Anlotinib plus Temozolomide for Recurrent Glioma: A Single-Center, Retrospective Study of 30 cases

Abstract Objective To determine the efficacy and tolerability of Anlotinib plus temozolomide (TMZ) as a first-line treatment for recurrent malignant glioma (rMG). Methods A total of 30 eligible patients who relapsed from the standard chemoradiotherapy regimen (TMZ and radiotherapy) or had macroscopic residual tumor after surgery because of tumor located in the eloquent brain areas were enrolled in this study between March 2018 and January 2021. Patients were subjected to a concurrent treatment of Anlotinib (12mg qd, 14 days on with 7 days off) and TMZ (200mg/m2, 5 days on with 23 days off) until disease progression or intolerable toxicity. Efficacy was evaluated using Response Assessment in Neuro-Oncology(RANO) criteria for high-grade glioma. Safety was assessed using NCI-CTCAE 4.0. Survival was estimated with the Kaplan-Meier curve and log-rank test. Results Until April 2023, our median follow-up time was 28.1 ± 5.07 months(95% CI:18.20-38.06m). The median OS(from recurrence to death or end of follow-up) was 17.87 ± 4.29 m(95%CI: 9.46-26.28m). 1-year, 1.5 year, 2-year OS rates were were 60.0%, 46.7% and 36.7% respectively. The median PFS(from the treatment of Anlotinib and TMZ to the endpoint) was 7.83 ± 0.82m(95%CI, 6.22-9.44m). 6-month, 1-year PFS rates were 63.3%, 36.7%, respectively. In the univariate analysis, patients of WHO Ⅱ group have a longer mOS and mPFS than that of WHO Ⅲ and Ⅳ group(Ⅱ: 30.45 ± 4.32m, Ⅲ: 15.07 ± 5.72m, Ⅳ: 9.21 ± 1.90m, P = 0.035). Patients ≤ 55 had a longer mPFS compared with those > 55 years old(12.97 ± 1.71m vs. 7.33 ± 1.95m. p = 0.010), but failed to reach statistical difference in OS(19.90 ± 6.29m vs. 10.53 ± 1.68m, p = 0.106). While their gender, 1p/19q and IDH mutation are not independent negative predictors on OS or PFS. In the multivariate analysis, age, pathological grade and IDH mutation all failed to serve as an independent negative predictor of PFS or OS in recurrent glioma. Conclusion Anlotinib combined with TMZ was effective for recurrent glioma in terms of OS and PFS, and was well tolerated in patients. Further randomized controlled clinical studies are needed to confirm the efficacy of Anlotinib combined with TMZ for the treatment of rMG.