Osimertinib plus anlotinib for advanced NSCLC with acquired EGFR T790M mutation: results from a multicenter phase II study with ctDNA analysis

被引：0

作者：

Xinyue Wang ^{[1
]}

Zhaona Li ^{[2
]}

Liuchun Wang ^{[1
]}

Yan Liang ^{[1
]}

Chun Huang ^{[1
]}

Peng Chen ^{[1
]}

Dingzhi Huang ^{[1
]}

Xia Song ^{[3
]}

Cuimin Ding ^{[4
]}

Changli Wang ^{[5
]}

Richeng Jiang ^{[1
]}

机构：

[1] Department of Thoracic Oncology, Tianjin Lung Cancer Center, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute & Hospita

[2] Department of Oncology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou

[3] Department of Respiratory Medicine, Shanxi Provincial Cancer Hospital, Taiyuan

[4] Department of Respiratory Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang

[5] Department of Lung Cancer, Tianjin Lung Cancer Center, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute & Hospital, Tia

[6] Center for Precision Cancer Medicine & Translational Research, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute & Hospi

来源：

BMC Medicine | / 23卷 / 1期

基金：

中国国家自然科学基金;

关键词：

Anlotinib; CtDNA; EGFR T790M mutation; Non-small cell lung cancer; Osimertinib;

D O I：

10.1186/s12916-025-04044-8

中图分类号：

学科分类号：

摘要：

Background: Osimertinib is a standard treatment for first- or second-line therapy in patients with non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFR). However, options are limited for patients with acquired EGFR T790M mutations resistant to first- or second-generation EGFR-tyrosine kinase inhibitors (TKIs). This study assessed the efficacy and safety of combining osimertinib with anlotinib in this patient population and explored circulating tumor DNA (ctDNA) as a biomarker of treatment outcomes. Methods: In this prospective, single-arm, phase II trial, 31 patients with advanced NSCLC resistant to prior first- or second-generation EGFR-TKIs therapy received osimertinib (80 mg daily) and anlotinib (12 mg daily on days 1–14 of each 21-day cycle). Efficacy endpoints included progression-free survival (PFS) and overall survival (OS). ctDNA was analyzed using next-generation sequencing (NGS) to monitor mutation status and treatment response. Results: The median PFS was 16.2 months (95% confidence interval [CI] 9.8–23.6, 90% CI 14.2–20.9), and the median OS was 31.4 months (95% CI 27.3–not reached). The objective response rate (ORR) was 45.2% (95% CI 30.6–66.6%), with a disease control rate (DCR) of 96.8% (95% CI 86.3–100.0%). ctDNA analysis showed that activating EGFR mutation clearance after two treatment cycles correlated with significantly longer PFS and OS. The regimen was well-tolerated, with no grade 4 or higher adverse events observed. Conclusions: Osimertinib combined with anlotinib demonstrates promising long-term efficacy and manageable safety in EGFR T790M-positive NSCLC. Clearance of ctDNA, particularly of EGFR mutations, could serve as a valuable predictive biomarker, supporting the implementation of personalized treatment strategies. Trial registration: ClinicalTrials.gov, NCT04029350. © The Author(s) 2025.

引用

共 36 条

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