T790M Mutation-positive Lung Cancer Research Articles

Triple positive lung cancer: A case report

Background: Targeted therapies in nonsmall cell lung cancer has changed the landscape of management and carved the disease in to more different sub types. Despite of considerable initial response to 1st generation and 2nd generation tyrosine kinase inhibitors patients develop resistance in the due course. Secondary mutations are due to threonine and methionine substitution at 790 (T790M) of EGFR. T790M mutation are resistant to 1st and 2nd generation TKI.Osimertinib is a irreversible third generation epidermal growth factor receptor tyrosine kinase inhibitor effective against EGFR T790M mutation positive lung cancer. Patients are inescapable of developing resistance with Osimertinib in spite of initial response and leaving no further definite therapeutic options. In 20-30% patients with osimertinib resistance develop EGFR C797S mutation. Our objective is to show the patient journey with primary, secondary mutation withT790M and tertiary mutation in C797S. Key Messages: Prospective molecular tumor profiling is now the standard of care in the treatment of metastatic NSCLC. Re-biopsy or liquid biopsy on progression of first and second line TKI to look for T790M has already been in routine practice. Re-biopsy or liquid biopsy on progression of third line TKI and molecular profiling can guide us in further management.

Non–Small Cell Lung Cancer with Resistance to EGFR-TKI Therapy: CT Characteristics of T790M Mutation–positive Cancer

Purpose To evaluate the clinical and CT characteristics of T790M mutation-positive non-small cell lung cancer (NSCLC) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy failure. Materials and Methods A retrospective study of 304 patients with NSCLC who underwent rebiopsy after first-line EGFR-TKI therapy was conducted. Rebiopsy methods included CT- or fluoroscopy-guided lung biopsies (n = 105), endobronchial US- or bronchofibroscopy-guided biopsies (n = 66), pleural fluid analysis (n = 47), other solid organ biopsies (n = 43), US-guided axillary or supraclavicular lymph node biopsies (n = 31), and cerebrospinal fluid analysis (n = 12). CT findings at the initial diagnosis and rebiopsy were analyzed. Progression-free survival, the duration from the start of TKI therapy to rebiopsy, and survival were calculated. Results At rebiopsy, 144 (47.4%) patients were T790M mutation positive. The percentages of T790M mutation-positive NSCLCs were similar in 106 patients with rebiopsy of the lungs (53 [50%] of 106) and in 77 patients with rebiopsy of the primary lung lesions (36 [47%] of 77). T790M mutation positivity was associated with peripheral tumors (odds ratio [OR], 2.6; P = .01), pleural tag (OR, 5.0; P < .001), and air bronchogram (OR, 4.0; P = .006) at CT after TKI failure. The duration from the start of TKI therapy to rebiopsy was longer in T790M mutation-positive than in T790M mutation-negative patients (20.5 vs 13.6 months; P < .001). Cumulative survival from the time of rebiopsy to the last follow-up was significantly longer in patients with T790M mutation-positive lung cancers (P = .014). However, median survival time after rebiopsy was not statistically different between patients with and those without T790M mutation. Conclusion Peripheral tumor location with vascular convergence, the presence of a pleural tag, and air bronchogram of lung lesions at CT at the time of rebiopsy were significantly associated with T790M mutation in patients with non-small cell lung cancer after first-line epidermal growth factor receptor-tyrosine kinase inhibitor therapy failure. © RSNA, 2018 Online supplemental material is available for this article.