CHEMOTHERAPY-BASED VERSUS TARGET-BASED TREATMENT FOR PATIENTS WITH EGFR-MUTATED NON-SMALL CELL LUNG CANCER WHO PROGRESSED ON FIRST-LINE TKIS THERAPY: A TARGET TRIAL EMULATION IN CHINA
Author(s)
ZHIHAO XU1, TAO XU, Dr2, JIALONG TAN, Prof3, JIAN WANG, Prof3, Lazaros Andronis, Prof4, Chao Tang, Dr5, Tongtong Huang, Dr5, Shangyang Luan, Dr6, Jiaxin Guo, Dr6, Xinyi Tao, Dr6, Jason Madan, Prof4, kuixu Lan, Dr5;
1Dong Furen Institute of Economic and Social Development, Wuhan University, PhD student, Wuhan, China, 2Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China, 3Dong Fureng Institute of Economic and Social Development, Wuhan University, Wuhan, China, 4Centre for Health Economics at Warwick, University of Warwick, Coventry, United Kingdom, 5The Affiliated Hospital of Qingdao University, Qingdao, China, 6Qingdao medical college of Qingdao university, Qingdao, China
1Dong Furen Institute of Economic and Social Development, Wuhan University, PhD student, Wuhan, China, 2Department of Pulmonary and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China, 3Dong Fureng Institute of Economic and Social Development, Wuhan University, Wuhan, China, 4Centre for Health Economics at Warwick, University of Warwick, Coventry, United Kingdom, 5The Affiliated Hospital of Qingdao University, Qingdao, China, 6Qingdao medical college of Qingdao university, Qingdao, China
OBJECTIVES: Optimal second-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC) after first-line EGFR-TKI failure is influenced by the patient’s underlying genetic resistance mechanisms. Limited data exist on the benefits of continued targeted therapy versus chemotherapy for on-target or off-target patients in real-world settings.
METHODS: Target trial emulation and inverse probability of censoring weighting (IPCW) were used to reduce selection bias and adjust for censoring. Patients received second-line treatment with either chemotherapy-based therapy (CBT) or target-based therapy (TBT), following standard clinical protocols and individualized according to each patient’s genetic and clinical profile. The primary outcome was progression-free survival (PFS). Hazard ratios (HRs) for disease progression were estimated using IPCW-adjusted Cox proportional hazards models.
RESULTS: A total of 333 patients were analyzed: 241 in the on-target group and 92 in the off-target group, defined by genetic profiling. In the on-target subgroup, median PFS was 13.6 months for CBT (n=40) and 13.2 months for TBT (n=201), with an IPCW-adjusted HR of 0.25 (95% CI, 0.09-0.65; P<0.05). In the off-target subgroup, median PFS was 7.3 months for CBT (n=45) and 10.5 months for TBT (n=47), with an HR of 0.29 (95% CI, 0.12-0.72; P<0.05). Sensitivity analyses, including unadjusted models, propensity score matching, analyses without censoring, and placebo tests, confirmed the robustness of these findings. Overall, TBT was associated with a significantly lower risk of disease progression compared with CBT in both subgroups.
CONCLUSIONS: In patients with EGFR-mutated NSCLC after first-line TKI failure, target-based therapy (TBT) was associated with a significantly lower risk of disease progression than chemotherapy-based therapy (CBT). This effect was still evident in the off-target subgroup with driver gene-negative resistance mechanisms. These findings help fill a critical gap in existing research on both on-target and off-target populations and highlight the importance of real-world evidence in optimizing post-progression treatment strategies.
METHODS: Target trial emulation and inverse probability of censoring weighting (IPCW) were used to reduce selection bias and adjust for censoring. Patients received second-line treatment with either chemotherapy-based therapy (CBT) or target-based therapy (TBT), following standard clinical protocols and individualized according to each patient’s genetic and clinical profile. The primary outcome was progression-free survival (PFS). Hazard ratios (HRs) for disease progression were estimated using IPCW-adjusted Cox proportional hazards models.
RESULTS: A total of 333 patients were analyzed: 241 in the on-target group and 92 in the off-target group, defined by genetic profiling. In the on-target subgroup, median PFS was 13.6 months for CBT (n=40) and 13.2 months for TBT (n=201), with an IPCW-adjusted HR of 0.25 (95% CI, 0.09-0.65; P<0.05). In the off-target subgroup, median PFS was 7.3 months for CBT (n=45) and 10.5 months for TBT (n=47), with an HR of 0.29 (95% CI, 0.12-0.72; P<0.05). Sensitivity analyses, including unadjusted models, propensity score matching, analyses without censoring, and placebo tests, confirmed the robustness of these findings. Overall, TBT was associated with a significantly lower risk of disease progression compared with CBT in both subgroups.
CONCLUSIONS: In patients with EGFR-mutated NSCLC after first-line TKI failure, target-based therapy (TBT) was associated with a significantly lower risk of disease progression than chemotherapy-based therapy (CBT). This effect was still evident in the off-target subgroup with driver gene-negative resistance mechanisms. These findings help fill a critical gap in existing research on both on-target and off-target populations and highlight the importance of real-world evidence in optimizing post-progression treatment strategies.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO109
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Oncology