Starting Patients on Afinitor

Afinitor is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib.

Please see Important Safety Information.

When should your patients start therapy with Afinitor®?1

According to National Comprehensive Cancer Network (NCCN) guidelines, Afinitor is the first and only category 1 treatment option after VEGFR tyrosine kinase inhibitor (TKI) failure. Start them on the only daily oral therapy approved as a second line therapy after sunitinib or sorafenib failure in advanced renal cell carcinoma.

What kind of response could your patients expect with Afinitor?2,3

Clinical trials have shown that people receiving Afinitor as a second-line therapy after sunitinib or sorafenib failure in advanced renal cell carcinoma have experienced a clear therapeutic benefit. While results may vary, the treatment effect was similar across prognostic scores and prior sorafenib and/or sunitinib treatment. Learn more about the clinical trial design.

What Are the Serious Risks Associated with Afinitor?

Afinitor can cause lung and breathing problems. In some patients, lung or breathing problems may be severe, and can even lead to death. Patients should contact their physician immediately if they experience new or worsening cough, shortness of breath, difficulty breathing, or wheezing.

Afinitor can make the patient more likely to have an infection, such as pneumonia, or a bacterial, fungal or viral infection, Viral infections may include active hepatitis B in people who have had hepatitis B in the past (reactivation). In some people these infections may be severe, and can even lead to death, including reactivation of hepatitis B in patients who have had hepatitis B in the past. Patients should contact their physician immediately if they have a fever of 100.5°F or above, chills, or do not feel well. Symptoms of hepatitis B or infection may included fever, skin rash, joint pain and inflammation, tiredness, loss of appetite, nausea, pale stool or dark urine, yellowing of the skin, and pain in the upper right side.

AFINITOR may cause kidney failure. In some people this may be severe and can even lead to death. Patients should have tests to check their kidney function before and during their treatment with AFINITOR.

AFINITOR can cause mouth ulcers and sores. Patients should tell their healthcare provider if they have pain, discomfort, or open sores in their mouth. Their healthcare provider may tell them to use a special mouthwash or mouth gel that does not contain alcohol or peroxide.

Dosage of Afinitor may need to be lowered or stopped for awhile. In clinical trials, some patients treated with Afinitor had serious side effects. Learn ways to help manage side effects.

How is Afinitor thought to work?2

Afinitor is a signal transduction inhibitor targeting mTOR (mammalian target of rapamycin). This means that Afinitor works by directly inhibiting mTOR.* This has been shown to result in reduced tumor cell growth and proliferation, reduced cell metabolism, and reduced tumor angiogenesis. Inhibition of mTOR by Afinitor has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies. See how Afinitor works.

How long should your patients be on therapy with Afinitor?

Patients should remain on Afinitor for as long as their doctor recommends continuing treatment. Afinitor should most likely be continued until a doctor determines that the cancer has grown larger or spread, or until the risks of taking Afinitor outweigh the benefits. Find more information on recommended dosing and administration.

What is the recommended dose of Afinitor?

The recommended dose of Afinitor for treatment of advanced renal cell carcinoma is 10 mg, to be taken once daily at the same time every day, either consistently with or consistently without food. Afinitor tablets should be swallowed whole with a glass of water. No dose adjustments are necessary for age, body weight, or renal function.

Management of severe and/or intolerable adverse reactions may require temporary dose reduction and/or interruption of Afinitor therapy. If dose reduction is required, the suggested dose is 5 mg daily. Find more information on recommended
dosing and administration.

Afinitor should not be used in patients with Child-Pugh class C hepatic impairment. Exposure of everolimus was increased in patients with moderate hepatic impairment. For patients with Child-Pugh class B hepatic impairment, reduce dose to 5 mg daily.

Avoid co-administration with strong CYP3A4 and/or PgP inhibitors. Use caution and reduce the Afinitor dose to 2.5 mg daily if co-administration with moderate CYP3A4 or PgP inhibitors is required. Avoid co-administration with strong CYP3A4 inducers; however, if co-administration is required, increase the Afinitor dose.

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References
  • National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Kidney Cancer. V.1.2010. http://www.nccn.org/professionals/physician_gls/
    PDF/kidney.pdf. Accessed September 30, 2009.
  • Afinitor [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2011.
  • Motzer RJ, Escudier B, Oudard S, et al; for the RECORD-1 Study Group. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer. 2010;116:4256-4265.

AFINITOR is indicated for the treatment of patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib.

Important Safety Information

AFINITOR is contraindicated in patients with hypersensitivity to everolimus, to other rapamycin derivatives, or to any of the excipients.

Non-infectious Pneumonitis: Non-infectious pneumonitis was reported in 11-14% of patients treated with Afinitor. The incidence of Common Terminology Criteria (CTC) grade 3 and 4 non-infectious pneumonitis was 1.6%-4.0% and 0.1%, respectively. Fatal outcomes have been observed. If symptoms are moderate, patients should be managed with dose interruption until symptoms improve. If symptoms are severe, AFINITOR therapy should be discontinued. Under both circumstances, corticosteroids may be indicated and AFINITOR may be reintroduced at 5 mg daily depending on the individual clinical circumstances. The development of pneumonitis has been reported even at a reduced dose.

Infections: AFINITOR has immunosuppressive properties and may predispose patients to localized or systemic bacterial, fungal, viral, or protozoal infections (including those with opportunistic pathogens). Viral infections may include reactivation of hepatitis B infection. Some of these infections have been severe (e.g., leading to respiratory or hepatic failure) or fatal. Physicians and patients should be aware of the increased risk of infection with Afinitor. Treatment of pre-existing invasive fungal infections should be completed prior to starting treatment. Be vigilant for signs and symptoms of infection and institute appropriate treatment promptly; interruption or discontinuation of AFINITOR should be considered. Discontinue AFINITOR if invasive systemic fungal infection is diagnosed and institute appropriate treatment.

Oral Ulceration: Oral ulcerations (i.e., mouth ulcers, stomatitis, and oral mucositis) are the most frequently occurring adverse event and occur in approximately 70% of advanced PNET patients, 44% of advanced RCC patients, and 86% of SEGA patients, which were mostly Grade 1 or 2. Grade 3 or 4 stomatitis was reported in 6% of patients with neuroendocrine tumors. In such cases, topical treatments are recommended, but alcohol- or peroxide-containing mouthwashes should be avoided. Antifungal agents should not be used unless fungal infection has been diagnosed.

Renal Failure: Cases of renal failure (including acute renal failure), some with a fatal outcome, have been observed in patients treated with AFINITOR.

Laboratory Tests and Monitoring: Elevations of serum creatinine, proteinuria, glucose, lipids, and triglycerides, and reductions of hemoglobin, lymphocytes, neutrophils, and platelets have been reported. Renal function, blood glucose, lipids, and hematologic parameters should be evaluated prior to treatment and periodically thereafter. When possible, optimal glucose and lipid control should be achieved before starting a patient on AFINITOR.

Drug-drug Interactions: Avoid co-administration with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole). Use caution and reduce the AFINITOR dose to 2.5 mg daily if co-administration with a moderate CYP3A4 and/or PgP inhibitor is required (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem). Avoid co-administration with strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital); however, if co-administration is required, increase the AFINITOR dose from 10 mg daily up to 20 mg daily, using 5 mg increments.

Hepatic Impairment: AFINITOR should not be used in patients with severe hepatic impairment. Exposure of everolimus was increased in patients with moderate hepatic impairment. AFINITOR dose should be reduced to 5 mg daily for patients with moderate hepatic impairment.

Vaccinations: The use of live vaccines and close contact with those who have received live vaccines should be avoided during treatment with AFINITOR.

Use in Pregnancy: Fetal harm can occur if AFINITOR is administered to a pregnant woman. Women of childbearing potential should be advised to use an effective method of contraception while using AFINITOR and for up to 8 weeks after ending treatment.

Adverse Reactions: The most common adverse reactions (incidence ≥30%) were stomatitis (44%), infections (37%), asthenia (33%), fatigue (31%), cough (30%), and diarrhea (30%). The most common grade 3/4 adverse reactions (incidence ≥5%) were infections (10%), dyspnea (7%), stomatitis (5%) and fatigue (5%). Deaths due to acute respiratory failure (0.7%), infection (0.7%), and acute renal failure (0.4%) were observed on the AFINITOR arm.

Laboratory Abnormalities: The most common laboratory abnormalities (incidence ≥ 50%, all grades) were: decreased hemoglobin (92%) and lymphocytes (51%); increased cholesterol (77%), triglycerides (73%), glucose (57%) and creatinine (50%). The most common grade 3/4 laboratory abnormalities (incidence ≥ 5%) were: decreased hemoglobin (13%), lymphocytes (18%), and phosphate (6%); and increased glucose (16%).

Please see full Prescribing Information for AFINITOR.