LAUSR

Background: Treatment options for patients with recurrent glioblastoma (rGBM) are limited. The lack of effectiveness from oral multi-targeted tyrosine kinase inhibitors, like sunitinib, might be due to a restricted blood-brain barrier penetration. We previously found that standard daily dosed sunitinib resulted in relatively low tumor drug concentrations in patients with GBM (PMID: 35165100). Based on these results, we here tested whether an alternatively scheduled, high-dose intermittent sunitinib treatment strategy with the aim to increase tumor drug concentrations, would improve the outcome of patients with rGBM compared to standard therapy with lomustine. Preliminary efficacy and safety results of the trial are presented. Methods: The STELLAR-trial is a randomized multicenter phase II/III clinical study for patients with rGBM (NCT03025893). Patients were randomized 1:1 to high-dose intermittent sunitinib (300mg once every week (Q1W) in part 1 or 700mg once every two weeks (Q2W) in part 2) or to standard therapy with lomustine (110mg/m2 once every 6 weeks). Adult patients with de novo or secondary glioblastoma with first recurrence after a maximum of one line of chemotherapy and ≥ 3 months since completion of radiotherapy were eligible. The primary endpoint of the trial was progression-free survival (PFS). Secondary endpoints included overall survival (OS), six-month progression-free survival (PFS6) and tolerability of the treatment. A pre-planned interim analysis for futility was performed after inclusion of 25% of patients in both part 1 and part 2. Results: At the pre-planned interim analysis, after inclusion of 26 and 29 patients in part 1 and 2, respectively, the trial was terminated for futility. The median PFS (mPFS) for sunitinib 300mg Q1W was 1.5 months (95% CI 1.4 - 1.7) as compared to 1.5 months (95% CI 1.4 - 1.6) for lomustine (HR 1.24, 95% CI 0.55 - 2.79; p=0.60). For sunitinib dosed at 700mg Q2W, the mPFS was 1.4 months (95% CI 1.3 - 1.5) as compared to 1.5 months (95% CI 1.3 - 1.7) for lomustine (HR 0.96, 95% CI 0.44 - 2.10; p=0.92). The median OS (mOS) for sunitinib 300 mg Q1W was 6.5 months (95% CI 4.5 - 8.5) compared to 4.7 (95% CI 3.3 - 6.0) for lomustine (log rank p=0.83). For sunitinib 700mg Q2W the mOS was 4.7 months (95% CI 3.8 - 5.6) compared to 6.8 months (95% CI 1.7 - 12.0) for lomustine (log rank p=0.65). The percentage of patients that were progression free at 6 months was 8% for both sunitinib groups and 15% for the lomustine group. In general, both treatment strategies with either high-dose intermittent sunitinib or lomustine were tolerated well with maximal grade 3 toxicities in respectively 8% and 15% of patients. Conclusion: Alternative high-dose intermittent sunitinib treatment failed to improve the outcome of patients with rGBM when compared to standard lomustine therapy. Since lomustine remains a poor treatment strategy in rGBM, novel, more effective therapies are urgently needed. Citation Format: Jorien B. Janssen, Cyrillo Brahm, Chantal M. Driessen, Janine Nuver, Mariette Labots, Mathilde C. Kouwenhoven, Esther S. Aliaga, Roelien H. Enting, Jan Cees de Groot, Johannes Berkhof, Annemiek M. Walenkamp, Henk M. Verheul, Myra E. van Linde. The STELLAR trial: A phase II/III study of high-dose intermittent sunitinib in patients with recurrent glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT139.