TIPS-11 EFFICACY AND SAFETY OF STUPP REGIMEN WITH OR WITHOUT ANLOTINIB FOR NEWLY DIAGNOSED GLIOBLASTOMA: INTERIM RESULTS OF A MULTICENTER, DOUBLEBLIND, RANDOMIZED PHASE II TRIAL

Abstract

Abstract BACKGROUND Postoperative radiotherapy with concomitant temozolomide (TMZ) followed by ≤ six cycles of adjuvant TMZ chemotherapy (STUPP regimen) is the standard treatment for newly diagnosed glioblastoma (GBM) with limited effectiveness. Anlotinib inhibits both tumor angiogenesis and tumor cell proliferation by targeting multiple kinases, and showing promising results in preclinical GBM models and phase I clinical trials. We designed a phase II trial to verify the efficacy and safety of the STUPP regimen plus anlotinib (NCT 04959500). 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. Major eligibility criteria include histologically confirmed newly diagnosed GBM and an ECOG performance score ≤2. Other criteria for inclusion include age ≥18 years and lack of significant comorbidity. The primary endpoint is the median progression-free survival (PFS). 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 February 8th 2023, 147 patients were enrolled. The results in this abstract were all obtained without exposing the blind state. The median PFS was 9.9 months (95% CI, 9.5-11.9) in the overall patient population, while the predicted mPFS of placebo group was 7 months according to the results of STUPP and AVAGlio trials. Grade 1 (72.82%) and grade 2 (24.27%) adverse events (AEs) were mainly observed, while grade 3 or worse AEs accounted for 2.9% among all AEs. The most frequent TRAEs were lymphocytopenia, decreased platelet count, decreased white blood cell count, decreased neutrophil count and hypertension. Two death cases occurred due to COVID-19 and severe pneumonia. CONCLUSIONS Under the condition of data blinding, these interim results suggest that the STUPP regimen with anlotinib demonstrate potential promising efficacy and a tolerable safety.