Anlotinib prolongs progression-free survival in glioblastoma

Anlotinib, an anti-angiogenic tyrosine kinase inhibitor (TKI), has demonstrated a significant progression-free survival (PFS) benefit in combination with the standard Stupp regimen for participants with newly diagnosed glioblastoma. A significant overall survival (OS) benefit was observed only in a molecularly defined subgroup.

For almost 2 decades, the Stupp regimen (radiotherapy plus temozolomide) has remained the standard-of-care for newly diagnosed glioblastoma; yet, prognosis continues to be poor [1]. Angiogenesis is a hallmark of glioblastoma; thus, targeting this pathway represents a logical therapeutic approach. Anlotinib, a multi-targeted TKI, has previously demonstrated encouraging results in a single-arm pilot study (NCT04119674) when added to the Stupp regimen. The current double-blind, randomised phase 2 trial (NCT04959500), presented by Dr Yuanyuan Chen (Sun Yat-sen University Cancer Center, China), further evaluated anlotinib’s efficacy and safety [2].

This study randomised 153 participants with newly diagnosed glioblastoma and 4–6 weeks after surgery to receive either the Stupp regimen plus anlotinib or the Stupp regimen plus placebo in a 1:1 ratio. The primary endpoint was PFS; secondary endpoints were OS, objective response rate, and safety.

Median PFS was significantly longer in the anlotinib arm than in the placebo arm: 9.89 months versus 5.85 months (HR 0.59; 95% CI 0.42–0.85; P=0.0018). The objective response rate was also higher in the arm receiving anlotinib (16.7% vs 5.3%; P=0.022). However, the OS benefit was limited to the subgroup of 49 participants with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation (HR 0.31; 95% CI 0.12–0.79; P=0.0093).

The most frequent grade ≥3 adverse events in the anlotinib versus placebo arms were thrombocytopenia (7.79% vs 1.32%), neutropenia (6.49% vs 3.95%), lymphopenia (6.49% vs 7.89%), leukopenia (6.49% vs 2.63%), and hypertension (5.19% vs 0%).

“The observed benefit in PFS, along with manageable toxicity, supports the potential of the Stupp-anlotinib combination as a novel therapeutic strategy for newly diagnosed glioblastoma,” elaborated Dr Chen. She noted that the improved OS seen in the MGMT-methylated subgroup warrants further validation in a larger, prospective cohort.

1. Stupp R, et al. N Eng J Med. 2005;352(10):987-996.
2. Chen Y, et al. Efficacy and safety of STUPP regime with or without anlotinib for newly diagnosed glioblastoma: result of a multicenter, double blind, randomised phase II trial. Abstract LBA2000, ASCO Annual Meeting 2025, May 30–June 3, Chicago, IL, USA.

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Posted on 30 July 2025