2499 - Efficacy and Safety of STUPP Regimen ± Anlotinib for Newly Diagnosed Glioblastoma: A Multicenter, Double-Blind, Randomized Phase II Trial

Y. Chen¹, G. Liu², P. Sun³, M. Li⁴, X. Yang⁵, L. Pan⁶, L. Wang⁷, Y. Hua⁸, M. Zhao⁹, Y. Liu¹⁰, J. Ran¹¹, H. Cai¹², X. LU¹³, J. Hao¹⁴, X. Li¹⁵, W. Zheng¹⁶, Z. Liu¹⁷, S. Lin¹⁸, M. Deng¹⁹, Q. Yang²⁰, C. Guo²⁰, J. Li²¹, and Z. Chen²²; ¹State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China., Guangzhou, China, ²The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China, ³Lanzhou University Second Hospital, Lanzhou, China, ⁴The First Affiliated Hospital of Nanchang University, Nanchang, China, ⁵Internet Hospital of Tianjin Medical University General Hospital, Tianjin, China, ⁶Chinese PLA General Hospital & Medical Academy, Beijing, China, ⁷Tangdu Hospital, Shanxi, China, ⁸Department of Radiation Oncology, Zhejiang Cancer Hospital, Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, China, ⁹Henan Cancer Hospital, Zhengzhou, Henan, China, ¹⁰West China Hospital, Sichuan University, Chengdu, China, ¹¹The First Hospital of Lanzhou University, Lanzhou, China, ¹²Gansu Provincial Hospital, Lanzhou, China, ¹³Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, ¹⁴The First Affiliated Hospital of Bengbu Medical College, Bengbu, China, ¹⁵Shenzhen peoples Hospital, Shenzhen, China, ¹⁶The Sixth Medical Center of PLA General Hospital, Beijing, China, ¹⁷Radiotherapy department, Cancer center, The Tenth Affiliated Hospital, Southern Medical University(Dongguan People’s Hospital), Dongguan, Guangdong, China, ¹⁸Beijing Tiantan Hospital, Capital Medical University, Beijing, China, ¹⁹State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China, ²⁰Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China, ²¹Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine; Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, China, ²²Department of Neurosurgery/Neuro-oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China

Purpose/Objective(s): Postoperative radiotherapy with concurrent temozolomide (TMZ) followed by up to six cycles of adjuvant TMZ chemotherapy, known as the STUPP regimen, is the established standard treatment for newly diagnosed glioblastoma (GBM). However, its effectiveness is limited. Anlotinib, a multi-kinase inhibitor that targets tumor angiogenesis and cell proliferation, has shown promising results in preclinical GBM models and phase I clinical trials. To assess the efficacy and safety of combining the STUPP regimen with anlotinib, we designed and conducted a phase II trial to evaluate the efficacy and safety of combining the STUPP regimen with anlotinib (NCT 04959500). Materials/

Methods: This is a multicenter, double-blind, randomized, placebo-controlled trial with an expected 150 patients randomly assigned 1:1 ratio to receive TMZ-based radiochemotherapy with anlotinib or placebo. Eligibility criteria include histologically confirmed GBM, ECOG performance score =2, age =18 years, and lack of significant comorbidity. The primary endpoint is median progression-free survival (PFS), while secondary endpoints include 1-year overall survival rate, PFS at 6 months, overall response rate, duration of response, disease control rate, quality of life, and toxicity.
Results: From July 2021 to January 25th, 2024, 153 patients were enrolled. The results in this abstract were all obtained without exposing the blind state. The median PFS was 10.05 months (95% CI, 9.43-11.89) in the overall patient population, while the predicted mPFS of placebo group was 7 months according to the results of STUPP and AVAGlio trials. The 1-year overall survival rate is 75.45% (95% CI, 67.06%-81.98%), and the 2-year overall survival rate is 39.41% (95% CI, 26.42%-52.13%). 24.8% of patients experienced at least one grade 3 or higher treatment-related adverse events. 9.8% of patients experienced serious treatment-related adverse events. The most frequent TRAEs were lymphocytopenia, thrombocytopenia, leukopenia, decreased neutrophil count.
Conclusion: Under the condition of data blinding, the current research findings suggest that the combination of anlotinib with the STUPP regimen demonstrates encouraging therapeutic efficacy and favorable tolerability, indicating its potential as a viable treatment modality.