Anlotinib as third- or further-line therapy for short-term relapsed small-cell lung cancer: subgroup analysis of a randomized phase 2 study (ALTER1202)

Abstract

Patients with small-cell lung cancer (SCLC) relapse within months after completing previous therapies. This study aimed to investigate the efficacy and safety of anlotinib as third- or further-line therapy in patients with short-term relapsed SCLC from ALTER1202. Patients with short-term relapsed SCLC (disease progression within 3 months after completing ≥ two lines of chemotherapy) in the anlotinib (n = 67) and placebo (n = 34) groups were analyzed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, objective response rate (ORR), disease control rate, and safety. Anlotinib significantly improved median PFS/OS (4.0 vs. 0.7 months, P < 0.0001)/(7.3 vs. 4.4 months, P = 0.006) compared with placebo. The ORR was 4.5%/2.9% in the anlotinib/placebo group (P = 1.000). The DCR in the anlotinib group was higher than that in the placebo group (73.1% vs. 11.8%, P < 0.001). The most common adverse events (AEs) were hypertension (38.8%), loss of appetite (28.4%), and fatigue (22.4%) in the anlotinib group and gamma-glutamyl transpeptidase elevation (20.6%) in the placebo group. No grade 5 AEs occurred. For patients with short-term relapsed SCLC, third- or further-line anlotinib treatment was associated with improved survival benefit. Further studies are warranted in this regard.

Keywords

anlotinib / chemotherapy / short-term relapsed / small-cell lung cancer

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Acknowledgements

The authors wish to thank all the participating patients and their families, study personnel at all sites, and the ALTER 1202 clinical trial team. This study was supported by the Jilin Provincial Health and Family Planning Commission (No. 2019J077), the Science and Technology Agency of Jilin Provincial Project (No. 20200201518JC), and Chia-tai Tianqing Pharmaceutical Group Co., Ltd. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethics guidelines

Jianhua Shi, Ying Cheng, Qiming Wang, Kai Li, Lin Wu, Baohui Han, Gongyan Chen, Jianxing He, Jie Wang, Haifeng Qin, and Xiaoling Li declare that they have no conflict of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.

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