Phase II study of bevacizumab plus erlotinib for recurrent malignant gliomas.
2045 Background: Bevacizumab (B), a neutralizing VEGF monoclonal antibody, has anti-glioma activity as single agent and in combination with cytotoxic therapy. Erlotinib (E), an EGFR tyrosine kinase inhibitor, may exhibit anti-tumor activity in some malignant glioma (MG) patients. B plus E was associated with clinical benefit in several solid tumors. We performed a single-arm, phase II study to evaluate the efficacy of B and E in patients with recurrent MG. METHODS: The primary endpoint was 6-month progression-free survival (PFS-6). Radiographic response, pharmacokinetics and correlative biomarkers were secondary endpoints. E was orally administered daily at 200 mg/day for patients not on enzyme-inducing anticonvulsants (EIAC) and 500 mg/day for patients on EIAC. All patients received 10 mg/kg of B intravenously every two weeks. Key eligibility criteria included: age ≥ 18 years; KPS ≥ 60; > 4 weeks from prior surgery, XRT or chemotherapy. Patients with either > 3 prior progressions, requirement for therapeutic anti-coagulation or acute hemorrhage on pre-treatment imaging were excluded. RESULTS: Fifty-six patients with recurrent MG (n = 24 for glioblastoma multiforme [GBM] and n = 32 for anaplastic gliomas [AGs]) were assessable for outcome. The PFS-6 rates were 25% for GBM and 50% for AGs. There was no survival difference between EIAC and non-EIAC groups. Rash (54% grade 1-2 and 38% grade 3) was the most common side effect. Nausea, diarrhea, and fatigue were common but mostly grade 1-2. Serious side effects were rare and included two patients with pulmonary embolism, single patients with either intestinal perforation, ischemic stroke, gastric bleeding, or nasal septal perforation. Pharmacokinetic and tissue biomarker profiles are in preparation. CONCLUSIONS: Among heavily pretreated recurrent MG patients, bevacizumab plus erlotinib is tolerated and associated with encouraging anti-tumor benefit. No significant financial relationships to disclose.
Sathornsumetee, S; Desjardins, A; Vredenburgh, JJ; Rich, JN; Gururangan, S; Friedman, AH; Friedman, HS; Reardon, DA
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