Scholarlink

Background <p>Epidermal growth factor receptor (EGFR)-driven non-small cell lung cancer (eLC) is a leading cause of death. The FLAURA study showed that upfront&#xa0;osimertinib&#xa0;(U-OSI) led to better overall survival (OS) than gefitinib or erlotinib, regardless of T790M status in advanced disease. However, if sequenced optimally, sequential OSI (S-OSI) in T790M-positive patients after first- or second-generation EGFR-tyrosine kinase inhibitors (F-S-EGFR-TKI) should theoretically lead to better OS than U-OSI.</p> Objective <p>To identify the best sequencing strategy in this group of patients.</p> Patients and Methods <p>A multicentre retrospective study was conducted on treatment-naive&#xa0;eLC&#xa0;patients who had received an F-S- EGFR-TKI between 1 January 2016 and 31 December 2020 in three tertiary NHS hospitals in the UK. Compliance to national recommendation of T790M testing was analysed. Survival outcomes of T790M testing and S-OSI were estimated with the Kaplan–Meier and Cox Proportional Hazard models.</p> Results <p>In 84/122 evaluable patients, after F-S-EGFR-TKI, only 50% of the patients were offered a T790M biopsy, owing to rapid progression and reduced fitness. Of which, 59.5% of the patients tested positive and had S-OSI. Median OS for the T790M-tested cohort, regardless of positivity and S-OSI, was 54.0 months vs 8.9 months in those not tested (<i>P</i> = &lt; 0.001).&#xa0;Median OS of S-OSI in T790M-positive patients was 64.0 months vs 34.9 months in the T790M-negative cohort (<i>P</i> &lt; 0.0001). On multivariable analysis, S-OSI was associated with better OS (HR 1.841; 95% CI 1.052–3.221; <i>P</i> = 0.0325), whereas performance status (HR 2. 256; 95% CI 1.151–4.422, <i>P</i> = 0.0178), presence of baseline intracranial disease (HR 2 .022; 95% CI 1.144–3.575, <i>P</i> = 0. 0115),&#xa0;the male sex (HR 2.265; 95% CI 1.302–3.939; <i>P</i> = 0.0038) and non-exon 19 deletion mutations (HR 1.610; 95% CI 1.112–2.331, <i>P</i> = 0.0116) were associated with a higher risk of death.</p> Conclusions <p>High performance status and intracranial disease should be indications for U-OSI for a higher chance of response. For fitter patients, F-S-EGFR-TKI followed by T790M biopsy +/− S-OSI appears to confer better-than-expected OS in the entire cohort in the real-world setting, regardless of T790M positivity. Given the clinical benefit and potential cost-effectiveness of this approach, S-OSI should be considered a favourable option in this group of patients, especially in resource-deprived settings.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Real-World Outcomes of T790M Mutation Testing and Sequential Osimertinib in EGFR-Positive Advanced Non-small Cell Lung Cancer: A Revisited Strategy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月2日

查看全文
  • Kelvin Yan,
  • Arizah Bakhtiah,
  • Shweta Hota,
  • Joanne Evans,
  • Frankie Mo

摘要

Background

Epidermal growth factor receptor (EGFR)-driven non-small cell lung cancer (eLC) is a leading cause of death. The FLAURA study showed that upfront osimertinib (U-OSI) led to better overall survival (OS) than gefitinib or erlotinib, regardless of T790M status in advanced disease. However, if sequenced optimally, sequential OSI (S-OSI) in T790M-positive patients after first- or second-generation EGFR-tyrosine kinase inhibitors (F-S-EGFR-TKI) should theoretically lead to better OS than U-OSI.

Objective

To identify the best sequencing strategy in this group of patients.

Patients and Methods

A multicentre retrospective study was conducted on treatment-naive eLC patients who had received an F-S- EGFR-TKI between 1 January 2016 and 31 December 2020 in three tertiary NHS hospitals in the UK. Compliance to national recommendation of T790M testing was analysed. Survival outcomes of T790M testing and S-OSI were estimated with the Kaplan–Meier and Cox Proportional Hazard models.

Results

In 84/122 evaluable patients, after F-S-EGFR-TKI, only 50% of the patients were offered a T790M biopsy, owing to rapid progression and reduced fitness. Of which, 59.5% of the patients tested positive and had S-OSI. Median OS for the T790M-tested cohort, regardless of positivity and S-OSI, was 54.0 months vs 8.9 months in those not tested (P = < 0.001). Median OS of S-OSI in T790M-positive patients was 64.0 months vs 34.9 months in the T790M-negative cohort (P < 0.0001). On multivariable analysis, S-OSI was associated with better OS (HR 1.841; 95% CI 1.052–3.221; P = 0.0325), whereas performance status (HR 2. 256; 95% CI 1.151–4.422, P = 0.0178), presence of baseline intracranial disease (HR 2 .022; 95% CI 1.144–3.575, P = 0. 0115), the male sex (HR 2.265; 95% CI 1.302–3.939; P = 0.0038) and non-exon 19 deletion mutations (HR 1.610; 95% CI 1.112–2.331, P = 0.0116) were associated with a higher risk of death.

Conclusions

High performance status and intracranial disease should be indications for U-OSI for a higher chance of response. For fitter patients, F-S-EGFR-TKI followed by T790M biopsy +/− S-OSI appears to confer better-than-expected OS in the entire cohort in the real-world setting, regardless of T790M positivity. Given the clinical benefit and potential cost-effectiveness of this approach, S-OSI should be considered a favourable option in this group of patients, especially in resource-deprived settings.