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已发表论文
EGFR 突变 NSCLC 奥希替尼耐药后紫杉类药物与培美曲塞的比较：一项含两种体外模型验证的回顾性队列研究
Authors Yang N, Wan N , Guo Y, Xiong L, Chen X, Du D, Xie B , Zhou J
Received 3 September 2025
Accepted for publication 30 December 2025
Published 13 January 2026 Volume 2026:18 564913
DOI https://doi.org/10.2147/CMAR.S564913
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Harikrishna Nakshatri
Ning Yang,1,* Ning Wan,2,3,* Ya Guo,2,3 Lijuan Xiong,4 Xiting Chen,4 Dou Du,4 Bo Xie,1,4 Juan Zhou1,4
1Department of Oncology, General Hospital of Southern Theater Command, Guangzhou, People’s Republic of China; 2Department of Clinical Pharmacy, General Hospital of Southern Theater Command, Guangzhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 4Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Juan Zhou, Department of Oncology, General Hospital of Southern Theater Command, No. 111 Liuhua Road, Guangzhou, 510010, People’s Republic of China, Tel +86 20 88686608, Email juanzhn@163.com Bo Xie, Department of Oncology, General Hospital of Southern Theater Command, No. 111 Liuhua Road, Guangzhou, 510010, People’s Republic of China, Tel +86 20 88686606, Email xiebodoctor@163.com
Purpose: To evaluate whether chemotherapy backbone selection influences outcomes in epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) after acquired resistance to osimertinib, addressing the absence of a preferred post osimertinib chemotherapy approach.
Methods: Outcomes were retrospectively compared between taxane based and pemetrexed based chemotherapy using propensity score matching and multivariable Cox models; progression was stratified as gradual or dramatic. An exploratory in vitro assay compared chemosensitivity between osimertinib resistant sublines and parental cells.
Results: After 1:1 matching, taxanes showed numerically longer progression free survival (PFS; median 8.8 vs 7.9 months; hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.48– 1.03) and overall survival (OS; 18.8 vs 15.9 months; HR: 0.70, 95% CI: 0.45– 1.09) versus pemetrexed, without statistical significance. In the gradual progression cohort, outcomes were comparable. By contrast, in the dramatic progression cohort, taxanes were associated with longer PFS (7.7 vs 6.4 months; HR: 0.51, 95% CI: 0.30– 0.86; P=0.009) and OS (16.1 vs 12.7 months; HR: 0.54, 95% CI: 0.30– 0.97; P=0.034). Multivariable analysis identified taxanes as an independent favorable factor in dramatic progression for PFS (adjusted hazard ratio [aHR]: 0.48, 95% CI: 0.27– 0.84; P=0.011) and OS (aHR: 0.51, 95% CI: 0.27– 0.96; P=0.036). Non hematologic toxicities were more frequent with taxanes than pemetrexed (56/74, 75.7% vs 52/95, 54.7%). Additionally, osimertinib resistant sublines exhibited reduced half-maximal inhibitory concentration (IC50) to taxanes versus parental cells (P< 0.05).
Conclusion: Taxane based chemotherapy was associated with more favorable outcomes than pemetrexed in dramatic progression after osimertinib resistance, with higher non hematologic toxicity. These findings, supported by exploratory in vitro sensitivity, warrant prospective validation.
Keywords: osimertinib, acquired resistance, NSCLC, EGFR, chemosensitivity
1Department of Oncology, General Hospital of Southern Theater Command, Guangzhou, People’s Republic of China; 2Department of Clinical Pharmacy, General Hospital of Southern Theater Command, Guangzhou, People’s Republic of China; 3School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 4Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Juan Zhou, Department of Oncology, General Hospital of Southern Theater Command, No. 111 Liuhua Road, Guangzhou, 510010, People’s Republic of China, Tel +86 20 88686608, Email juanzhn@163.com Bo Xie, Department of Oncology, General Hospital of Southern Theater Command, No. 111 Liuhua Road, Guangzhou, 510010, People’s Republic of China, Tel +86 20 88686606, Email xiebodoctor@163.com
Purpose: To evaluate whether chemotherapy backbone selection influences outcomes in epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) after acquired resistance to osimertinib, addressing the absence of a preferred post osimertinib chemotherapy approach.
Methods: Outcomes were retrospectively compared between taxane based and pemetrexed based chemotherapy using propensity score matching and multivariable Cox models; progression was stratified as gradual or dramatic. An exploratory in vitro assay compared chemosensitivity between osimertinib resistant sublines and parental cells.
Results: After 1:1 matching, taxanes showed numerically longer progression free survival (PFS; median 8.8 vs 7.9 months; hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.48– 1.03) and overall survival (OS; 18.8 vs 15.9 months; HR: 0.70, 95% CI: 0.45– 1.09) versus pemetrexed, without statistical significance. In the gradual progression cohort, outcomes were comparable. By contrast, in the dramatic progression cohort, taxanes were associated with longer PFS (7.7 vs 6.4 months; HR: 0.51, 95% CI: 0.30– 0.86; P=0.009) and OS (16.1 vs 12.7 months; HR: 0.54, 95% CI: 0.30– 0.97; P=0.034). Multivariable analysis identified taxanes as an independent favorable factor in dramatic progression for PFS (adjusted hazard ratio [aHR]: 0.48, 95% CI: 0.27– 0.84; P=0.011) and OS (aHR: 0.51, 95% CI: 0.27– 0.96; P=0.036). Non hematologic toxicities were more frequent with taxanes than pemetrexed (56/74, 75.7% vs 52/95, 54.7%). Additionally, osimertinib resistant sublines exhibited reduced half-maximal inhibitory concentration (IC50) to taxanes versus parental cells (P< 0.05).
Conclusion: Taxane based chemotherapy was associated with more favorable outcomes than pemetrexed in dramatic progression after osimertinib resistance, with higher non hematologic toxicity. These findings, supported by exploratory in vitro sensitivity, warrant prospective validation.
Keywords: osimertinib, acquired resistance, NSCLC, EGFR, chemosensitivity