A phase II trial of anlotinib plus EGFR-TKIs in advanced non-small cell lung cancer with gradual, oligo, or potential progression after EGFR-TKIs treatment (CTONG-1803/ALTER-L001)

• Published in: Journal of hematology and oncology Vol. 18; no. 1; pp. 3 - 10
• Main Authors: Chen, Hua-Jun, Tu, Hai-Yan, Hu, Yanping, Fan, Yun, Wu, Guowu, Cang, Shundong, Yang, Yi, Yang, Nong, Ma, Rui, Jin, Gaowa, Xu, Ximing, Liu, Anwen, Tang, Shubin, Cheng, Ying, Yu, Yan, Xu, Chong-Rui, Zhou, Qing, Wu, Yi-Long
• Format: Journal Article
• Language: English
• Published: London BioMed Central 05.01.2025; BioMed Central Ltd; BMC
• Subjects: Adult; Aged; Anlotinib; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Blood vessels; Cancer Research; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Cell survival; Chemotherapy; Clinical medicine; Clinical trials; Disease control; Disease Progression; Drug dosages; EGFR mutation; Epidermal growth factor receptors; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; Female; Gradual progression; Hematology; Humans; Indoles - administration & dosage; Indoles - adverse effects; Indoles - therapeutic use; Kinases; Lung cancer; Lung cancer, Non-small cell; Lung cancer, Small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation; Non-small cell lung cancer; Non-small cell lung carcinoma; Oligo progression; Oncology; Oral administration; Patients; Pemetrexed; Product development; Progression-Free Survival; Protein Kinase Inhibitors - administration & dosage; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Quinolines - administration & dosage; Quinolines - adverse effects; Quinolines - therapeutic use; Response rates; Small cell lung carcinoma; Toxicity; Tumors; Tyrosine kinase inhibitors; Young Adult; China; EGFR mutation; Oligo progression; Anlotinib; Gradual progression; Non-small cell lung cancer
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-024-01656-0

Background The study is to evaluate the efficacy and safety of combined anlotinib and EGFR-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) who had gradual, oligo, or potential progression after previous EGFR-TKIs treatment. Methods We conducted an open-label, single-arm, multicenter, phase II trial in China. Eligible patients were 18–75 years old with histologically or cytologically confirmed NSCLC who were EGFR mutation positive and showed gradual, oligo, or potential progression after EGFR-TKIs. Anlotinib (12 mg/day) was administered orally for 2 weeks and then off 1 week in a 3-week cycle. EGFR-TKIs were continue used. The primary endpoint was progression-free survival (PFS). The secondary endpoints included 6- and 12-month PFS rate, objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results From July 2019 to December 2022, 120 patients were enrolled. The median PFS (mPFS) was 9.1 months (95% CI 6.8–11.7). The PFS rates at 6 and 12 months was 68.5% and 38.8% respectively. For 86 patients with first-line 1st /2nd generation EGFR-TKIs, the mPFS was 9.2 months (95% CI 6.7–12.6). For 32 patients with first-line 3rd generation EGFR-TKIs, the mPFS was 10.3 months (95% CI 6.1–13.3). Overall ORR and DCR were 6.7% (95% CI 2.9–12.7) and 87.5% (95% CI 80.2–92.8), respectively. 52.5% of patients had grade 3 or higher treatment-emergent adverse events (TEAEs). Conclusion Anlotinib in combination with continuation of EGFR-TKIs prolonged the clinical benefit of EGFR-TKIs, demonstrating favorable survival outcomes and manageable toxicity in NSCLC treated with EGFR-TKIs and had specific progression modes, such as gradual progression. Trial registration NCT04007835.