Postoperative anlotinib plus radiotherapy in patients with newly diagnosed, unmethylated O6-methylguanine-DNA methyltransferase glioblastoma: A single-arm, phase 2 study.

Abstract / Summary

Patients with unmethylated O6-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. 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. 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. 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).

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