Please use this identifier to cite or link to this item:
https://doi.org/10.21037/tlcr-22-661
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dc.title | Real world efficacy of osimertinib in second line/beyond in patients with metastatic EGFR plus non-small cell lung cancer and role of paired tumour-plasma T790M testing at tyrosine kinase inhibitor resistance | |
dc.contributor.author | Ma, Jun | |
dc.contributor.author | Tan, Sze Huey | |
dc.contributor.author | Yin, Daniel Xing Cheng | |
dc.contributor.author | Tran, Nguyen Tuan Anh | |
dc.contributor.author | San Tan, Gek | |
dc.contributor.author | Lai, Gillianne Geet Yi | |
dc.contributor.author | Ang, Mei-Kim | |
dc.contributor.author | Kanesvaran, Ravindran | |
dc.contributor.author | Jain, Amit | |
dc.contributor.author | Rajasekaran, Tanujaa | |
dc.contributor.author | Tan, Eng-Huat | |
dc.contributor.author | Lim, Tony Kiat Hon | |
dc.contributor.author | Tan, Daniel Shao-Weng | |
dc.contributor.author | Lim, Darren Wan-Teck | |
dc.contributor.author | Ng, Quan Sing | |
dc.contributor.author | Tan, Wan Ling | |
dc.date.accessioned | 2024-06-14T05:44:16Z | |
dc.date.available | 2024-06-14T05:44:16Z | |
dc.date.issued | 2023-04 | |
dc.identifier.citation | Ma, Jun, Tan, Sze Huey, Yin, Daniel Xing Cheng, Tran, Nguyen Tuan Anh, San Tan, Gek, Lai, Gillianne Geet Yi, Ang, Mei-Kim, Kanesvaran, Ravindran, Jain, Amit, Rajasekaran, Tanujaa, Tan, Eng-Huat, Lim, Tony Kiat Hon, Tan, Daniel Shao-Weng, Lim, Darren Wan-Teck, Ng, Quan Sing, Tan, Wan Ling (2023-04). Real world efficacy of osimertinib in second line/beyond in patients with metastatic EGFR plus non-small cell lung cancer and role of paired tumour-plasma T790M testing at tyrosine kinase inhibitor resistance. TRANSLATIONAL LUNG CANCER RESEARCH 12 (4) : 742-753. ScholarBank@NUS Repository. https://doi.org/10.21037/tlcr-22-661 | |
dc.identifier.issn | 2218-6751 | |
dc.identifier.issn | 2226-4477 | |
dc.identifier.uri | https://scholarbank.nus.edu.sg/handle/10635/248897 | |
dc.description.abstract | Background: Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) approved for use in EGFR-mutant lung cancer. We examined its performance in the second/ subsequent line after resistance to first- and second-generation (1/2G) EGFR-TKI. Methods: We reviewed electronic records of 202 patients who received osimertinib from July 2015 to January 2019 in the second/subsequent line after progression on prior EGFR-TKI. Of these, complete data from 193 patients were available. Clinical data including patient characteristics, primary EGFR mutation, T790M mutation status, presence of baseline brain metastases (BM), first-line EGFR-TKI use, and survival outcomes were extracted, and results retrospectively analyzed. Results: Of 193 evaluable patients, 151 (78.2%) were T790M+ (T790M positive) with 96 (49.2%) tissue confirmed; 52% of patients received osimertinib in the second line setting. After median follow up of 37 months, median progression-free survival (PFS) of the entire cohort was 10.3 [95% confidence interval (CI): 8.64–11.50] months and median overall survival (OS) was 20 (95% CI: 15.61–23.13) months. Overall response rate (ORR) to osimertinib was 43% (95% CI: 35.9–50.3%); 48.3% in T790M+ vs. 20% in T790M− (T790M negative) patients. OS in T790M+ patients was 22.6 vs. 7.9 months in T790M− patients (HR 0.43, P=0.001), and PFS was 11.2 vs. 3.1 months respectively (HR 0.52, P=0.01). Tumour T790M+ was significantly associated with longer PFS (P=0.007) and OS (P=0.01) compared to tumour T790M− patients, however this association was not seen with plasma T790M+. Of the 22 patients with paired tumor/plasma T790M testing, response rate (RR) to osimertinib was 30% for those plasma T790M+/tumour T790M−, compared to 63% and 67% for those who were plasma T790M+/tumour T790M+ and plasma T790M−/ tumour T790M+, respectively. By multivariable analysis (MVA), Eastern Cooperative Oncology Group (ECOG) performance status ≥2 was associated with shorter OS (HR 2.53, P<0.001) and PFS (HR 2.10, P<0.001), whereas presence of T790M+ was associated with longer OS (HR 0.50, P=0.008) and PFS (HR 0.57, P=0.027). Conclusions: This cohort demonstrated the efficacy of osimertinib in second line/beyond for EGFR+ (EGFR mutation-positive) non-small cell lung cancer (NSCLC). Tissue T790M result appeared more predictive of osimertinib efficacy compared to plasma, highlighting potential T790M heterogeneity and the advantage with paired tumor-plasma T790M testing at TKI resistance. T790M− disease at resistance remains an unmet treatment need. | |
dc.language.iso | en | |
dc.publisher | AME PUBLISHING COMPANY | |
dc.source | Elements | |
dc.subject | Science & Technology | |
dc.subject | Life Sciences & Biomedicine | |
dc.subject | Oncology | |
dc.subject | Respiratory System | |
dc.subject | MUTATIONS | |
dc.subject | AFATINIB | |
dc.subject | NSCLC | |
dc.subject | TKI | |
dc.subject | TECHNOLOGIES | |
dc.subject | AZD9291 | |
dc.type | Article | |
dc.date.updated | 2024-06-12T13:47:50Z | |
dc.contributor.department | DUKE-NUS MEDICAL SCHOOL | |
dc.contributor.department | DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL) | |
dc.contributor.department | BIOCHEMISTRY | |
dc.description.doi | 10.21037/tlcr-22-661 | |
dc.description.sourcetitle | TRANSLATIONAL LUNG CANCER RESEARCH | |
dc.description.volume | 12 | |
dc.description.issue | 4 | |
dc.description.page | 742-753 | |
dc.published.state | Published | |
Appears in Collections: | Elements Staff Publications |
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