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Advise. Identify. Manage.

 

Take AIM through a targeted strategy to optimize therapy

Optimize patients’ treatment experience by establishing the benefits of AFINITOR® (everolimus) with an emphasis on early identification, monitoring, and effective management of key adverse events.

AFINITOR has a distinct, established safety profile1

Drug-related adverse events in the RADIANT-3 and -4 studies

(see Safety Results From RADIANT-3 and RADIANT-4 for complete safety information)

Discontinuation, dose adjustment, and interruption rates

  • In clinical trials, the majority of patients remained on AFINITOR3,4
    • In advanced, progressive, well-differentiated nonfunctional GI and lung NET, 20.3% of patients treated with AFINITOR discontinued therapy due to drug-related adverse events vs 4.1% with placebo4
    • In advanced, progressive pNET, 13% of patients treated with AFINITOR discontinued therapy due to drug-related adverse events vs 2% with placebo3
  • 27% of advanced, progressive pNET patients and 14% of advanced, progressive, well-differentiated nonfunctional GI and lung NET patients had their dose of AFINITOR adjusted because of adverse events4,5
  • 52% of advanced, progressive pNET patients and 61.4% of advanced, progressive, well-differentiated nonfunctional GI and lung NET patients had their dose of AFINITOR interrupted because of adverse events4,5

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

Abbreviations:
GI, gastrointestinal; NET, neuroendocrine tumor(s); pNET, pancreatic neuroendocrine tumor(s); RADIANT, RAD001 in Advanced Neuroendocrine Tumors.

ADVISE

Capitalize on the benefit of AFINITOR through patient education

  • In the RADIANT-4 study of patients with advanced, progressive, well-differentiated nonfunctional NET of GI or lung origin2*
    • AFINITOR prolonged median PFS by >7 months vs placebo (11.0 vs 3.9 months, respectively; (HR=0.48; 95% CI: 0.35-0.67; P<0.00001)
    • Median PFS with AFINITOR was >2.5 times longer vs placebo (P<0.00001)
    • Treatment with AFINITOR resulted in a 52% reduction in risk of progression or death 
  • In the RADIANT-3 study of patients with advanced, progressive NET of pancreatic origin1,3*
    • AFINITOR extended median PFS by >6 months (11.0 vs 4.6 months, respectively; (HR=0.35; 95% CI: 0.27-0.45; P<0.001)
    • AFINITOR more than doubled median PFS vs placebo (P<0.001)
    • Treatment with AFINITOR resulted in a 65% reduction in risk of progression or death
  • AFINITOR offers once-daily oral administration1
    • In RADIANT-3 and -4, median dose intensity of AFINITOR was 9.8 mg/day and 9.1 mg/day, respectively4,5

  • Early identification, careful monitoring, and timely management of adverse events in the oncology setting are important to help optimize patient adherence6
  • Encourage patients to proactively communicate at the earliest sign of a side effect

 

*The primary end point of RADIANT-3 was PFS according to the local investigator. Supportive PFS analyses were provided by independent review.5 PFS based on central radiology review was the primary end point for RADIANT-4.2
Abbreviations:
CI; confidence interval; GI, gastrointestinal; HR, hazard ratio; NET, neuroendocrine tumor(s); PFS, progression-free survival; RADIANT, RAD001 in Advanced Neuroendocrine Tumors.

STOMATITIS

IDENTIFY

  • mTOR inhibitor-associated stomatitis is distinct from conventional chemotherapy-induced mucositis in both its pathophysiology and clinical presentation6
  • In patients with advanced, progressive, well-differentiated nonfunctional GI or lung NET, or advanced, progressive pNET, stomatitis often developed within the first month of treatment4,5

Incidence of stomatitis in patients treated with AFINITOR

Clinical presentation and grading of stomatitis

Advise patients to:

  • Look out for mouth ulcers, pain, discomfort, or open sores
  • Avoid products containing alcohol, hydrogen peroxide, iodine, or thyme derivatives1

MANAGE

Manage therapy with established strategies

Use the guidelines below when considering modifications of the AFINITOR 10-mg dose to manage stomatitis.1

Guidelines for managing AFINITOR-related stomatitis

*If dose reduction is required, the recommended dose is 5 mg daily and must not be lower than 5 mg daily1

Tips to optimize AFINITOR treatment

  • Topical treatments are recommended, but mouthwashes containing alcohol, peroxide, iodine and thyme derivatives should be avoided as they may exacerbate the condition. Antifungal agents should not be used unless fungal infection has been diagnosed1
Benzocaine, butyl aminobenzoate, tetracaine hydrochloride, menthol, or phenol.
Abbreviations:
GI, gastrointestinal; mTOR, mammalian target of rapamycin; NET, neuroendocrine tumor(s); pNET, pancreatic neuroendocrine tumor(s).

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 evaluate6

Incidence of noninfectious pneumonitis in patients treated with AFINITOR

Grading of noninfectious pneumonitis

*Symptoms include chest pain, sudden onset of shortness of breath, and coughing up blood.1

In the RADIANT-3 trial, the CTCAE Version 3.0 was used.7

Chest imaging suggestive of noninfectious pneumonitis11

Radiograph shows slight increase in markings in addition to metastases11
Computed tomography scan shows stable metastatic nodules but increased interstitial markings with septal thickening11
Images are for illustrative purposes only.
Reprinted with permission of the American Thoracic Society. Copyright © 2014 American Thoracic Society. White DA et al. 2010. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med. 182:396-403. Official Journal of the American Thoracic Society.

Advise patients to:

  • Promptly report any new or worsening respiratory symptoms, such as:
    — Chest pain, sudden onset of shortness of breath, coughing up blood1

MANAGE

Manage therapy with established strategies

Use the guidelines below when considering modifications of the AFINITOR 10-mg dose to manage noninfectious pneumonitis.1

Guidelines for managing AFINITOR-related noninfectious pneumonitis

*If dose reduction is required, the recommended dose is 5 mg daily and must not be lower than 5 mg daily.1

Opportunistic infections such as pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) should be ruled out in the differential diagnosis of non-infectious pneumonitis.

Tips to optimize AFINITOR treatment

Grades 2/3:

  • Rule out infection and consider treatment with corticosteroids until clinical symptoms resolve1
Abbreviations:
ADL, activities of daily living; CTCAE, Common Terminology Criteria for Adverse Events; GI, gastrointestinal; NET, neuroendocrine tumor(s); pNET, pancreatic neuroendocrine tumor(s); RADIANT, RAD001 in Advanced Neuroendocrine Tumors.

INFECTIONS

IDENTIFY

Clinical presentation of infections

MANAGE

Manage therapy with established strategies

Use the guidelines below when considering modifications of the AFINITOR 10-mg dose to manage infections.1

Guidelines for managing AFINITOR-related infections

*Localised and systemic infections, including pneumonia, other bacterial infections, invasive fungal infections such as aspergillosis, candidiasis or pneumocystis jirovecii (carinii) pneumonia (PJP, PCP) and viral infections including reactivation of hepatitis B virus, have been described in patients taking AFINITOR. Some of these infections have been severe (e.g. leading to sepsis, respiratory or hepatic failure) and occasionally fatal.1
If dose reduction is required, the recommended dose is 5 mg daily and must not be lower than 5 mg daily.1

 

  • Pre-existing infections should be treated appropriately and should have resolved fully before starting treatment with AFINITOR. While taking AFINITOR, be vigilant for symptoms and signs of infection; if a diagnosis of infection is made, institute appropriate treatment promptly and consider interruption or discontinuation of AFINITOR1
  • Cases of pneumocystis jirovecii (carinii) pneumonia (PJP, PCP), some with fatal outcome, have been reported in patients who received everolimus. PJP/PCP may be associated with concomitant use of corticosteroids or other immunosuppressive agents. Prophylaxis for PJP/PCP should be considered when concomitant use of corticosteroids or other immunosuppressive agents are required1
Abbreviation:
IV, intravenous.

RASH

IDENTIFY

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

Incidence of rash in patients treated with AFINITOR

Clinical presentation of rash

MANAGE

Manage therapy with established strategies

Use the guidelines below when considering modifications of the AFINITOR 10-mg dose to manage rash.1

Guidelines for managing AFINITOR-related rash

*If dose reduction is required, the recommended dose is 5 mg daily and must not be lower than 5 mg daily.1
Abbreviations:
BSA, body surface area; GI, gastrointestinal; NET, neuroendocrine tumor(s); pNET, pancreatic neuroendocrine tumor(s).

METABOLIC EVENTS

IDENTIFY

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

Incidence of metabolic events (hyperglycemia) in patients treated with AFINITOR

MANAGE

Manage therapy with established strategies

Use the guidelines below when considering modifications of the AFINITOR 10-mg dose to manage metabolic events.1

Guidelines for managing AFINITOR-related metabolic events

*If dose reduction is required, the recommended dose is 5 mg daily and must not be lower than 5 mg daily.1
Abbreviations:
GI, gastrointestinal; NET, neuroendocrine tumor(s); pNET, pancreatic neuroendocrine tumor(s).

HEMATOLOGIC TOXICITIES

IDENTIFY

Clinical presentation of hematologic toxicities lab values based on CTCAE v3.0

Febrile neutropenia7

  • Grade 3: ANC <1.0 x 109/L with a temperature of ≥38.5°C
  • Grade 4: Life-threatening consequences (eg, septic shock, hypotension, acidosis, necrosis)

MANAGE

Manage therapy with established strategies

Use the guidelines below when considering modifications of the AFINITOR 10-mg dose to manage neutropenia and thrombocytopenia.1

Guidelines for managing AFINITOR-related hematologic toxicities

*If dose reduction is required, the recommended dose is 5 mg daily and must not be lower than 5 mg daily.1

The medical judgment of the treating physicians should guide all treatment decisions.
Abbreviations:
ANC, absolute neutrophil count; CTCAE, Common Terminology Criteria for Adverse Events; LLN, lower limits of normal; RADIANT, RAD001 in Advanced Neuroendocrine Tumors.
References:
  1. AFINITOR [summary of product characteristics]. Basel, Switzerland: Novartis Pharma AG; May 2016.
  2. Yao JC, Fazio N, Singh S, et al. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016;387(10022):968-977.
  3. Yao JC, Shah MH, Ito T, et al; for the RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study Group. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364(6):514-523.
  4. Data on file. Novartis Pharma AG.
  5. Data on file. Novartis Pharma AG.
  6. 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 13-16, 2013; St. Gallen, Switzerland.
  7. National Cancer Institute. Common Terminology Criteria for Adverse Events v3.0 (CTCAE). http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf. Published August 9, 2006. Accessed May 2, 2013.
  8. 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.
  9. 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.
  10. Cawley MM, Benson LM. Current trends in managing oral mucositis. Clin J Oncol Nurs. 2005;9(5):584-592.
  11. White DA, Camus P, Endo M, et al. Noninfectious pneumonitis after everolimus therapy for advanced renal cell carcinoma. Am J Respir Crit Care Med. 2010;182(3):396-403.