Phase II Study of Bortezomib in Combination with Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients with Newly-Diagnosed Glioblastoma Multiforme: Safety and Efficacy Assessment

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Xiao-Tang Kong, Nhung T. Nguyen, Yoon J. Choi, Guicheng Zhang, HuyTram N. Nguyen, Emese Filka, Stacey Green, William H. Yong, Linda M. Liau, Richard M. Green, Tania Kaprealian, Whitney B. Pope, P. Leia Nghiemphu, Tim Cloughesy, Andrew Lassman, Albert Lai
Purpose/ObjectiveTo assess the safety and efficacy of upfront treatment using bortezomib in combination with standard radiation therapy (RT) and temozolomide, followed by adjuvant bortezomib and temozolomide for up to 24 cycles in patients with newly-diagnosed glioblastoma multiforme (GBM).Patients and MethodsTwenty-four newly-diagnosed GBM patients were enrolled. Patients received standard external beam regional RT with concurrent temozolomide commencing 3-6 weeks after surgery, followed by adjuvant temozolomide and bortezomib for up to 24 cycles or until tumor progression. During RT, bortezomib was given at 1.3 mg/m² on days 1, 4, 8, 11, 29, 32, 36, and 39. Post RT, bortezomib was given at 1.3 mg/m² on days 1, 4, 8, and 11 every 4 weeks.ResultsNo unexpected adverse events occurred from the addition of bortezomib. Efficacy analysis showed median progression free survival (PFS) of 6.2 months (95% CI, 3.7-8.8) with promising PFS rates at 18 months and beyond compared to historical norms (25.0% at 18 and 24 months, 16.7% at 30 months). In terms of overall survival (OS), the median OS was 19.1 months (95% CI, 6.7-31.4) with improved OS rates at 12 months and beyond (87.5% at 12, 50.0% at 24, 34.1% at 36 throughout 60 months) compared to historical norms. Median PFS was 24.7 months (95% CI 8.5-41.0) in 10 MGMT methylated and 5.1 months (95% CI 3.9-6.2) in 13 unmethylated patients. The estimated median OS was 61 months in the methylated (the upper bound of 95% CI could not be reached) and 16.4 months (95% CI 11.8-21.0) in the unmethylated patients.ConclusionAddition of bortezomib to current standard radio-chemotherapy in newly-diagnosed GBM patients was tolerable. The PFS and OS rates appeared promising with more benefit to MGMT methylated patients. Further clinical investigation is warranted in a larger cohort of patients.

Teaser

We conducted a phase II study of bortezomib in combination with temozolomide and regional radiotherapy (RT) in 24 newly-diagnosed GBM patients. Addition of bortezomib to current standard care was well-tolerated, and observed toxicities were acceptable. Overall survival rates were improved compared to historical norms, especially in MGMT methylated patients. Further clinical investigation is warranted in larger cohort of patients.


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