Indication

AFINITOR® (everolimus) Tablets is indicated for the treatment of adults 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, other rapamycin derivatives, or any excipients. 

Noninfectious pneumonitis was reported in up to 19% of patients...

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Oncology Nurse Center

The AFINITOR Nurse Center

Nurse

Nurses play a key role in the care and treatment of patients.

The AFINITOR Nurse Center is designed with this fact in mind. It is intended for educational purposes only and is not meant to replace the advice of a health care provider. Browse through the pages of this site to learn more about starting patients on AFINITOR, dosing and administration, tracking patients' treatment, addressing side effects, and more.

 

 

What AFINITOR Treats

Indications for AFINITOR

Oncology indications for AFINITOR include treatment of:

  • Postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole.
  • Adults with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced, or metastatic disease. AFINITOR is not indicated for the treatment of patients with functional carcinoid tumors.
  • Adults with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib.

aRCC
Advanced RCC (aRCC) is a progressive form of kidney cancer that begins in the lining of the renal tubules of the kidney.1
The Phase III, placebo-controlled RECORD-1 trial compared the once-daily oral mammalian target of rapamycin (mTOR) inhibitor AFINITOR to placebo in patients with aRCC who had failed previous treatment with Sutent® (sunitinib) and/or Nexavar® (sorafenib). RECORD-1 showed that median progression-free survival was 4.9 months (95% CI: 4.0 to 5.5) with AFINITOR vs 1.9 months (95% CI: 1.8 to 1.9) with placebo (HR 0.33; 95% CI: 0.25-0.43; P<0.0001), a 67% reduction in risk of progression.2,3

Important Safety Information
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%).
Please see additional Important Safety Information at the bottom of this page.
Please see full Prescribing Information.

Advanced Breast Cancer
The phase 3 BOLERO-2 trial evaluated AFINITOR plus exemestane vs placebo plus exemestane in a randomized, double-blind, multicenter study conducted in 724 postmenopausal women with estrogen receptor-positive, HER 2/neu-negative advanced breast cancer with recurrence or progression following prior therapy with letrozole or anastrozole. Median PFS was 7.8 months with AFINITOR plus exemestane [95% CI, 6.9-8.5] vs 3.2 months [95% CI, 2.8-4.1] with placebo plus exemestane (HR=0.45 [95% CI, 0.38-0.54]; P<0.0001) per local investigator assessment. The results of the PFS analysis based on independent central radiological assessment were consistent with the investigator assessment. PFS results were also consistent across the subgroups of age, race, presence and extent of visceral metastases, and sensitivity to prior hormonal therapy.2 

Important Safety Information
Adverse Reactions: The most common adverse reactions (incidence ≥30%) were stomatitis (67%), infections (50%), rash (39%), fatigue (36%), diarrhea (33%), and decreased appetite (30%). The most common Grade 3/4 adverse reactions (incidence ≥2%) were stomatitis (8%), infections (5%), hyperglycemia (5%), fatigue (4%), dyspnea (4%), pneumonitis (4%), and diarrhea (2%).
Please see additional Important Safety Information at the bottom of the Breast Cancer page.
Please see full Prescribing Information.

Advanced PNET
The placebo-controlled RADIANT-3 trial evaluated the safety and efficacy of AFINITOR in patients with advanced PNET. Data show median progression-free survival of 11 months (95% CI: 8.4 to 13.9) in patients on AFINITOR, compared with 4.6 months (95% CI: 3.1 to 5.4) in patients on placebo (HR 0.35; 95% Cl: 0.27-0.45; P<0.001). Investigator-determined response rate was low (4.8%) in the AFINITOR arm and there were no complete responses. Overall survival was not statistically significantly different between study arms [HR=0.94 (95% CI 0.73 to 1.20); P=0.30].2

Important Safety Information
Adverse Reactions: The most common adverse reactions (incidence ≥30%) were stomatitis (70%), rash (59%), diarrhea (50%), fatigue (45%), edema (39%), abdominal pain (36%), nausea (32%), fever (31%), headache (30%), and decreased appetite (30%). The most common grade 3/4 adverse reactions (incidence ≥5%) were stomatitis (7%) and diarrhea (5.5%). Deaths primarily due to adverse events during the double-blind treatment phase occurred in 7 patients taking AFINITOR.
Please see additional Important Safety Information at the bottom of the Advanced PNET page.
Please see the full Prescribing Information.

Getting Started

Getting Your Patients Started on the Once-Daily Oral mTOR Inhibitor, AFINITOR® (everolimus) Tablets

For Patients With aRCC
What can patients with aRCC expect if prescribed AFINITOR?

  • Clinical trials in patients with aRCC have shown that people receiving AFINITOR after sunitinib or sorafenib failure have experienced a therapeutic benefit. Treatment effect was similar across prognostic scores and prior sunitinib and/or sorafenib treatment.2 Find out more about the efficacy of AFINITOR in aRCC
  • Patients taking AFINITOR for aRCC should be monitored for adverse reactions.2 Find out more about safety
  • AFINITOR is taken orally, once a day.2 Find out more about the recommended dosing and administration

Important Safety Information
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%).
Please see additional Important Safety Information at the bottom of this page.
Please see full Prescribing Information.

For Patients With Advanced Breast Cancer
What can patients with advanced breast cancer expect if prescribed AFINITOR?

  • AFINITOR plus exemestane more than doubles median PFS over exemestane monotherapy2
  • Patients taking AFINITOR for advanced breast cancer should be monitored for adverse reactions.2 Find out more about safety and tolerability
  • AFINITOR is taken orally, once a day.2 Find out about the recommended dosing and administration

Important Safety Information
Adverse Reactions: The most common adverse reactions (incidence ≥30%) were stomatitis (67%), infections (50%), rash (39%), fatigue (36%), diarrhea (33%), and decreased appetite (30%). The most common Grade 3/4 adverse reactions (incidence ≥2%) were stomatitis (8%), infections (5%), hyperglycemia (5%), fatigue (4%), dyspnea (4%), pneumonitis (4%), and diarrhea (2%).
Please see additional Important Safety Information at the bottom of the Breast Cancer page.
Please see full Prescribing Information.

For Patients With Advanced PNET
What can patients with advanced PNET expect if prescribed AFINITOR?

  • A Phase III study of AFINITOR in patients with advanced PNET has shown that AFINITOR more than doubled median progression-free survival versus placebo2 
  • Patients taking AFINITOR for advanced PNET should be monitored for any adverse reactions2 
  • AFINITOR is taken orally, once a day2

Find out more about AFINITOR in patients with advanced PNET

Important Safety Information
Adverse Reactions: The most common adverse reactions (incidence ≥30%) were stomatitis (70%), rash (59%), diarrhea (50%), fatigue (45%), edema (39%), abdominal pain (36%), nausea (32%), fever (31%), headache (30%), and decreased appetite (30%). The most common grade 3/4 adverse reactions (incidence ≥5%) were stomatitis (7%) and diarrhea (5.5%). Deaths primarily due to adverse events during the double-blind treatment phase occurred in 7 patients taking AFINITOR.
Please see additional Important Safety Information at the bottom of the Advanced PNET page.
Please see full Prescribing Information.

References: 1. Dictionary of Cancer Terms: National Cancer Institute at NIH. http://www.Cancer.gov/dictionary. Accessed 9/23/2011. 2. AFINITOR [prescribing information]. East Hanover, NJ; Novartis Pharmaceuticals Corp; 2016. 3. Motzer RJ, Escudier B, Oudard S, et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma. Cancer. 2010;116:4256-4265.

Important Safety Information

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

Noninfectious Pneumonitis:

  • Noninfectious pneumonitis was reported in up to 19% of patients treated with AFINITOR; some cases reported with pulmonary hypertension (including pulmonary arterial hypertension) as a secondary event. The incidence of Common Terminology Criteria (CTC) grade 3 and 4 noninfectious pneumonitis was up to 4.0% and up to 0.2%, respectively. Fatal outcomes have been observed
  • Monitor for clinical symptoms or radiological changes
  • Opportunistic infections such as Pneumocystis jiroveci pneumonia (PJP) should be considered in the differential diagnosis
  • Manage noninfectious pneumonitis by dose interruption until symptoms resolve, follow with a dose reduction, and consider the use of corticosteroids
  • Discontinue AFINITOR if toxicity recurs at grade 3 or for grade 4 cases
  • For patients who require use of corticosteroids, prophylaxis for PJP may be considered
  • The development of pneumonitis has been reported even at a reduced dose

Infections:

  • AFINITOR has immunosuppressive properties and may predispose patients to bacterial, fungal, viral, or protozoal infections (including those with opportunistic pathogens)
  • Localized and systemic infections, including pneumonia, mycobacterial infections, other bacterial infections; invasive fungal infections such as aspergillosis, candidiasis, or PJP; and viral infections, including reactivation of hepatitis B virus, have occurred
  • Some of these infections have been severe (eg, leading to sepsis, respiratory failure, or hepatic failure) or fatal
  • Physicians and patients should be aware of the increased risk of infection with AFINITOR
  • Treatment of preexisting invasive fungal infections should be completed prior to starting treatment with AFINITOR
  • 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 antifungal treatment
  • PJP has been reported in patients who received everolimus, sometimes with a fatal outcome. This may be associated with concomitant use of corticosteroids or other immunosuppressive agents; consider prophylaxis for PJP when concomitant use of these agents is required

Angioedema With Concomitant Use of Angiotensin-Converting Enzyme (ACE) Inhibitors:

  • Patients taking concomitant ACE inhibitor therapy may be at increased risk for angioedema (eg, swelling of the airways or tongue, with or without respiratory impairment)
  • In a pooled analysis, the incidence of angioedema in patients taking everolimus with an ACE inhibitor was 6.8% compared to 1.3% in the control arm with an ACE inhibitor

Oral Ulceration:

  • Mouth ulcers, stomatitis, and oral mucositis have occurred in patients treated with AFINITOR at an incidence ranging from 44% to 78% across the clinical trial experience. Grade 3/4 stomatitis was reported in 4% to 9% of patients
  • In such cases, topical treatments are recommended, but alcohol-, hydrogen peroxide-, iodine-, or thyme-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

Impaired Wound Healing:

  • Everolimus delays wound healing and increases the occurrence of wound-related complications like wound dehiscence, wound infection, incisional hernia, lymphocele, and seroma
  • These wound-related complications may require surgical intervention. Exercise caution with the use of AFINITOR in the perisurgical period

Laboratory Tests and Monitoring:

  • Elevations of serum creatinine and proteinuria have been reported. Renal function (including measurement of blood urea nitrogen, urinary protein, or serum creatinine) should be evaluated prior to treatment and periodically thereafter, particularly in patients who have additional risk factors that may further impair renal function
  • Hyperglycemia, hyperlipidemia, and hypertriglyceridemia have been reported. Blood glucose and lipids should be evaluated prior to treatment and periodically thereafter. More frequent monitoring is recommended when AFINITOR is coadministered with other drugs that may induce hyperglycemia. Management with appropriate medical therapy is recommended. When possible, optimal glucose and lipid control should be achieved before starting a patient on AFINITOR
  • Reductions in hemoglobin, lymphocytes, neutrophils, and platelets have been reported. Monitoring of complete blood count is recommended prior to treatment and periodically thereafter

Drug-Drug Interactions:

  • Avoid coadministration with strong CYP3A4/PgP inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole)
  • Use caution and reduce the AFINITOR dose to 2.5 mg daily if coadministration with a moderate CYP3A4/PgP inhibitor is required (eg, amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem)
  • Avoid coadministration with strong CYP3A4/PgP inducers (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital); however, if coadministration is required, consider doubling the daily dose of AFINITOR using increments of 5 mg or less

Hepatic Impairment:

  • Exposure to everolimus was increased in patients with hepatic impairment
  • For patients with severe hepatic impairment (Child-Pugh class C), AFINITOR may be used at a reduced dose if the desired benefit outweighs the risk. For patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment, a dose reduction is recommended

Vaccinations:

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

Embryo-Fetal Toxicity:

  • Fetal harm can occur if AFINITOR is administered to a pregnant woman
  • Advise female patients of reproductive potential to use effective contraception while using AFINITOR and for 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%)

Laboratory Abnormalities:

  • The most common laboratory abnormalities (incidence ≥50%, all grades) were: decreased hemoglobin (92%) and lymphocytes (51%); and 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.

 

Abbreviations: aRCC, advanced renal cell carcinoma; mTOR, mammalian target of rapamycin; RCC, renal cell carcinoma; VEGFR-TKI, vascular endothelial growth factor receptor tyrosine inhibitor.

References: 1. Abou Youssif T, Fahmy MA, Koumakpayi IH, et al. The mammalian target of rapamycin pathway is widely activated without PTEN deletion in renal cell carcinoma metastases. Cancer. 2011;117(2):290-300. 2. AFINITOR [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2016.