Third-line or above anlotinib in relapsed and refractory small cell lung cancer patients with brain metastases: A post hoc analysis of ALTER1202, a randomized, double-blind phase 2 study

Abstract

Background

The prognosis of patients with small cell lung cancer (SCLC) and brain metastases (BM) was poor. This study aimed to explore the efficacy and safety of anlotinib as third-line or above treatment in SCLC with BM.

Methods

This was a subgroup analysis of the ALTER1202 trial, which was a randomized, placebo-controlled trial aimed to evaluate the role of anlotinib as third-line treatment or above in patients with SCLC. This study included patients with BM at baseline. The efficacy and safety outcomes included progression-free survival (PFS), overall survival (OS), central nervous system (CNS), objective response rate (ORR), CNS disease control rate (DCR), time to CNS progression, and adverse events (AEs).

Results

Twenty-one and nine patients with BM were included in the anlotinib and placebo groups, respectively. The median PFS and OS were 3.8 months (95% confidence interval [CI]: 1.8–6.1) and 6.1 months (95% CI: 4.1–8.0) in the anlotinib group. Anlotinib was associated with a significant improvement in PFS (hazard ratio [HR] = 0.15, 95% CI: 0.04–0.51, p = 0.0005) and OS (HR = 0.26, 95% CI: 0.09–0.73, p = 0.0061) than placebo. Anlotinib significantly prolonged the time to CNS progression (p < 0.0001). The anlotinib group had a higher CNS DCR than placebo (95.2% vs. 22.2%, p = 0.0001). The most common grade 3 or higher AEs were increased lipase (19.0%), hypertension (14.3%), and hyponatremia (14.3%) in the anlotinib group.

Conclusions

Anlotinib proved to have potential CNS activity and a manageable toxicity profile in patients with SCLC and BM, significantly delaying CNS progression.