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New molecular entity: Everolimus (Afinitor), an antineoplastic agent, was approved on March 30, 2009, for the treatment of advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib
Everolimus is an antineoplastic agent that inhibits mammalian target of rapamycin (mTOR), thus reducing cell proliferation, angiogenesis, and glucose uptake. This agent was approved on March 30, 2009, for the treatment of patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib.
Efficacy. Everolimus was evaluated in an international, multicenter, randomized, double-blind trial that compared everolimus 10 mg/d with placebo; both everolimus and placebo were used in combination with best supportive care. A total of 416 patients whose disease had progressed despite treatment with sunitinib, sorafenib, or both were randomized 2:1 to treatment with everolimus or placebo. Progression-free survival (PFS) was assessed via a blinded, independent radiologic review. Everolimus-treated patients had a median PFS of 4.9 months (95% CI, 4–5.5) versus 1.9 months (95% CI, 1.8–1.9) among placebo-treated patients (HR=0.33; 95% CI, 0.25–0.43; P<.001). Overall survival results were not mature.
Safety. Everolimus may be associated with noninfectious pneumonitis, which is a class effect of rapamycin derivatives. Some fatal cases have been observed. Signs and symptoms may include hypoxia, pleural effusion, cough, or dyspnea. This agent has immunosuppressive properties and thus may predispose patients to contraction of infectious diseases, especially infections caused by opportunistic pathogens. Some reported cases of infection have been severe or fatal. Patients treated with everolimus have reported the development of mouth ulcers, stomatitis, and oral mucositis. Everolimus-treated patients should not receive live vaccines and should avoid close contact with others who have received live vaccines. This agent may cause fetal harm in pregnant women. The most common adverse events associated with everolimus treatment include stomatitis, infections, asthenia, fatigue, cough, and diarrhea.