Primary tumor consolidative therapy improves the outcomes of patients with advanced EGFR-mutant lung adenocarcinoma treated with first-line osimertinib

Jia-Jun Wu; Jeng-Sen Tseng; Zhe-Rong Zheng; Cheng-Hsiang Chu; Kun-Chieh Chen; Mong-Wei Lin; Yen-Hsiang Huang; Kuo-Hsuan Hsu; Tsung-Ying Yang; Sung-Liang Yu; Jin-Shing Chen; Chao-Chi Ho; Gee-Chen Chang

doi:10.1177/17588359231220606

Primary tumor consolidative therapy improves the outcomes of patients with advanced EGFR-mutant lung adenocarcinoma treated with first-line osimertinib

Ther Adv Med Oncol. 2024 Jan 3:16:17588359231220606. doi: 10.1177/17588359231220606. eCollection 2024.

Authors

Jia-Jun Wu^{1

2

3}, Jeng-Sen Tseng^{4

5

6

7}, Zhe-Rong Zheng^{1

2

3}, Cheng-Hsiang Chu^{1

2

3}, Kun-Chieh Chen^{1

2

3}, Mong-Wei Lin⁸, Yen-Hsiang Huang^{4

7}, Kuo-Hsuan Hsu⁹, Tsung-Ying Yang^{4

10}, Sung-Liang Yu^{11

12}, Jin-Shing Chen^{13

14}, Chao-Chi Ho¹⁵, Gee-Chen Chang^{1

2

16

6}

Affiliations

¹ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
² School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
³ Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁴ Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
⁵ Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
⁶ Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
⁷ College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁸ Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
⁹ Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
¹⁰ Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan.
¹¹ Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
¹² Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
¹³ Division of Thoracic Surgery, Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, No. 7, Chung-Shan South Road, Taipei 10002, Taiwan.
¹⁴ Department of Surgical Oncology, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan.
¹⁵ Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10002, Taiwan.
¹⁶ Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, No. 110, Sec. 1, Chien-kuo North Road, Taichung 402, Taiwan.

Abstract

Background: Patients with advanced epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LAD) inevitably experience drug resistance following treatment with EGFR-tyrosine kinase inhibitors (TKIs).

Objectives: We aimed to analyze the effect of primary tumor consolidative therapy (PTCT) on patients treated with first-line osimertinib.

Design and methods: This retrospective cohort study was conducted in patients with advanced stage III or stage IV LAD with EGFR-sensitizing mutations (exon 19 deletion or L858R mutation) with disease control after first-line osimertinib. A curative dose of primary tumor radiotherapy or primary tumor resection was classified as PTCT. We compared the progression-free survival (PFS) and overall survival (OS) of patients with and without PTCT.

Results: This study included 106 patients with a median age of 61.0 years, and of those, 42% were male and 73.6% were never-smokers. Exon 19 deletion was observed in 67.9%, 30.2% had a programmed cell death ligand 1 (PD-L1) tumor proportion score <1%, 33.0% had brain metastasis, and 40.6% had oligometastasis. In all, 53 (50%) patients underwent PTCT. Patients who underwent PTCT demonstrated significantly better PFS [30.3 (95% confidence interval (CI), 24.1-36.4) versus 18.2 (95% CI, 16.1-20.2) months; p = 0.005] and OS [not reached versus 36.7 (95% CI, 32.5-40.9) months; p = 0.005] than patients who did not. A multivariate analysis showed that PTCT was an independent factor associated with better PFS [hazard ratio (HR), 0.22; 95% CI, 0.10-0.49; p < 0.001] and OS [HR, 0.10; 95% CI, 0.01-0.82; p = 0.032]. The PFS benefits of PTCT were consistent across subgroups, and the HR tended to be lower in patients aged <65 years, males, smokers, stage IVB disease, L858R, PD-L1 expression ⩾1%, non-oligometastasis, and brain metastasis.

Conclusion: Of the patients with advanced EGFR-mutant LAD, those who underwent PTCT had a significantly better survival outcome than those who did not. The survival benefits were consistent across different subgroups.

Keywords: EGFR mutation; PD-L1; lung adenocarcinoma; osimertinib; primary tumor radiotherapy; primary tumor resection.