Phase II study of concurrent radiation therapy, temozolomide, and bevacizumab followed by bevacizumab/everolimus as first-line treatment for patients with glioblastoma.
OBJECTIVE
To evaluate the efficacy of adding bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, and everolimus, a mammalian target of rapamycin (mTOR inhibitor), to standard radiation therapy/temozolomide in the first-line treatment of patients with glioblastoma.


METHODS
Following surgical resection or biopsy, patients with newly diagnosed glioblastoma received standard radiation therapy/temozolomide plus bevacizumab 10 mg/kg intravenously (IV) every 2 weeks. Four weeks after the completion of radiation therapy, patients began oral everolimus 10 mg daily, and continued bevacizumab every 2 weeks; therapy continued until tumor progression or unacceptable toxicity.


RESULTS
Sixty-eight patients were treated, 82% of whom had previously undergone partial or complete surgical resection. Sixty-four patients completed combined modality therapy, and 57 patients began maintenance therapy with bevacizumab/everolimus. Thirty-one of 51 patients (61%) with measurable tumor had objective responses. After a median follow-up of 17 months, the median progression-free survival (PFS) was 11.3 months (95% confidence interval [CI], 9.3-13.1 months); median overall survival was 13.9 months. Toxicity was consistent with the known toxicity profile of bevacizumab; grade 3/4 toxicities during maintenance therapy related to everolimus included fatigue (27%), pneumonitis (7%), and stomatitis (5%).


CONCLUSIONS
The use of bevacizumab and everolimus as part of first-line combined modality therapy for glioblastoma was feasible and efficacious. The PFS compared favorably to previous reports with standard radiation therapy/temozolomide therapy, and is similar to results achieved in other phase II trials in which bevacizumab was added to fist-line treatment. Ongoing randomized phase III trials will clarify the role of bevacizumab in this setting.
Sarah Cannon Research Institute, Nashville, Tennessee 37203, USA. jhainsworth@tnonc.com
John D
JD
Hainsworth
Kent C
KC
Shih
Gregg C
GC
Shepard
Guy W
GW
Tillinghast
Brett T
BT
Brinker
David R
DR
Spigel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D000068338:Everolimus; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077204:Temozolomide; D055815:Young Adult
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D000068258:Bevacizumab; D003606:Dacarbazine; D000068338:Everolimus; D020123:Sirolimus; D000077204:Temozolomide