Factors associated with outcomes of second-line treatment for EGFR-mutant non-small-cell lung cancer patients after progression on first- or second-generation EGFR-tyrosine kinase inhibitor treatment

Cheng-Yu Chang; Chung-Yu Chen; Shih-Chieh Chang; Ching-Yi Chen; Yi-Chun Lai; Chun-Fu Chang; Yu-Feng Wei

doi:10.3389/fonc.2023.1104098

Factors associated with outcomes of second-line treatment for EGFR-mutant non-small-cell lung cancer patients after progression on first- or second-generation EGFR-tyrosine kinase inhibitor treatment

Front Oncol. 2023 Jun 20:13:1104098. doi: 10.3389/fonc.2023.1104098. eCollection 2023.

Authors

Cheng-Yu Chang^{1

2}, Chung-Yu Chen^{3

4}, Shih-Chieh Chang^{5

6

7}, Ching-Yi Chen⁸, Yi-Chun Lai^{5

6}, Chun-Fu Chang^{5

6}, Yu-Feng Wei^{9

10}

Affiliations

¹ Division of Chest Medicine, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
² Nursing Department, Cardinal Tien Junior College of Healthcare and Management, New Taipei City, Taiwan.
³ Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Douliou, Taiwan.
⁴ College of Medicine, National Taiwan University, Taipei, Taiwan.
⁵ Division of Chest Medicine, Department of Internal Medicine, National Yang-Ming Chiao Tung University Hospital, Yi-Lan, Taiwan.
⁶ Faculty of Medicine, College of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
⁷ Department of Critical Care Medicine, National Yang-Ming Chiao Tung University Hospital, Yi-Lan, Taiwan.
⁸ Division of Chest Medicine, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan.
⁹ School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan.
¹⁰ Department of Internal Medicine, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan.

Abstract

Purpose: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutant non-small-cell lung cancer (NSCLC) patients. However, factors associated with outcomes after progression on first-line therapy are seldom investigated.

Materials and methods: From January 2016 to December 2020, we enrolled 242 EGFR-mutant stage IIIB-IV NSCLC patients who progressed on first- or second-generation EGFR-TKI treatments, and 206 of them receive second-line treatments after disease progression. The factors that predict the survival outcomes of different second-line treatments after disease progression were evaluated. Clinical and demographic characteristics, including metastatic sites, neutrophil-to-lymphocyte ratio (NLR) at first-line progression, and second-line treatment regimens, and whether re-biopsied after disease progression or not, were reviewed for outcome analysis.

Results: The univariate analysis showed that the PFS was shorted in male patients (p =0.049), patients with ECOG performance state ≥ 2 (p =0.014), former smokers (p =0.003), patients with brain metastasis (p =0.04), second-line chemotherapy or EGFR-TKIs other than osimertinib (p =0.002), and NLR ≥5.0 (p=0.024). In addition, second-line osimertinib was associated with longer OS compared to chemotherapy and other EGFR-TKI treatment (p =0.001). In the multivariate analysis, only second-line osimertinib was an independent predictor of PFS (p =0.023). Re-biopsy after first-line treatment was associated with a trend of better OS. Patients with NLR ≥5.0 at disease progression had shorter OS than patients with NLR <5.0 (p = 0.008).

Conclusion: The benefits of osimertinib necessitate that aggressive re-biopsy after progression on first- or second-generation EGFR-TKI treatment is merited for appropriate second-line treatments to provide better outcomes for these patients.

Keywords: epidermal growth factor receptor-tyrosine kinase inhibitor; neutrophil-to-lymphocyte ratio; non-small-cell lung cancer; osimertinib; re-biopsy; second-line.