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Temsirolimus, bevacizumab shows promise for pancreatic neuroendocrine tumors
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Combination treatment with temsirolimus and bevacizumab demonstrated considerable activity and a reasonable safety profile in patients with progressive pancreatic neuroendocrine tumors, according to results of a phase 2 trial.
Pancreatic neuroendocrine tumors (PNETs) are rare tumors located within the endocrine cells, and few effective therapies are available, according to background information provided by researchers.
Timothy J. Hobday, MD, assistant professor of oncology at Mayo Clinic in Rochester, Minn., and colleagues conducted a trial to determine how these tumors responded to the combination of the mTOR inhibitor temsirolimus (Torisel, Wyeth Pharmaceuticals) and the VEGF-A monoclonal antibody bevacizumab (Avastin, Genentech).
Fifty-eight patients with progressive PNETs were enrolled in the two-stage, single-arm trial, and 56 patients were eligible for response assessment.
Patients received temsirolimus 25 mg intravenously once a week, and bevacizumab 10 mg/kg administered intravenously once every 2 weeks. Treatment continued until disease progression, significant toxicity or patient refusal.
Twenty-three patients (41%) demonstrated a response, far exceeding the response rate observed with single targeted agents in patients with progressive PNETs, Hobday and colleagues wrote. Researchers reported 6-month PFS of 79%, median PFS of 13.2 months (95% CI, 11.2-16.6) and median OS of months (95% CI, 27.1-not reached).
The most common grade 3 or grade 4 adverse events reported by evaluable patients included hypertension (21%), fatigue (16%), lymphopenia (14%) and hyperglycemia (14%).
“We await future clinical trial results of combined mTOR and VEGF therapies in PNETS, as well as results of our single-agent bevacizumab trial in PNETs,” they wrote. “But it seems this biologic combination may become an important addition to systemic therapy for PNETs.”
Disclosure: The researchers report research funding from, honoraria from, and consultant or advisory roles with Genentech, Novartis, Pfizer and Roche.
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