KEY TAKEAWAYS
- The PAZOGLIO phase I/II trial aimed to assess the safety and efficacy of PZB with TMZ in GBM maintenance per Stupp protocol.
- Results showed the feasibility of adding PZB to TMZ in the Stupp protocol for resected GBM; phase II enrollment is ongoing.
Pazopanib (PZB), an anti-angiogenic tyrosine kinase inhibitor, demonstrates efficacy in recurrent advanced glioblastomas (GBM)—data advocate for investigating PZB in early-stage brain cancer.
Esma B. Saada and the team conducted a study using the Stupp protocol to assess the safety (phase I) and effectiveness (phase II) of combining PZB with Temozolomide(TMZ) during the maintenance phase following complete or partial resection surgery in GBM patients.
The PAZOGLIO trial was a prospective phase I clinical trial with a 3+3 design carried out at 3 French centers from 2015 to 2022. Investigations were conducted on the four predetermined PZB dosage levels (200 mg, 400 mg, 600 mg, and 800 mg).
During the first two cycles, dose-limiting toxicity (DLT) was assessed. The dose at which a given percentage of patients (2 out of 3 or 2 out of 6) suffered DLT was determined to be the maximum tolerated dose (MTD). Dose escalation ceased upon reaching the MTD, and the recommended phase II dose (RP2D) was determined as the lower level dose of the MTD.
About 20 patients were enrolled, with a median age of 54 years (range: 25 to 69). Among them, 14 of 20 (70%) were women, and 15 of 20 (75%) had undergone complete resection. The 1-year overall survival (OS) and progression-free survival (PFS) rates were 71% [52-96] and 42% [25-72], respectively. Additionally, the median OS and PFS were 22 months (95%CI [16.7-NA]) and 9.5 months (95%CI [6.4-NA]), respectively.
Approximately 328 treatment-related adverse events (TRAEs) were observed, consisting of 203 grade 1 (62%), 102 grade 2 (31%), and 23 grade 3 (7%) events. No severe hemorrhage, healing issues, or treatment-related deaths occurred. About 3 patients of 20 (15%) experienced DLT: 1 patient (12.5%) at a dose level of 600 mg (grade 2 thrombocytopenia) and 2 patients (33.5%) at a dose level of 800 mg (grade 3 thrombocytopenia and hypertension). A statistically significant increase in terms of AUC0-24h (P=0.005), AUC0-8h (P=0.013), and Cmax (P=0.008) between Cycle 1 and Cycle 2 was observed.
The study concluded that adding PZB to TMZ in the Stupp protocol is viable for resected GBM patients. The recommended phase II dose was 600 mg PZB daily with TMZ during maintenance. Phase II enrollment is ongoing.
The trial was sponsored by Centre Antoine Lacassagne.
Source: https://cslide.ctimeetingtech.com/tat2024/attendee/confcal/show/session/6
Clinical Trial: https://clinicaltrials.gov/study/NCT02331498
Saada EB, Gal J, Frenel JS, et al. (2024) “Phase I/II study of pazopanib and temozolomide in patients with newly diagnosed glioblastoma multiforme: PAZOGLIO trial.” presented at ESMO-TAT 2024 (62P).
