Frontiers in Oncology (Oct 2023)

Sequential treatment in advanced epidermal growth factor receptor-mutated lung adenocarcinoma patients receiving first-line bevacizumab combined with 1st/2nd-generation EGFR-tyrosine kinase inhibitors

  • Ping-Chih Hsu,
  • Ping-Chih Hsu,
  • Chun-Yao Huang,
  • Yu-Ching Lin,
  • Yu-Ching Lin,
  • Yu-Ching Lin,
  • Suey-Haur Lee,
  • Li-Chung Chiu,
  • Li-Chung Chiu,
  • Chiao-En Wu,
  • Chiao-En Wu,
  • Scott Chih-Hsi Kuo,
  • Scott Chih-Hsi Kuo,
  • Jia-Shiuan Ju,
  • Allen Chung-Cheng Huang,
  • Ho-Wen Ko,
  • Ho-Wen Ko,
  • Chin-Chou Wang,
  • Chin-Chou Wang,
  • Cheng-Ta Yang,
  • Cheng-Ta Yang,
  • Cheng-Ta Yang

DOI
https://doi.org/10.3389/fonc.2023.1249106
Journal volume & issue
Vol. 13

Abstract

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IntroductionThe clinical outcomes of sequential treatment of advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients with first-line bevacizumab combined with 1st/2nd-generation EGFR-TKIs are unclear. Thus, we aimed to analyze the outcomes of these patients.Methods Between January 2015 and December 2020, data for 102 advanced EGFR-mutated lung adenocarcinoma patients receiving first-line bevacizumab combined with erlotinib or afatinib followed by treatments at multiple institutions were retrospectively analyzed. All patients with progressive disease (PD) after first-line therapy underwent secondary T790M mutation detection.Results The secondary T790M mutation positive rate of all study patients was 57.9%. First-line erlotinib use and progression-free survival (PFS) after first-line therapy > 12 months were positively associated with the T790M mutation (P <0.05). The response rates (RRs) to second-line treatments were 51.7% and 22.7% for the osimertinib and nonosimertinib groups, respectively (P = 0.001). The median PFS associated with second-line osimertinib and nonosimertinib therapy was 13.7 and 7.1 months, respectively (hazard ratio (HR) = 0.38; 95% confidence interval (CI), 0.23–0.63; P< 0.001). Patients with a secondary T790M mutation receiving second-line osimertinib treatment had a median overall survival (OS) of 54.3 months, and the median OS was 31.9 months for non-T790M-mutated patients receiving second-line nonosimertinib treatments (HR = 0.36; CI: 0.21–0.62, P < 0.001).Conclusion The majority of acquired resistance to first-line bevacizumab combined with 1st/2nd-generation EGFR-TKIs is associated with the T790M mutation. Sequential osimertinib treatment in patients with positive secondary T790M mutation is associated with better outcomes among these patients.

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