Anlotinib prolongs PFS in glioblastoma

Anlotinib, an anti-angiogenic tyrosine kinase inhibitor (TKI), has demonstrated a significant benefit in combination with the standard Stupp regimen for patients with newly diagnosed glioblastoma. Results from a randomised phase 2 trial showed that this combination significantly improves progression-free survival (PFS), although 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, previously showed encouraging results in a single-arm pilot study (NCT04119674) when added to the Stupp regimen. Its efficacy and safety were further evaluated in a double-blind, randomised phase 2 trial (NCT04959500).

This study randomised 153 participants with newly diagnosed glioblastoma, 4–6 weeks after surgery, 1:1 to receive either the Stupp regimen plus anlotinib or the Stupp regimen plus placebo. The primary endpoint was PFS; secondary endpoints were OS, objective response rate (ORR), and safety. Dr Yuanyuan Chen (Sun Yat-sen University Cancer Center, China) presented the findings [2].

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 ORR was also higher with 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,” said 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;352:987-996.
2. Chen Y, et al. Efficacy and safety of STUPP regimen with or without anlotinib for newly diagnosed glioblastoma: Results of a multicenter, double-blind, randomized phase II trial. LBA2000, ASCO Annual Meeting 2025, 30 May–3 June, Chicago, IL, USA.

Medical writing support was provided by Dr Marten Dooper.
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Posted on 5 June 20255 June 2025