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

Front Oncol. 2023 Oct 3:13:1249106. doi: 10.3389/fonc.2023.1249106. eCollection 2023.

Authors

Ping-Chih Hsu^{1

2}, Chun-Yao Huang³, Yu-Ching Lin^{2

4

5}, Suey-Haur Lee⁶, Li-Chung Chiu^{1

2}, Chiao-En Wu^{2

7}, Scott Chih-Hsi Kuo^{1

2}, Jia-Shiuan Ju¹, Allen Chung-Cheng Huang¹, Ho-Wen Ko^{1

2}, Chin-Chou Wang^{2

6}, Cheng-Ta Yang^{1

8

9}

Affiliations

¹ Division of Thoracic Medicine, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
² Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ Department of Pulmonary and Critical Care, Buddhist Tzu Chi General Hospital, New Taipei City, Taiwan.
⁴ Division of Thoracic Oncology, Department of Respiratory and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi County, Taiwan.
⁵ Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi County, Taiwan.
⁶ Division of Pulmonary & Critical Care Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
⁷ Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
⁸ Department of Internal Medicine, Taoyuan Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁹ Department of Respiratory Therapy, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

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.

Grants and funding

This study was supported by the Taiwan Ministry of Science and Technology (MOST) (grant no. 111-2628-B-182-011– and 111-2628-B-182A-003- to P-CH).