790M mutation positivity. Osimertinib was initiated and the patient responded to treatment for 11 months. Re-evaluation of the left pleural effusion upon failure of osimertinib treatment revealed EGFR T790M mutation negativity. Hence this report summarizes the case of osimertinib therapy being administered to a 90-year-old patient who had EGFR T790M mutation positivity based on a pleural fluid cell block.

Topics: Acrylamides; Adenocarcinoma; Adenocarcinoma of Lung; Aged, 80 and over; Aniline Compounds; Antineoplastic Agents; ErbB Receptors; Female; Humans; Lung Neoplasms; Mutation; Piperazines; Pleural Effusion