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

doi:10.3389/fonc.2023.1249106

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

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

1 Scopus citations

Abstract

INTRODUCTION: The 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.

Original language	English
Article number	1249106
Pages (from-to)	1249106
Journal	Frontiers in Oncology
Volume	13
DOIs	https://doi.org/10.3389/fonc.2023.1249106
State	Published - 10 2023

Bibliographical note

Keywords

T790M
bevacizumab
epidermal growth factor receptor mutation
lung adenocarcinoma
osimertinib
tyrosine kinase inhibitor

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3389/fonc.2023.1249106

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Hsu, P. C., Huang, C. Y., Lin, Y. C., Lee, S. H., Chiu, L. C., Wu, C. E., Kuo, S. C. H., Ju, J. S., Huang, A. C. C., Ko, H. W., Wang, C. C., & Yang, C. T. (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. Frontiers in Oncology, 13, 1249106. Article 1249106. https://doi.org/10.3389/fonc.2023.1249106

@article{05f218fc31c541b0858580b34bce8c2b,

title = "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",

abstract = "INTRODUCTION: The 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.",

keywords = "T790M, bevacizumab, epidermal growth factor receptor mutation, lung adenocarcinoma, osimertinib, tyrosine kinase inhibitor",

author = "Hsu, \{Ping Chih\} and Huang, \{Chun Yao\} and Lin, \{Yu Ching\} and Lee, \{Suey Haur\} and Chiu, \{Li Chung\} and Wu, \{Chiao En\} and Kuo, \{Scott Chih Hsi\} and Ju, \{Jia Shiuan\} and Huang, \{Allen Chung Cheng\} and Ko, \{Ho Wen\} and Wang, \{Chin Chou\} and Yang, \{Cheng Ta\}",

note = "Copyright {\textcopyright} 2023 Hsu, Huang, Lin, Lee, Chiu, Wu, Kuo, Ju, Huang, Ko, Wang and Yang.",

year = "2023",

month = oct,

doi = "10.3389/fonc.2023.1249106",

language = "英语",

volume = "13",

pages = "1249106",

journal = "Frontiers in Oncology",

issn = "2234-943X",

publisher = "Frontiers Media SA",

}

Hsu, PC, Huang, CY, Lin, YC, Lee, SH, Chiu, LC, Wu, CE, Kuo, SCH, Ju, JS, Huang, ACC, Ko, HW, Wang, CC & Yang, CT 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', Frontiers in Oncology, vol. 13, 1249106, pp. 1249106. https://doi.org/10.3389/fonc.2023.1249106

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. / Hsu, Ping Chih; Huang, Chun Yao; Lin, Yu Ching et al.
In: Frontiers in Oncology, Vol. 13, 1249106, 10.2023, p. 1249106.

Research output: Contribution to journal › Journal Article › peer-review

TY - JOUR

T1 - 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

AU - Hsu, Ping Chih

AU - Huang, Chun Yao

AU - Lin, Yu Ching

AU - Lee, Suey Haur

AU - Chiu, Li Chung

AU - Wu, Chiao En

AU - Kuo, Scott Chih Hsi

AU - Ju, Jia Shiuan

AU - Huang, Allen Chung Cheng

AU - Ko, Ho Wen

AU - Wang, Chin Chou

AU - Yang, Cheng Ta

PY - 2023/10

Y1 - 2023/10

N2 - INTRODUCTION: The 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.

AB - INTRODUCTION: The 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.

KW - T790M

KW - bevacizumab

KW - epidermal growth factor receptor mutation

KW - lung adenocarcinoma

KW - osimertinib

KW - tyrosine kinase inhibitor

UR - https://www.scopus.com/pages/publications/85174639098

U2 - 10.3389/fonc.2023.1249106

DO - 10.3389/fonc.2023.1249106

M3 - 文章

C2 - 37854677

AN - SCOPUS:85174639098

SN - 2234-943X

VL - 13

SP - 1249106

JO - Frontiers in Oncology

JF - Frontiers in Oncology

M1 - 1249106

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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