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In the treatment of aRCC,

Take AIM through a targeted treatment strategy

AFINITOR (everolimus) – AiM, a targeted treatment strategy. Advise. Identify. Manage

A program designed to optimize treatment experience by establishing the benefits of AFINITOR with an emphasis on early identification, monitoring, and effective management of key adverse events (AEs)

Plan for optimal outcomes—partner with your patients to identify AEs early

The majority of adverse reactions in RECORD-1 were grade 1 or grade 21,2

  • The most common adverse reactions (incidence ≥30%) were stomatitis (44%), infections (37%), asthenia (33%), fatigue (31%), diarrhea (30%), and cough (30%)1
  • The most common grade 3 and 4 AEs with AFINITOR were infections (10%) and dyspnea (7%)1
  • Deaths primarily due to AEs during the double-blind treatment phase occurred in 5 patients taking AFINITOR2

For more information about how to identify and manage specific AEs, please use the tool below.

ADVISE

Optimize the benefit of AFINITOR through patient education

  • Patients in RECORD-1 experienced more than double the median PFS vs placebo3
    • 4.9 vs 1.9 months; HR=0.33 (95% CI: 0.25-0.43); P<0.0001 
  • Both independent (4.9 months vs 1.9 months) and investigator (5.5 months vs 1.9 months) reviews confirmed the efficacy of AFINITOR vs placebo in RECORD-12,3*
  • AFINITOR has demonstrated increased PFS in a diverse patient population1
    • RECORD-1 included patients across a range of KPS, MSKCC risk, 1 or 2 previous VEGFR-TKI therapies, previous systemic therapy, number of disease sites, and different sites of metastasis1
  • AFINITOR offers once-daily oral administration3
    • Median dose intensity of AFINITOR in RECORD-1 was 10 mg/day1
  • Early identification, careful monitoring, and timely management of AEs in the oncology setting are important to help patients maximize their time on treatment4
  • Encourage patients to proactively communicate at the earliest sign of a side effect

STOMATITIS

IDENTIFY

mTOR inhibitor-associated stomatitis (mIAS) is distinct from conventional chemotherapy-induced mucositis5

  • Stomatitis typically mimics aphthous stomatitis in clinical presentation5-7
  • Unlike mIAS, chemotherapy-induced mucositis is characterized by irregularly shaped lesions that typically lack peripheral erythema and is associated with other gastrointestinal signs or symptoms, such as7:
    • Diarrhea
    • Nausea
    • Vomiting
    • Gastroenteritis
    • Gastrointestinal hemorrhage

CLINICAL PRESENTATION OF STOMATITIS6

 

GRADE 1

Presentation: clinical exam

Erythema of the mucosa

Presentation: functional/ symptomatic

Minimal symptoms, normal diet

 
 

GRADE 2

Presentation: clinical exam

Patchy ulcerations or pseudomembranes

Presentation: functional/ symptomatic

Symptomatic but can eat and swallow, modified diet

 
 

GRADE 3

Presentation: clinical exam

Confluent ulcerations or pseudomembranes, bleeding with minor trauma

Presentation: functional/ symptomatic

Symptomatic and unable to adequately aliment or hydrate orally

 
 

GRADE 4

Presentation: clinical exam

Tissue necrosis, significant spontaneous bleeding, life-threatening consequences

Presentation: functional/ symptomatic

Symptoms associated with life-threatening consequences

 
 

GRADE 1

GRADE 2

GRADE 3

GRADE 4

Presentation: clinical exam

Erythema of the mucosa

Patchy ulcerations or pseudomembranes

Confluent ulcerations or pseudomembranes, bleeding with minor trauma

Tissue necrosis, significant spontaneous bleeding, life-threatening consequences

Presentation: functional/ symptomatic

Minimal symptoms, normal diet

Symptomatic but can eat and swallow, modified diet

Symptomatic and unable to adequately aliment or hydrate orally

Symptoms associated with life-threatening consequences

 

TYPICAL PRESENTATION OF VARYING GRADES OF STOMATITIS OBSERVED DURING CLINICAL EXAMINATION

 

GRADE 1

Identification

 
Reprinted with permission from ELSEVIER, A261.6
 

GRADE 2

Identification

 
Reprinted with permission from ELSEVIER, A261.7
 

GRADE 3

Identification

 
Reprinted with permission from ELSEVIER, 105.6
 

GRADE 4

Identification

 
Reprinted with permission from ELSEVIER, 105.6
 

GRADE 1

GRADE 2

GRADE 3

GRADE 4

Identification

 
Reprinted with permission from ELSEVIER, A261.6
Reprinted with permission from ELSEVIER, A261.7
Reprinted with permission from ELSEVIER, 105.6
Reprinted with permission from ELSEVIER, 105.6

Advise patients to:

  • Promptly report mouth ulcers, pain, discomfort, or open sores1
  • Avoid products containing alcohol, hydrogen peroxide, iodine, or thyme derivatives3

If dose reduction is required, the recommended dose is 5 mg daily and must not be lower than 5 mg daily.3 

MANAGE

Manage therapy with established strategies2,4

Use the guidelines below when considering modification of the AFINITOR 10-mg dose to manage potential AEs2,3

GRADE 1

FIRST OCCURRENCE

No dose adjustment

UPON RECURRENCE

GRADE 2

FIRST OCCURRENCE

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 10 mg

UPON RECURRENCE

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

GRADE 3

FIRST OCCURRENCE

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

UPON RECURRENCE

Per physician discretion (If event recurs at grade 3, consider discontinuation)

GRADE 4

FIRST OCCURRENCE

DISCONTINUE

UPON RECURRENCE

ADVERSE EVENT

FIRST OCCURRENCE

UPON RECURRENCE

GRADE 1

No dose adjustment

GRADE 2

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 10 mg

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

GRADE 3

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

Per physician discretion (If event recurs at grade 3, consider discontinuation)

GRADE 4

DISCONTINUE

If dose reduction is required, the recommended dose is 5 mg daily and must not be lower than 5 mg daily.3

Tips to optimize AFINITOR treatment

  • Topical treatments are recommmended.
  • Antifungal agents should not be used unless fungal infection has been diagnosed.

NONINFECTIOUS PNEUMONITIS

IDENTIFY

  • Noninfectious pneumonitis should be investigated in patients with nonspecific respiratory signs6
    • Pulmonary function tests, radiographic imaging, bronchoscopy, and bronchoalveolar lavage can be used to evaluate patients7

CLINICAL PRESENTATION OF NONINFECTIOUS PNEUMONITIS6

 

GRADE 1

Presentation

Asymptomatic, radiographic findings only

 
 

GRADE 2

Presentation

Symptomatic,* not interfering with ADL

 
 

GRADE 3

Presentation

Symptomatic,* interfering with ADL, oxygen indicated

 
 

GRADE 4

Presentation

Life-threatening, ventilator support indicated

 
 

GRADE 1

GRADE 2

GRADE 3

GRADE 4

Presentation

Asymptomatic, radiographic findings only

Symptomatic,* not interfering with ADL

Symptomatic,* interfering with ADL, oxygen indicated

Life-threatening, ventilator support indicated

MANAGE

  • Noninfectious pneumonitis should be investigated in patients with nonspecific respiratory signs6
    • Pulmonary function tests, radiographic imaging, bronchoscopy, and bronchoalveolar lavage can be used to evaluate patients7

GRADE 1

FIRST OCCURRENCE

No dose adjustment

UPON RECURRENCE

GRADE 2

FIRST OCCURRENCE

  1. Interrupt AFINITOR until resolution to grade ≤1 (discontinue if AE fails to resolve within 4 weeks)

  2. Reinitiate 5 mg

UPON RECURRENCE

Per physician discretion

GRADE 3

FIRST OCCURRENCE

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

UPON RECURRENCE

Per physician discretion (If event recurs at grade 3, consider discontinuation)

GRADE 4

FIRST OCCURRENCE

DISCONTINUE

UPON RECURRENCE

ADVERSE EVENT

FIRST OCCURRENCE

UPON RECURRENCE

GRADE 1

No dose adjustment

GRADE 2

  1. Interrupt AFINITOR until resolution to grade ≤1 (discontinue if AE fails to resolve within 4 weeks)

  2. Reinitiate 5 mg

Per physician discretion

GRADE 3

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

Per physician discretion (If event recurs at grade 3, consider discontinuation)

GRADE 4

DISCONTINUE

Advise patients to:

  • Promptly report any new or worsening symptoms, such as:
    • Fever, coughing, difficulty breathing, wheezing1

*Symptoms include cough, chest pain, sudden onset of shortness of breath, and coughing up blood.

NONHEMATOLOGIC TOXICITIES

IDENTIFY

  • Nonhematologic toxicities may present as rash and pain on palms of hands or soles of feet (hand-foot syndrome), skin exfoliation, erythema, pimples, acne, or skin lesions3

CLINICAL PRESENTATION OF NONHEMATOLOGIC TOXICITIES6

 

GRADE 1

Presentation

Papules and/or postules covering <10% BSA, which may or may not be associated with symptoms of pruritus or tenderness6

 
 

GRADE 2

Presentation

Papules and/or postules covering 10%-30% BSA, which may or may not be associated with symptoms of pruritus or tenderness; associated with psychological impact; limiting instrumental ADL6

 
 

GRADE 3

Presentation

Papules and/or postules covering >30% BSA, which may or may not be associated with symptoms of pruritus or tenderness; limiting self-care ADL; associated with local superinfection with oral antibiotics indicated6

 
 

GRADE 4

Presentation

Papules and/or postules covering any % BSA, which may or may not be associated with symptoms of pruritus or tenderness and are associated with extensive superinfection with IV antibiotics indicated; life-threatening consequences6

 
 

GRADE 1

GRADE 2

GRADE 3

GRADE 4

Presentation

Papules and/or postules covering <10% BSA, which may or may not be associated with symptoms of pruritus or tenderness6

Papules and/or postules covering 10%-30% BSA, which may or may not be associated with symptoms of pruritus or tenderness; associated with psychological impact; limiting instrumental ADL6

Papules and/or postules covering >30% BSA, which may or may not be associated with symptoms of pruritus or tenderness; limiting self-care ADL; associated with local superinfection with oral antibiotics indicated6

Papules and/or postules covering any % BSA, which may or may not be associated with symptoms of pruritus or tenderness and are associated with extensive superinfection with IV antibiotics indicated; life-threatening consequences6

MANAGE

  • Nonhematologic toxicities may present as rash and pain on palms of hands or soles of feet (hand-foot syndrome), skin exfoliation, erythema, pimples, acne, or skin lesions1

Grade 1

Adverse event

Neutropenia

First occurrence

No dose adjustment

Upon recurrence

Adverse event

Thrombocytopenia

First occurrence

No dose adjustment

Upon recurrence

Grade 2

Adverse event

Neutropenia

First occurrence

No dose adjustment

Upon recurrence

Adverse event

Thrombocytopenia

First occurrence

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 10 mg

Upon recurrence

Per physician discretion

Grade 3

Adverse event

Neutropenia

First occurrence

  1. Interrupt AFINITOR until resolution to grade ≤2 (≥1 × 109/L)

  2. Reinitiate 10 mg

Upon recurrence

Per physician discretion

Adverse event

Thrombocytopenia

First occurrence

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

Upon recurrence

Per physician discretion

GRADE 4

Adverse event

Neutropenia 

First occurrence

  1. Interrupt AFINITOR until resolution to grade ≤2 (≥1 × 109/L)

  2. Reinitiate 5 mg

Upon recurrence

Per physician discretion

Adverse event

Thrombocytopenia

First occurrence

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

Upon recurrence

Per physician discretion

Adverse event

First occurrence

Upon recurrence

Grade 1

Neutropenia

No dose adjustment

Thrombocytopenia

No dose adjustment

Grade 2

Neutropenia

No dose adjustment

Thrombocytopenia

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 10 mg

Per physician discretion

Grade 3

Neutropenia

  1. Interrupt AFINITOR until resolution to grade ≤2 (≥1 × 109/L)

  2. Reinitiate 10 mg

Per physician discretion

Thrombocytopenia

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

Per physician discretion

GRADE 4

Neutropenia 

  1. Interrupt AFINITOR until resolution to grade ≤2 (≥1 × 109/L)

  2. Reinitiate 5 mg

Per physician discretion

Thrombocytopenia

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

Per physician discretion

METABOLIC EVENTS

IDENTIFY

  • Monitor fasting blood glucose and lipid levels at the start of therapy and periodically thereafter1

MANAGE

  • Monitor fasting blood glucose and lipid levels at the start of therapy and periodically thereafter1

GRADE 1

FIRST OCCURRENCE

No dose adjustment

UPON RECURRENCE

GRADE 2

FIRST OCCURRENCE

No dose adjustment

UPON RECURRENCE

Per physician discretion

GRADE 3

FIRST OCCURRENCE

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

UPON RECURRENCE

Per physician discretion (If event recurs at grade 3, consider discontinuation)

GRADE 4

FIRST OCCURRENCE

DISCONTINUE

UPON RECURRENCE

ADVERSE EVENT

FIRST OCCURRENCE

UPON RECURRENCE

GRADE 1

No dose adjustment

GRADE 2

No dose adjustment

Per physician discretion

GRADE 3

  1. Interrupt AFINITOR until resolution to grade ≤1

  2. Reinitiate 5 mg

Per physician discretion (If event recurs at grade 3, consider discontinuation)

GRADE 4

DISCONTINUE

 
Abbreviations:
ADL, activities of daily living; aRCC, advanced renal cell carcinoma; BSA, body surface area; HCE, hypercholesterolemia; HG, hyperglycemia; HT, hypertriglyceridemia; O2, oxygen; MSKCC, Memorial Sloane Kettering Cancer Center; mTOR, mammalian target of rapamycin; PFS, progression free survival; ULN, upper limit of normal.
References:
  1. 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(18):4256-4265.
  2. Data on file. Novartis Pharma AG.
  3. AFINITOR [summary of product characteristics]. Novartis Pharma AG; May 2016.
  4. Rugo HS, Gnant M, Geberth M, et al. Everolimus-related adverse events: safety insights from BOLERO-2. Poster presented at: St. Gallen International Breast Cancer Conference; March 2013; St. Gallen, Switzerland.
  5. Sonis S, Treister N, Chawla S, Demetri G, Haluska F. Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients. Cancer. 2010;116(1):210-215.
  6. de Oliveira MA, Martins E Martins F, Wang Q, et al. Clinical presentation and management of mTOR inhibitor-associated stomatitis. Oral Oncol. 2011;47(10):998-1003.
  7. Ferté C, Paci A, Zizi M, et al. Natural history, management and pharmacokinetics of everolimus-induced-oral ulcers: insights into compliance issues. Eur J Cancer. 2011;47(15):2249-2255.
  8. Pilotte AP, Hohos MB, Polson KMO, Huftalen TM, Treister N. Managing stomatitis in patients treated with mammalian target of rapamycin inhibitors. Clin J Oncol Nurs. 2011;15(5):E83-E89.
  9. National Cancer Institute. Common terminology criteria for adverse events v3.0 (CTCAE). http://ctep.cancer.gov/protocol Development/electronic_applications/docs/ctcaev3.pdf. Published August 9, 2006. Accessed May 2, 2013.
  10. National Cancer Institute. Common terminology criteria for adverse events v3.0 (CTCAE). http://ctep.cancer.gov/protocol Development/electronic_applications/docs/ctcaev3.pdf. Published August 9, 2006. Accessed May 2, 2013.