T790M mutation and clinical outcomes with osimertinib in patients with epidermal growth factor receptor-mutant nonsmall cell lung cancer
Introduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors TKIs) are highly effective in EGFR-mutant advanced lung cancer. The most common resistance mechanism to EGFR-TKI is the development of T790M mutation in Exon 20. Osimertinib, a highly selective EGFR-TKI, has been approv...
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| Format: | Article |
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Thieme Medical and Scientific Publishers Pvt. Ltd.
2019-01-01
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| Series: | Indian Journal of Medical and Paediatric Oncology |
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| Online Access: | http://www.ijmpo.org/article.asp?issn=0971-5851;year=2019;volume=40;issue=1;spage=73;epage=78;aulast= |
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| author | Ravi Jaiswal Rakesh Pinninti M VT Krishna Mohan A Santa Pavan Kumar Boyella Lavanya Nambaru Sudha S Murthy K Veeriah Chowdary Senthil Rajappa |
| author_facet | Ravi Jaiswal Rakesh Pinninti M VT Krishna Mohan A Santa Pavan Kumar Boyella Lavanya Nambaru Sudha S Murthy K Veeriah Chowdary Senthil Rajappa |
| author_sort | Ravi Jaiswal |
| collection | DOAJ |
| description | Introduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors TKIs) are highly effective in EGFR-mutant advanced lung cancer. The most common resistance mechanism to EGFR-TKI is the development of T790M mutation in Exon 20. Osimertinib, a highly selective EGFR-TKI, has been approved for use in patients who progress on the first-line TKI and harbor the T790M mutation. Objective: The primary objective is to prospectively study the incidence of T790M mutation in patients who progress on the first-line EGFR-TKI. Secondary objectives include clinical characteristics that predict for T790M mutation and outcomes with osimertinib. Materials and Methods: This single-center, prospective observational study included 90 patients who progressed on first-line EGFR TKI. All patients had DNA extracted from tissue re-biopsy or plasma circulating tumor DNA (re-biopsy was not feasible or inadequate). T790M mutation was detected using amplification refractory mutation system-polymerase chain reaction, and patients harboring T790M mutation were started on osimertinib (80 mg once daily) until progression or unacceptable side effects. Results: At progression, T790M mutation was detected in 47/90 patients (52.2%). On binary logistic regression model analysis, variables that were independently predictive of the development of T790M were younger age (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.14–16.6, P = 0.031); nonerlotinib TKI use (OR 8.3, 95% CI 1.24–55.8, P = 0.029); and pure adenocarcinoma histology (OR 6.2, 95% CI 1.60–24.7, P = 0.008). Forty-six patients were started on osimertinib. The overall response rate and median progression-free survival were 65.21% and 12.45 months (standard deviation [SD] 1.03, 95% CI 10.41–14.48), respectively. Osimertinib was well tolerated with most toxicities being Grade 1 and 2 diarrhea and skin rash. Conclusions: In our prospective cohort, half of all patients had a T790M mutation at progression on the first-line EGFR TKI. Tissue biopsy is feasible in the majority of patients. Clinical outcomes with osimertinib were consistent with those reported. |
| format | Article |
| id | doaj-art-7e86b86a9c4c4c4b91301ded77cafbf3 |
| institution | DOAJ |
| issn | 0971-5851 0975-2129 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Thieme Medical and Scientific Publishers Pvt. Ltd. |
| record_format | Article |
| series | Indian Journal of Medical and Paediatric Oncology |
| spelling | doaj-art-7e86b86a9c4c4c4b91301ded77cafbf32025-08-20T03:03:51ZengThieme Medical and Scientific Publishers Pvt. Ltd.Indian Journal of Medical and Paediatric Oncology0971-58510975-21292019-01-01401737810.4103/ijmpo.ijmpo_215_18T790M mutation and clinical outcomes with osimertinib in patients with epidermal growth factor receptor-mutant nonsmall cell lung cancerRavi JaiswalRakesh PinnintiM VT Krishna MohanA SantaPavan Kumar BoyellaLavanya NambaruSudha S MurthyK Veeriah ChowdarySenthil RajappaIntroduction: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors TKIs) are highly effective in EGFR-mutant advanced lung cancer. The most common resistance mechanism to EGFR-TKI is the development of T790M mutation in Exon 20. Osimertinib, a highly selective EGFR-TKI, has been approved for use in patients who progress on the first-line TKI and harbor the T790M mutation. Objective: The primary objective is to prospectively study the incidence of T790M mutation in patients who progress on the first-line EGFR-TKI. Secondary objectives include clinical characteristics that predict for T790M mutation and outcomes with osimertinib. Materials and Methods: This single-center, prospective observational study included 90 patients who progressed on first-line EGFR TKI. All patients had DNA extracted from tissue re-biopsy or plasma circulating tumor DNA (re-biopsy was not feasible or inadequate). T790M mutation was detected using amplification refractory mutation system-polymerase chain reaction, and patients harboring T790M mutation were started on osimertinib (80 mg once daily) until progression or unacceptable side effects. Results: At progression, T790M mutation was detected in 47/90 patients (52.2%). On binary logistic regression model analysis, variables that were independently predictive of the development of T790M were younger age (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.14–16.6, P = 0.031); nonerlotinib TKI use (OR 8.3, 95% CI 1.24–55.8, P = 0.029); and pure adenocarcinoma histology (OR 6.2, 95% CI 1.60–24.7, P = 0.008). Forty-six patients were started on osimertinib. The overall response rate and median progression-free survival were 65.21% and 12.45 months (standard deviation [SD] 1.03, 95% CI 10.41–14.48), respectively. Osimertinib was well tolerated with most toxicities being Grade 1 and 2 diarrhea and skin rash. Conclusions: In our prospective cohort, half of all patients had a T790M mutation at progression on the first-line EGFR TKI. Tissue biopsy is feasible in the majority of patients. Clinical outcomes with osimertinib were consistent with those reported.http://www.ijmpo.org/article.asp?issn=0971-5851;year=2019;volume=40;issue=1;spage=73;epage=78;aulast=Epidermal growth factor receptorliquid biopsylung cancerosimertinibre-biopsyT790M |
| spellingShingle | Ravi Jaiswal Rakesh Pinninti M VT Krishna Mohan A Santa Pavan Kumar Boyella Lavanya Nambaru Sudha S Murthy K Veeriah Chowdary Senthil Rajappa T790M mutation and clinical outcomes with osimertinib in patients with epidermal growth factor receptor-mutant nonsmall cell lung cancer Indian Journal of Medical and Paediatric Oncology Epidermal growth factor receptor liquid biopsy lung cancer osimertinib re-biopsy T790M |
| title | T790M mutation and clinical outcomes with osimertinib in patients with epidermal growth factor receptor-mutant nonsmall cell lung cancer |
| title_full | T790M mutation and clinical outcomes with osimertinib in patients with epidermal growth factor receptor-mutant nonsmall cell lung cancer |
| title_fullStr | T790M mutation and clinical outcomes with osimertinib in patients with epidermal growth factor receptor-mutant nonsmall cell lung cancer |
| title_full_unstemmed | T790M mutation and clinical outcomes with osimertinib in patients with epidermal growth factor receptor-mutant nonsmall cell lung cancer |
| title_short | T790M mutation and clinical outcomes with osimertinib in patients with epidermal growth factor receptor-mutant nonsmall cell lung cancer |
| title_sort | t790m mutation and clinical outcomes with osimertinib in patients with epidermal growth factor receptor mutant nonsmall cell lung cancer |
| topic | Epidermal growth factor receptor liquid biopsy lung cancer osimertinib re-biopsy T790M |
| url | http://www.ijmpo.org/article.asp?issn=0971-5851;year=2019;volume=40;issue=1;spage=73;epage=78;aulast= |
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