Postoperative anlotinib plus radiotherapy in patients with newly diagnosed, unmethylated O ⁶ ‐methylguanine–DNA methyltransferase glioblastoma: A single‐arm, phase 2 study

BACKGROUND: -methylguanine-DNA methyltransferase (MGMT) glioblastoma derive minimal benefit from the standard temozolomide chemoradiotherapy, leaving an urgent need for more effective therapies. The objective of this phase 2 study was to evaluate the efficacy of anlotinib plus radiotherapy in this disease. METHODS: In this single-arm, phase 2 study, patients with newly diagnosed, unmethylated MGMT glioblastoma were recruited after surgical resection. Patients received standard radiotherapy (60.0 grays) and concomitant with anlotinib (12 mg once daily, 2 weeks on/1 week off), followed by six cycles of anlotinib maintenance. The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), OS rates at 12 and 24 months, PFS rates at 6 and 12 months, and safety. RESULTS: Between October 12, 2020, and August 1, 2022, 32 patients were enrolled and received protocol therapy, and all were evaluable for efficacy and safety analyses. At a median follow-up of 18.6 months (range, 8.3-50.3 months), the median OS was 19.1 months (95% confidence interval, 14.4-22.4 months), with 12-month and 24-month OS rates of 90.6% and 30.0%, respectively. The median OS did not reach the prespecified threshold of 20.1 months. The median PFS was 11.1 months (95% confidence interval, 9.6-12.9 months), with 6-month and 12-month PFS rates of 96.9% and 37.5%, respectively. Four patients (12.5%) experienced grade 3 or worse treatment-related adverse events, two of which (6.3%) were serious. No treatment-related deaths occurred. CONCLUSIONS: Postoperative anlotinib plus radiotherapy demonstrated clinically meaningful activity with a manageable safety profile in patients with unmethylated MGMT glioblastoma (Chinese Clinical Trials Registry identifier: ChiCTR2000040116).