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Drug warning issued for bevacizumab/sunitinib combo
This month, Genentech notified health care professionals of several incidences of microangiopathic hemolytic anemia in patients with solid tumors taking bevacizumab in combination with sunitinib malate.
The drug warning is a result of phase-1 trial data presented at a poster session at the 2008 ASCO Annual Meeting in May. The trial explored the use of bevacizumab (Avastin, Genentech) in combination with sunitinib malate, a combination that is neither approved nor recommended.
The study included 25 patients who were divided into three cohorts. Researchers employed a fixed dose of bevacizumab (10 mg/kg/IV every two weeks) and an escalating dose of sunitinib malate (25 mg, 37.5 mg and 50 mg daily on a four week on, two week off schedule).
According to the company’s warning letter issued in July, five of 12 patients at the highest sunitinib dose had microangiopathic hemolytic anemia. Two of the cases were considered severe and showed evidence of thrombocytopenia, anemia, reticulocytosis, reductions in serum haptoglobin and schistocytes on peripheral smear, among others.
Within three weeks of discontinuing both drugs, effects in both severe cases were reversible.
As a result of the phase-1 data, a similar phase-2 trial of sunitinib (50 mg) plus or minus bevacizumab with a similar dosing schedule was closed.
Although no events of microangiopathic hemolytic anemia were reported in two additional randomized, phase-2 trials of bevacizumab plus sunitinib and chemotherapy, poor tolerability due to myelosuppression, fatigue and gastrointestinal complications caused them to close.
Genentech urged health care professionals to report any cases of microangiopathic hemolytic anemia or adverse events caused by bevacizumab to them or the FDA’s MedWatch system. – by Stacey L. Adams
For more information:
- Feldman DR. Phase I trial of bevacizumab plus sunitinib in patients with metastatic renal cell carcinoma. #5100. Presented at: 2008 ASCO Annual Meeting; May 30-June 3, 2008; Chicago.