TY - JOUR
T1 - Investigation of efficacy and acquired resistance for EGFR-TKI plus bevacizumab as first-line treatment in patients with EGFR sensitive mutant non-small cell lung cancer in a Real world population
AU - Zeng, Liang
AU - Xiao, Lili
AU - Jiang, Wenjuan
AU - Yang, Haiyan
AU - Hu, Dandan
AU - Xia, Chen
AU - Li, Yizhi
AU - Zhou, Chunhua
AU - Xiong, Yi
AU - Liu, Li
AU - Liao, Dehua
AU - Guan, Rui
AU - Li, Kunyan
AU - Wang, Jing
AU - Zhang, Yongchang
AU - Yang, Nong
AU - Mansfield, Aaron S.
N1 - Funding Information:
Yongchang Zhang was the principal investigator (PI) for this study and was involved in project oversight, organization, data collection and auditing; Liang Zeng, Lili Xiao, Chunhua Zhou, Yi Xiong, Li Liu, Wenjuan Jiang, Haiyan Yang and Yijuan Hu collected the clinical data; Kunyan Li and Jing Wang performed statistical analyses; Yongchang Zhang and Nong Yang gave critical comments and suggestions; Aaron S. Mansfield, Dehua Liao and Dandan Hu revised the paper; all authors approved the final version of the manuscript. This work was financially supported by grants from the National Natural Science Foundation of China (NO.81401902 and NO.81501992) and Natural Science Foundation of Hunan Province (2018RS3106, 2018JJ2238 and 2017SK2134).
Funding Information:
Yongchang Zhang was the principal investigator (PI) for this study and was involved in project oversight, organization, data collection and auditing; Liang Zeng, Lili Xiao, Chunhua Zhou, Yi Xiong, Li Liu, Wenjuan Jiang, Haiyan Yang and Yijuan Hu collected the clinical data; Kunyan Li and Jing Wang performed statistical analyses; Yongchang Zhang and Nong Yang gave critical comments and suggestions; Aaron S. Mansfield, Dehua Liao and Dandan Hu revised the paper; all authors approved the final version of the manuscript. This work was financially supported by grants from the National Natural Science Foundation of China (NO. 81401902 and NO. 81501992 ) and Natural Science Foundation of Hunan Province ( 2018RS3106 , 2018JJ2238 and 2017SK2134 ).
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/3
Y1 - 2020/3
N2 - Objectives: We aimed to investigate the clinical efficacy of EGFR tyrosine kinase inhibitor (TKI, T) plus bevacizumab (an antiangiogenic therapy, A) in a real-world population and to provide insights into their mechanism of resistance. Methods: This study included 256 NSCLC patients harboring EGFR sensitizing mutations (EGFR 19del and L858R) who underwent nextgeneration sequencing (NGS) with 168-gene panel prior to treatment between Jan 2015 to Aug 2018. Cohort A included 60 patients treated with A + T; while cohort B consisted of 120 patients treated with EGFR-TKI monotherapy with the patients identified using Propensity Score Matching (Ratio of 1:2). Clinical outcomes and potential resistance mechanism were evaluated. Results: Baseline clinical characteristics were not significantly different between Cohort A and B. Compared with cohort B, cohort A had significantly better overall response rate (95% vs 74.2%, p = 0.001) and longer median progression-free survival (PFS, 16.5m vs.12.0 m, HR = 0.7, p = 0.001). Until Jan 2019, 31 and 103 patients in cohort A and B, respectively, were evaluated with progressive disease and underwent tissue re-biopsy and NGS profiling with 168-gene panel. In cohort B, T790M was the predominant acquired resistance mechanism, detected in 51.5% (53/103) of progressive tumors, followed by amplifications in EGFR (15.5%, 16/103) and MET (6.8%, 7/103). Contrastingly, cohort A had a significantly lower rate of T790 M mutation (35.5%, 11/31, p = 0.0003), followed by mutations in TP53 (29.0%, 9/31), RB1 (9.7%, 3/31), SMAD4 (3.2%, 1/31) and EGFR V834 L (3.2%, 1/31) and amplifications in EGFR (9.7%, 3/31), and MET(6.5%, 2/31). Conclusion: Treatment with first-line A + T significantly extends the time to progression and increases the response rate with acceptable safety profile. T790 M was the most common acquired resistance mechanism but it was less common in patients who received A + T.
AB - Objectives: We aimed to investigate the clinical efficacy of EGFR tyrosine kinase inhibitor (TKI, T) plus bevacizumab (an antiangiogenic therapy, A) in a real-world population and to provide insights into their mechanism of resistance. Methods: This study included 256 NSCLC patients harboring EGFR sensitizing mutations (EGFR 19del and L858R) who underwent nextgeneration sequencing (NGS) with 168-gene panel prior to treatment between Jan 2015 to Aug 2018. Cohort A included 60 patients treated with A + T; while cohort B consisted of 120 patients treated with EGFR-TKI monotherapy with the patients identified using Propensity Score Matching (Ratio of 1:2). Clinical outcomes and potential resistance mechanism were evaluated. Results: Baseline clinical characteristics were not significantly different between Cohort A and B. Compared with cohort B, cohort A had significantly better overall response rate (95% vs 74.2%, p = 0.001) and longer median progression-free survival (PFS, 16.5m vs.12.0 m, HR = 0.7, p = 0.001). Until Jan 2019, 31 and 103 patients in cohort A and B, respectively, were evaluated with progressive disease and underwent tissue re-biopsy and NGS profiling with 168-gene panel. In cohort B, T790M was the predominant acquired resistance mechanism, detected in 51.5% (53/103) of progressive tumors, followed by amplifications in EGFR (15.5%, 16/103) and MET (6.8%, 7/103). Contrastingly, cohort A had a significantly lower rate of T790 M mutation (35.5%, 11/31, p = 0.0003), followed by mutations in TP53 (29.0%, 9/31), RB1 (9.7%, 3/31), SMAD4 (3.2%, 1/31) and EGFR V834 L (3.2%, 1/31) and amplifications in EGFR (9.7%, 3/31), and MET(6.5%, 2/31). Conclusion: Treatment with first-line A + T significantly extends the time to progression and increases the response rate with acceptable safety profile. T790 M was the most common acquired resistance mechanism but it was less common in patients who received A + T.
KW - Bevacizumab plus EGFR-TKI
KW - NSCLC
KW - PFS
KW - Resistance mechanism
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U2 - 10.1016/j.lungcan.2020.01.009
DO - 10.1016/j.lungcan.2020.01.009
M3 - Article
C2 - 31982639
AN - SCOPUS:85078080562
VL - 141
SP - 82
EP - 88
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
ER -