Combination of anlotinib and irinotecan as second-line therapy in extensive-stage small-cell lung cancer relapsed within six months: a single-arm phase Ⅱ study

Minna Zhang; Yi Tang; Jiafeng Liang; Lucheng Zhu; Bing Wang; Kaicheng Pan; Xiao Xu; Xueqin Chen; Bing Xia

doi:10.1016/j.lungcan.2025.108630

Combination of anlotinib and irinotecan as second-line therapy in extensive-stage small-cell lung cancer relapsed within six months: a single-arm phase Ⅱ study

Lung Cancer. 2025 Jun 20:205:108630. doi: 10.1016/j.lungcan.2025.108630. Online ahead of print.

Authors

Minna Zhang¹, Yi Tang¹, Jiafeng Liang¹, Lucheng Zhu¹, Bing Wang¹, Kaicheng Pan¹, Xiao Xu¹, Xueqin Chen², Bing Xia³

Affiliations

¹ Department of Thoracic Oncology, Hangzhou Cancer Hospital, Hangzhou 310002, China.
² Department of Thoracic Oncology, Hangzhou Cancer Hospital, Hangzhou 310002, China; Department of Medical Oncology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University. Hangzhou 310006, China; Fourth Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou 310053, China. Electronic address: chenxueqin@hospital.westlake.edu.cn.
³ Department of Thoracic Oncology, Hangzhou Cancer Hospital, Hangzhou 310002, China. Electronic address: xiabing@hospital.westlake.edu.cn.

PMID: 40555062
DOI: 10.1016/j.lungcan.2025.108630

Abstract

Purpose: There is still no satisfactory treatment strategy for patients with extensive-stage small-cell lung cancer (ES-SCLC) relapsed within 6 months after first-line treatment.

Patients and methods: Subjects received 12 mg oral anlotinib on days 1-14 and irinotecan (65 mg/m²) on day 1 and 8 every 3 weeks (up to 4 cycles), followed by anlotinib maintainance therapy with anlotinib alone. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS) and safety.

Results: Thirty-seven patients were evaluable for efficacy and safety profile. ORR was 62.2 % (23/37) and DCR was 91.9 % (34/37). Median PFS and OS for all the patients were 4.5 and 7.2 months. PFS and OS of patients with a 3 < chemothrerapy-free survival (CTFI) ≤ 6 months were better than those of patients with a CTFI ≤ 3 months (PFS 6.5 vs 3.9 months, P = 0.0073; OS 18.5 vs 5.9 months, P < 0.001). Patients who previously received chemotherapy alone or chemotherapy combined with immunotherapy as first-line treatment had similar median PFS and OS (mPFS 4.4 vs 4.9 months, P = 0.38; mOS 7.2 vs 8.3 months, P = 0.79). Only three patients (8.5 %) suffered from Grade 3 adverse effects, which were thrombocytopenia, leukopenia, and anemia.

Conclusion: The combination of anlotinib and irinotecan as second-line treatment for ES-SCLC patients who relapsed within 6 months demonstrated promising efficacy and had manageable toxicities. Patients with 3 < CTFI ≤ 6 months had longer PFS and OS than those with CTFI ≤ 3 months. Previous immunotherapy did not affect the efficacy of subsequent anlotinib and irinotecan. It may become a novel therapeutic strategy for this population. The trial was registered with www.

Clinicaltrials: gov (No. NCT04757779).

Keywords: Anlotinib; ES-SCLC; Efficacy; Irinotecan; Safety.

Associated data

ClinicalTrials.gov/NCT04757779