Real-world analysis of survival outcomes in advanced EGFR-mutant NSCLC patients treated with platinum-pemetrexed after EGFR-TKI treatment failure

Introduction: EGFR tyrosine kinase inhibitors (TKIs) are the standard therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations in the first-line setting. Despite initial efficacy, resistance to EGFR-TKIs often develops, and platinum-based chemotherapy is the predominant...

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Main Authors: Zong-Han Yao, Wei-Yu Liao, Chin-Yao Yang, Chao-Chi Ho, Jin-Yuan Shih, Kuan-Yu Chen, James Chih-Hsin Yang, Chong-Jen Yu
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Journal of the Formosan Medical Association
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Online Access:http://www.sciencedirect.com/science/article/pii/S0929664624003851
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author Zong-Han Yao
Wei-Yu Liao
Chin-Yao Yang
Chao-Chi Ho
Jin-Yuan Shih
Kuan-Yu Chen
James Chih-Hsin Yang
Chong-Jen Yu
author_facet Zong-Han Yao
Wei-Yu Liao
Chin-Yao Yang
Chao-Chi Ho
Jin-Yuan Shih
Kuan-Yu Chen
James Chih-Hsin Yang
Chong-Jen Yu
author_sort Zong-Han Yao
collection DOAJ
description Introduction: EGFR tyrosine kinase inhibitors (TKIs) are the standard therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations in the first-line setting. Despite initial efficacy, resistance to EGFR-TKIs often develops, and platinum-based chemotherapy is the predominant subsequent treatment. For this study, we aimed to identify prognostic factors for overall survival (OS) and progression-free survival (PFS) among advanced EGFR-mutant NSCLC patients receiving platinum-pemetrexed after progression on EGFR-TKIs. Our analysis specifically focuses on 1st-line treatments limited to 1st- or 2nd-generation EGFR-TKIs, while not restricting later-line treatments involving osimertinib prior to chemotherapy. Materials and methods: From 2012 to 2017, 363 patients who received first-line treatment with first- or second-generation EGFR-TKIs, including gefitinib, erlotinib, and afatinib were enrolled. Some patients received different EGFR-TKIs, including osimertinib, as later-line treatment before platinum-pemetrexed. Results: Median OS from the initiation of platinum-pemetrexed was 22.0 months and median PFS with platinum-pemetrexed was 6.2 months. In the multivariate Cox model, we identified three independent prognostic factors for better OS: postoperative recurrence (HR: 0.34, p = 0.004), first-line EGFR-TKI PFS ≥12 months (HR: 0.54, p = 0.002), and osimertinib treatment after platinum-pemetrexed (HR: 0.56, p = 0.005) while BMI <18.5 indicated poor prognosis (HR:1.76, p = 0.049). No statistically significant independent prognostic factors for PFS were found. Receiving osimertinib before platinum-pemetrexed treatment did not impact PFS with platinum-pemetrexed treatment (HR: 1.11, p = 0.64). Conclusion: Postoperative recurrence, first-line EGFR-TKI PFS ≥12 months and osimertinib treatment after platinum-pemetrexed predicted better OS, while BMI <18.5 predicted worse OS. Osimertinib treatment before platinum-pemetrexed treatment did not affect the efficacy of platinum-pemetrexed.
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spelling doaj-art-db2edf82fad24113999645cf174a15f22025-08-20T03:56:41ZengElsevierJournal of the Formosan Medical Association0929-66462025-08-01124875976610.1016/j.jfma.2024.08.017Real-world analysis of survival outcomes in advanced EGFR-mutant NSCLC patients treated with platinum-pemetrexed after EGFR-TKI treatment failureZong-Han Yao0Wei-Yu Liao1Chin-Yao Yang2Chao-Chi Ho3Jin-Yuan Shih4Kuan-Yu Chen5James Chih-Hsin Yang6Chong-Jen Yu7Department of Internal Medicine, National Taiwan University Cancer Center and National Taiwan University College of Medicine, Taipei, Taiwan; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, TaiwanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Corresponding author. Department of Internal Medicine, National Taiwan University Hospital, # 7, Chung-Shan South Rd, Taipei, 100, ROC, Taiwan.Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, TaiwanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, TaiwanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, TaiwanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, TaiwanDepartment of Oncology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Oncology, National Taiwan University Cancer Center and National Taiwan University College of Medicine, Taipei, TaiwanDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu County, TaiwanIntroduction: EGFR tyrosine kinase inhibitors (TKIs) are the standard therapy for non-small-cell lung cancer (NSCLC) patients with EGFR-activating mutations in the first-line setting. Despite initial efficacy, resistance to EGFR-TKIs often develops, and platinum-based chemotherapy is the predominant subsequent treatment. For this study, we aimed to identify prognostic factors for overall survival (OS) and progression-free survival (PFS) among advanced EGFR-mutant NSCLC patients receiving platinum-pemetrexed after progression on EGFR-TKIs. Our analysis specifically focuses on 1st-line treatments limited to 1st- or 2nd-generation EGFR-TKIs, while not restricting later-line treatments involving osimertinib prior to chemotherapy. Materials and methods: From 2012 to 2017, 363 patients who received first-line treatment with first- or second-generation EGFR-TKIs, including gefitinib, erlotinib, and afatinib were enrolled. Some patients received different EGFR-TKIs, including osimertinib, as later-line treatment before platinum-pemetrexed. Results: Median OS from the initiation of platinum-pemetrexed was 22.0 months and median PFS with platinum-pemetrexed was 6.2 months. In the multivariate Cox model, we identified three independent prognostic factors for better OS: postoperative recurrence (HR: 0.34, p = 0.004), first-line EGFR-TKI PFS ≥12 months (HR: 0.54, p = 0.002), and osimertinib treatment after platinum-pemetrexed (HR: 0.56, p = 0.005) while BMI <18.5 indicated poor prognosis (HR:1.76, p = 0.049). No statistically significant independent prognostic factors for PFS were found. Receiving osimertinib before platinum-pemetrexed treatment did not impact PFS with platinum-pemetrexed treatment (HR: 1.11, p = 0.64). Conclusion: Postoperative recurrence, first-line EGFR-TKI PFS ≥12 months and osimertinib treatment after platinum-pemetrexed predicted better OS, while BMI <18.5 predicted worse OS. Osimertinib treatment before platinum-pemetrexed treatment did not affect the efficacy of platinum-pemetrexed.http://www.sciencedirect.com/science/article/pii/S0929664624003851Non-small cell lung cancerEpidermal growth factor receptorTyrosine kinase inhibitorsPlatinum doubletPemetrexed
spellingShingle Zong-Han Yao
Wei-Yu Liao
Chin-Yao Yang
Chao-Chi Ho
Jin-Yuan Shih
Kuan-Yu Chen
James Chih-Hsin Yang
Chong-Jen Yu
Real-world analysis of survival outcomes in advanced EGFR-mutant NSCLC patients treated with platinum-pemetrexed after EGFR-TKI treatment failure
Journal of the Formosan Medical Association
Non-small cell lung cancer
Epidermal growth factor receptor
Tyrosine kinase inhibitors
Platinum doublet
Pemetrexed
title Real-world analysis of survival outcomes in advanced EGFR-mutant NSCLC patients treated with platinum-pemetrexed after EGFR-TKI treatment failure
title_full Real-world analysis of survival outcomes in advanced EGFR-mutant NSCLC patients treated with platinum-pemetrexed after EGFR-TKI treatment failure
title_fullStr Real-world analysis of survival outcomes in advanced EGFR-mutant NSCLC patients treated with platinum-pemetrexed after EGFR-TKI treatment failure
title_full_unstemmed Real-world analysis of survival outcomes in advanced EGFR-mutant NSCLC patients treated with platinum-pemetrexed after EGFR-TKI treatment failure
title_short Real-world analysis of survival outcomes in advanced EGFR-mutant NSCLC patients treated with platinum-pemetrexed after EGFR-TKI treatment failure
title_sort real world analysis of survival outcomes in advanced egfr mutant nsclc patients treated with platinum pemetrexed after egfr tki treatment failure
topic Non-small cell lung cancer
Epidermal growth factor receptor
Tyrosine kinase inhibitors
Platinum doublet
Pemetrexed
url http://www.sciencedirect.com/science/article/pii/S0929664624003851
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