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BOLERO-2

AFINITOR has a well-established safety profile

In the BOLERO-2 study

  • The majority of AEs were mild to moderate in severity (grade 1/2), generally manageable, and typically resolved over time1,2
  • The most common grade 3/4 AEs (incidence ≥5%) were stomatitis (8%), anemia (<8%), GGT increase (7%), dyspnea (<6%), and hyperglycemia (<6%)1
  • Serious AEs have been observed during AFINITOR therapy, including noninfectious pneumonitis, infections, and acute renal failure; on rare occasions, fatal outcomes were observed3

Partner with your patients to help identify adverse events early

Most Common AEs Reported in ≥15% of Patients With HR+/HER2- Advanced Breast Cancer1* 
AE  AFINITOR plus exemestane  Placebo plus exemestane
Stomatitis 59% 12%
Rash 39% 7%
Fatigue 37% 27%
Diarrhea 34% 19%
Nausea 31% 29%
Decreased appetite 31% 13%
Weight decreased 28% 7%
Cough 26% 12%
Dysgeusia 22% 6%
Dyspnea 22% 11%
Headache 23% 15%
Arthralgia 21% 17%
Peripheral edema 21% 6%
Anemia 21% 5%
Epistaxis 17% 1%
Vomiting 17% 13%
Pyrexia 16% 7%
Pneumonitis 16% 0%
Constipation 15% 13%
Back Pain 15% 11%
*AFINITOR is also indicated for the treatment of unresectable or metastatic, well- or moderately differentiated neuroendocrine
tumors of 
pancreatic origin in adults with progressive disease, treatment of unresectable or metastatic, well-differentiated (Grade 1 or Grade 2) non-functional neuroendocrine tumours of gastrointestinal or lung origin in adults with progressive disease and advanced renal cell carcinoma that has progressed on or after treatment with VEGF-targeted therapy.
Exemestane (25 mg daily).
Abbreviations:
AFI, AFINITOR; ABC, advanced breast cancer; AE, adverse event; BOLERO-2, Breast Cancer Trials of Oral Everolimus-2; HR+, hormone receptor-positive; PBO, placebo; VEGF, vascular endothelial growth factor.

Safety Information

AFINITOR®

Important note: Before prescribing, consult full prescribing information. 

Presentation: Tablets containing 2.5 mg, 5 mg or 10 mg of everolimus. 

Indications: Afinitor is indicated for the treatment of hormone receptor-positive, HER2/neu negative advanced breast cancer, in combination with exemestane, in postmenopausal women without symptomatic visceral disease after recurrence or progression following a nonsteroidal aromatase inhibitor. ♦ Afinitor is indicated for the treatment of unresectable or metastatic, well- or moderately-differentiated neuroendocrine tumours of pancreatic origin in adults with progressive disease.  ♦ Afinitor is indicated for the treatment of advanced renal cell carcinoma, whose disease has progressed on or after treatment with VEGF-targeted therapy. ♦ Afinitor is indicated for the treatment of unresectable or metastatic, well-differentiated (Grade 1 or Grade 2) non-functional neuroendocrine tumours of gastrointestinal or lung origin in adults with progressive disease.

Dosage: AFINITOR 10 mg dose once daily. ♦The daily dose should be taken orally at the same time every day, either consistently with or consistently without food. ♦ Dose modification: Dose interruption (with or without dose reduction) or discontinuation may be required due to adverse drug reactions (ADRs), use of moderate CYP3A4/PgP inhibitors or strong CYP3A4 inducers, hepatic status (Child-Pugh). ♦Children: not recommended for use in children or adolescents. ♦Patients with hepatic impairment: recommended dose is 7.5 mg daily in patients with mild hepatic impairment (Child-Pugh A); 5 mg daily in patients with moderate hepatic impairment (Child-Pugh B); not recommended in patients with severe hepatic impairment (Child-Pugh C), unless benefit outweighs the risk. In the latter case, a dose of 2.5 mg daily must not be exceeded.  Dose adjustments should be made if a patient’s hepatic (Child-Pugh) status changes during treatment..

Contraindications: Hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients. 

Warnings/Precautions: ♦Non-infectious pneumonitis: : Cases have been described in patients taking AFINITOR, some of these have been severe and on rare occasions, a fatal outcome was observed. A diagnosis of non-infectious pneumonitis should be considered in patients presenting with non-specific respiratory signs and symptoms such as hypoxia, pleural effusion, cough or dyspnoea, and in whom infectious, neoplastic, and other non-medicinal causes have been excluded. Opportunistic infections such as pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) should be ruled out in the differential diagnosis of non-infectious pneumonitis. In some cases, management of pneumonitis may require interruption or discontinuation of treatment. The use of corticosteroids may be indicated. For patients who require use of corticosteroids for treatment of non-infectious pneumonitis, prophylaxis for pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) may be considered. AFINITOR may be reinitiated at a lower dose. ♦Infections: AFINITOR is immunosuppressive. Localized and systemic bacterial, fungal, viral, or protozoal infections (e.g. pneumonia, aspergillosis, candidiasis, or pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) and hepatitis B reactivation) have been described in patients taking AFINITOR; some of these have been severe and occasionally fatal. Pre-existing infections should be resolved prior to starting treatment with AFINITOR. Be vigilant for symptoms or signs of infection during treatment with AFINITOR. In case of emergent infections, institute appropriate treatment promptly and consider interruption or discontinuation of AFINITOR. If a diagnosis of invasive systemic fungal infection is made, discontinue AFINITOR and treat with appropriate antifungal therapy. Prophylaxis for PJP/PCP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required. ♦Hypersensitivity reactions: have been observed with everolimus. ♦Angioedema: Patients taking concomitant ACE inhibitor therapy may be at increased risk for angioedema (e.g. swelling of the airways or tongue, with or without respiratory impairment). ♦Oral ulceration: Mouth ulcers, stomatitis, and oral mucositis have been seen in patients treated with AFINITOR. Management of these adverse reactions may require dose temporary interruption, dose reduction or discontinuation. Topical treatments are recommended, but alcohol-, hydrogen peroxide, iodine-, or thyme containing mouthwashes should be avoided. AFINITOR may be reinitiated at the same dose or at a lower dose.  ♦Renal failure: Cases of renal failure (including acute renal failure), some fatal, have been observed in patients treated with AFINITOR. Renal function of patients should be monitored particularly where patients have additional risk factors that may further impair their renal function.  ♦Laboratory tests and monitoring: Renal function, blood glucose, blood lipids, and complete blood counts are recommended prior to initiation of and periodically during treatment.  ♦Functional carcinoid tumours: The safety and efficacy of Afinitor in patients with functional carcinoid tumours have not been established. ♦Prognostic factors in neuroendocrine tumors of gastrointestinal or lung origin: In patients with non-functional gastrointestinal or lung neuroendocrine tumours and good prognostic baseline factors, e.g. ileum as primary tumour origin and normal chromogranin A values or without bone involvement, an individual benefit-risk assessment should be performed prior to the start of AFINITOR therapy. A limited evidence of PFS benefit was reported in the subgroup of patients with ileum as primary tumour origin. ♦Hepatic Impairment: Not recommended in patients with severe hepatic impairment (Child-Pugh C) unless the potential benefit outweighs the risk. ♦Vaccination: Avoid use of live vaccines and close contact with people who have received live vaccines. ♦Lactose:  Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. ♦Wound healing complications:  Impaired wound healing is a class effect of rapamycin derivatives, including AFINITOR.  Caution should be exercised with use of AFINITOR in peri-surgical period.  ♦Pregnancy: AFINITOR is not recommended during pregnancy and in women of childbearing potential not using contraception. Male patients taking AFINITOR should not be prohibited from attempting to father children. ♦Women of childbearing potential: Use highly effective contraception methods while receiving AFINITOR and for up to 8 weeks after ending treatment. ♦Breast-feeding: Women taking AFINITOR should not breast-feed. ♦Fertility: Male and female fertility may be compromised by treatment with AFINITOR. Menstrual irregularities, secondary amenorrhea, and associated luteinizing hormone (LH) / follicle stimulating hormone (FSH) imbalance have been observed in female patients receiving AFINITOR. 

Interactions: Avoid concurrent treatment with strong CYP3A4 inhibitors or PgP inhibitors (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, telithromycin). ♦Caution with moderate CYP3A4 inhibitors or PgP inhibitors (e.g. erythromycin, verapamil, diltiazem, fluconazole, ciclosporin, amprenavir, fosamprenavir, aprepitant, imatinib, dronedarone). Consider a dose decrease of AFINITOR when co-administered with moderate inhibitors. ♦Avoid concurrent treatment with strong CYP3A4 inducers or PgP inducers (e.g. rifampicin, rifabutin, carbamazepine, phenobarbital, phenytoin, efavirenz, nevirapine, dexamethasone, St. John’s Wort (Hypericum perforatum)). Consider a dose increase of AFINITOR when co-administered with strong inducers. ♦Avoid grapefruit juice, grapefruit, star fruit, Seville oranges and other foods affecting CYP3A4 or PgP. ♦Caution when used in combination with orally administered CYP3A4 substrates with a narrow therapeutic index.  

Adverse drug reactions: ♦Very common (≥10%): Infections, anemia, decreased appetite, hyperglycemia, hypercholesterolemia, dysgeusia, headache, pneumonitis, epistaxis, cough, stomatitis, diarrhea, nausea, rash, pruritus, fatigue, edema peripheral, asthenia, weight decreased. ♦Common (≥1 to <10%): Thrombocytopenia, neutropenia, leukopenia, lymphopenia, hypertriglyceridemia, hyperlipidemia, hypophosphatemia, diabetes mellitus, hypokalemia, dehydration, insomnia, hypertension, hemorrhage, dyspnea, vomiting, dry mouth, abdominal pain, oral pain, dyspepsia, dysphagia, dry skin, nail disorder, erythema, acne, hand-foot syndrome, arthralgia, renal failure, proteinuria, menstruation irregular, pyrexia, mucosal inflammation, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, blood creatinine increased. ♦Uncommon (>0.1% to <1%): Pancytopenia, hypersensitivity, ageusia, congestive cardiac failure, deep vein thrombosis, hemoptysis, pulmonary embolism, increased daytime urination, acute renal failure, amenorrhea, non-cardiac chest pain, impaired wound healing. ♦Rare (<0.1%): Pure red cell aplasia, acute respiratory distress syndrome, angioedema. ♦In clinical trials and post-marketing reports, everolimus has been associated with serious cases of hepatitis B reactivation, including fatal outcome. Reactivation of infections is an expected event during periods of immunosuppression.  In clinical trials and post-marketing spontaneous reports, everolimus has been associated with renal failure events (including fatal outcome), proteinuria, and cases of amenorrhea (secondary amenorrhea and other menstrual irregularities). In clinical studies and post marketing spontaneous reports, everolimus has been associated with cases of pneumocystis jirovecii (carinii) pneumonia (PJP, PCP), some with fatal outcome. In clinical trials and post-marketing spontaneous reports, angioedema has been reported with and without concomitant use of ACE inhibitors.

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References:
  1. Yardley DA, Noguchi S, Pritchard KI, et al. Everolimus plus exemestane in postmenopausal patients with HR+ breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 2013;30(10):870-884.
  2. Rugo HS, Pritchard KI, Gnant M, et al. Incidence and time course of everolimus-related adverse events in postmenopausal women with hormone receptor-positive advanced breast cancer: insights from BOLERO-2. Ann Oncol. 2014;25(4):808-815.
  3. AFINITOR [summary of product characteristics]. Novartis Pharma AG; 2016.