G-Afi-1065817_g 2013 Afi Breast Adv Bc Aim Rn Brochure

8/12/2019 G-Afi-1065817_g 2013 Afi Breast Adv Bc Aim Rn Brochure

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Please see Basic Succinct Statement on pages 25-26.Please see accompanying Summary of Product Characteristics.

AFINITOR is indicated for the treatment of hormone receptor-positive, HER2/neu negativeadvanced breast cancer, in combination with exemestane, in postmenopausalwomen without symptomatic visceral disease after recurrence or progression following anonsteroidal aromatase inhibitor.

This brochure is part of a program designed to optimize treatment with

AFINITOR by providing you with essential information about treatment inhormone receptor-positive (HR+)/HER2-negative advanced breast cancer.

Advise. Identify. Manage.Take AIM through a targeted treatment strategy


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Please see Basic Succinct Statement on pages 25 -26.Please see accompanying Summary of Product Characteristics.

Starting the treatment conversation with your patients ...................................................................................1

Discussing HR+/HER2 aBC with your patients .............. ............. .............. .............. ............. .............. ............

Outlining treatment options for advanced breast cancer ............. .............. .............. ............. .............. ............. ..

Sharing why AFINITOR may be the right next step ............. .............. .............. ............. .............. ............. ........

Advise .......................................................................................................................................

Explaining the benets of AFINITOR ..............................................................................................................

Partnering with your patients to optimize AFINITORs once-daily oral administration ..................................

Identify .....................................................................................................................................9-18

Preparing your patients for optimal treatment through education on the AFINITOR safety prole ................

Key adverse events .............................................................................................................................................

Partnering with your patients to identify adverse events early ............. ............. .............. ............. .............. . 11-

Stomatitis ............ .............. ............. .............. .............. ............. .............. .............. ............. .............. .......... 11

Noninfectious pneumonitis ......................................................................................................................13-

Rash ..............................................................................................................................................................

Metabolic events .......................................................................................................................................... Hematologic toxicities .................................................................................................................................

Manage

Managing your patients therapy with established strategies ............ .............. ............. .............. .............. .. 19-2

Tips to optimize AFINITOR treatment .............................................................................................................2

Nurse checklist ...................................................................................................................................................

Table of Contents



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Please see Basic Succinct Statement on pages 25-26.Please see accompanying Summary of Product Characteristics.

Discussing HR+/HER2 aBC with your patientsYour patients may have questions about their disease, especially somescientic terms, such as hormone receptor-positive.You may want to talk to your patients about:

The difference between early and advanced breast cancer, and more specically the difference betweenearly and metastatic disease

In advanced, or metastatic, breast cancer the disease has progressed beyond the breast to other parts

of the body1,2

The multiple types of advanced breast cancer The results of the patients biopsy will determine the type of advanced breast cancer the patient has1

It is important to know the type of advanced breast cancer, because it helps the doctor know whichtreatment may be most effective1

The meaning of receptor status Hormone receptor-positive (HR+) refers to the status of a tumor whose cells have receptors for certain

hormones, most commonly estrogen1

HR+ tumors depend on the presence of estrogen or, less commonly, progesterone for tumor growth1,3

Estrogen promotes the growth of 2 out of 3 breast cancers1,3

If your patient has recently been diagnosed with advanced breast cancer, she may feel overwhelmedby a range of emotions. It is important to provide appropriate resources and to remind her that she is notalone. Partner with your patients to make sure they are empowered to take control of the next stage oftheir treatment.

Starting the treatmentconversation with your patientsThis brochure is designed to guide and facilitateconversations about AFINITOR between you andyour patients.

Included are answers to many of the most commonquestions patients have about their cancer, common treatments, and reasons why this particular treatmenthas been recommended for their disease.Also provided is a checklist, which you can use to makesure your patient is ready for treatment with AFINITOR.

2


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4


Sharing why AFINITOR may be the right next stepAFINITOR is a unique treatment option6 AFINITOR is an oral, once-daily prescription medication which, in combination with exemestane,

is approved to treat hormone receptor-positive, HER2/neu negative advanced breast cancer, inpostmenopausal women without symptomatic visceral disease after recurrence or progressionfollowing a nonsteroidal aromatase inhibitor6

AFINITOR may help extend the benets of hormonal therapy when it can no longer keep the diseaseunder control6-8

How AFINITOR worksWhen a hormonal therapy stops working and the cancer progresses, AFINITOR, combined with thehormonal therapy exemestane, offers a unique treatment option for advanced breast cancer. TakingAFINITOR with exemestane can increase the period of time before the disease progresses compared totaking exemestane alone.6

Outlining treatment options foradvanced breast cancerTreatment options for advanced breast cancer can be dividedinto 2 categories 3:

1. Local therapy for a tumor that is causing problems 3,4

Surgery to relieve pressure on tissues or stabilize a broken bone Radiation therapy

2. Systemic (whole-body) therapy for cancer cells throughout the body 3

Hormonal therapy For women with HR+/HER2-negative advanced breast cancer, hormonal therapy, such as an aromataseinhibitor (AI), is the standard of care. Over time, however, this therapy can stop working and the cancercan recur or spread to another site in the body. This is called disease progression5

Targeted therapy Targeted therapy, such as AFINITOR, attacks specic parts of cells, including cancer cells, such asproteins, that allow all cells, including cancer cells, to live and grow. Targeted therapy allows thephysician to choose therapies that are tailored to the specic type of breast cancer, and often, targetedtherapy is given at the same time as other therapies3

Chemotherapy Chemotherapy works by traveling through the bloodstream and killing any quickly growing cells3

It is used in all types of cancers but is typically reserved for patients who have multiple tumors or adangerous metastasis because it can kill healthy cells as well as cancer cells3

AFINITOR exemestaneplus

Longer disease control than exemestane aloneEducating patients on the clinical benets and potential side effects

of AFINITOR is key in empowering them for their next stage ofadvanced breast cancer treatment


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Please see Basic Succinct Statement on pages 25-26.Please see accompanying Summary of Product Characteristics. 6

Advice for your patients: Why AFINITOR? AFINITOR plus exemestane decreased the chance of tumors growing and spreading by more than halfcompared to treatment with exemestane alone 6

Explaining the benets of AFINITORBOLERO-2 Clinical Trial Results6The BOLERO-2 clinical trial was conducted to determine whether adding AFINITOR to exemestane extendedprogression-free survival (PFS) vs exemestane therapy alone.

The study conrmed that adding AFINITOR to exemestane more than doubled the length of PFS comparedto treatment with exemestane alone

Based on the investigator assessment, median PFS was 7.8 months with AFINITOR plus exemestane vs3.2 months with exemestane alone

In the central assessment, median PFS was 11 months with AFINITOR plus exemestane vs 4.1 monthswith exemestane alone

Patients treated with AFINITOR plus exemestane had a 55% lower risk of progression according toinvestigator assessment

All preplanned patient subgroups in the trial (eg, age, sensitivity to prior hormonal therapy, number of organsinvolved, status of bone-only lesions at baseline, and presence of visceral metastasis) derived signicantPFS benet

AFINITOR, in combination with exemestane, is the only therapy proven superior to an AI alone followingrecurrence or progression on a nonsteroidal AI in a phase 3 clinical trial

P


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Partnering with your patients to optimizeAFINITORs once-daily oral administration6

Advise patients about how to take AFINITOR6 The starting dose is 10 mg once daily in combination with exemestane AFINITOR is given in combination with exemestane (25 mg daily)

to treat HR+/HER2-negative advanced breast cancer Conveniently taken at home, not in a doctors ofce Patients should swallow tablets whole with a full glass of water

Patients should not chew or crush tablets AFINITOR should not be taken with foods and medications that can

interact with its metabolism (eg, grapefruit)

Advise patients about how to store AFINITOR6 Store in the original package in order to protect from light and moisture Throw away AFINITOR that is out of date or no longer needed

Do not use after the expiry date that is stated on the cartonand blister foil. The expiry date refers to the last day of that month

Do not use any pack that is damaged or shows signs of tampering Open the foil package with scissors just before taking the tablet

Advise patients that strategies exist for managingadverse events Like most oncology medications, AFINITOR may cause side effects1,6

Early identication, careful monitoring, and timely management of adverse events in the oncology settingare important to help patients optimize treatment9

Advice for your patients: How to take AFINITOR For treatment of advanced breast cancer, AFINITORmust be taken in combination with exemestane 6

Taking AFINITOR as directed gives your patients the best chance for optimizing their treatment 6

Side effects may occur, but strategies are available to help manage them 9

Advise

10 mgOnce Daily

Early and open communication is key in preparing patients for thisnext stage of their treatment journey


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Please see Basic Succinct Statement on pages 25 -26.Please see accompanying Summary of Product Characteristics. 10

*AFINITOR is currently also approved for the treatment of unresectable or metastatic, well- or moderately-differentiated neuroendocrine tumors of pancreatic originin adults with progressive disease and advanced renal cell carcinoma that has progressed on or after treatment with VEGF-targeted therapy.6

mTOR = mammalian target of rapamycin.VEGF = vascular endothelial growth factor.

Preparing your patients for optimal treatment througheducation on the AFINITOR safety proleAFINITOR has an established safety prole6,10More than 100,000 patients have been treated worldwide across approved indications since the rstoncology approval of AFINITOR in 2009.7*

The safety prole of AFINITOR is consistent with the known adverseevents of mTOR inhibitors10 mTOR inhibitors have a distinct safety prolekey adverse events include stomatitis, noninfectious

pneumonitis, hematologic and nonhematologic toxicities, and metabolic events9,11,12

In the BOLERO-2 study: The majority of adverse events were mild to moderate in severity (grade 1/2), generally manageable, and typically

resolved over time9,13

The most common grade 3/4 adverse events (incidence


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Partnering with your patients to identify adverseevents earlySigns and symptoms of stomatitis In BOLERO-2, the median time to onset was approximately 2 weeks13

The mouth ulcers associated with AFINITOR therapy, mTOR inhibitorassociated stomatitis (mIAS), aredistinct from the mouth ulcers that can occur during chemotherapy14

Similar to canker sores (aphthous ulcers), mIAS is characterized by discrete, ovoid, supercial, well-demarcated ulcerations with a grayish-white pseudomembrane14

Chemotherapy-induced mucositis is characterized by irregularly shaped lesions that typically lackperipheral erythema and is associated with other gastrointestinal signs or symptoms (eg, diarrhea,nausea, vomiting, gastroenteritis, gastrointestinal hemorrhage)characteristics not seen in theanalysis of mIAS14

Incidence of Stomatitisin BOLERO-2 (AFINITOR + exemestane arm)10

All Grades Grade 3 Grade 459% 8% 0%

Grading of stomatitis

Identify

Reprinted from de Oliveira MA, et al.16 Reprinted from Cawley MM, et al.18 Reprinted from Ferte C, et al.17 Reprinted from Cawley MM, et al.18

Common Terminology Criteria for Adverse Events (CTCAE), Version 3.015

Grade 1 Grade 2 Grade 3 Grade 4

P r e s e n t a t i o n

C l i n

i c a l E x a m Erythema of the mucosa Patchy ulcerations or

pseudomembranes

Conuent ulcerations

or pseudomembranes,bleeding with minor trauma

Tissue necrosis, signicant

spontaneous bleeding,life-threateningconsequences

F u n c t i o n a

l /

S y m p t o m a t i c

Minimal symptoms,normal diet

Symptomatic but can eatand swallow modied diet

Symptomatic and unableto adequately aliment orhydrate orally

Symptoms associatedwith l ife-threateningconsequences

I d e n t i

c a t i o n


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Partnering with your patients to identify adverseevents early (cont)Signs and symptoms of noninfectious pneumonitis In BOLERO-2, the median time to onset was approximately 16 weeks13

Noninfectious pneumonitis is characterized by nonmalignant inltration of the lungs19

Patients may be asymptomatic or have nonspecic respiratory signs and symptoms19

Symptomatic cases are usually mild to moderate and reversible; however, a small proportion may besevere and on rare occasions fatal outcomes have been reported6,7,19

Noninfectious pneumonitis should be investigated in patients with nonspecic respiratory signs(pulmonary function tests, radiographic imaging, bronchoscopy, and bronchoalveolar lavage can be usedto evaluate)7,9

Identify

Grading of noninfectious pneumonitis

CTCAE, Version 3.015

Grade 1 Grade 2 Grade 3 Grade 4

Asymptomatic,radiographicndings only

Symptomatic, not interferingwith activities of daily living(ADL)

Symptomatic, interferingwith ADL; oxygen indicated

Life-threatening;ventilatory supportindicated

Images courtesy of Robert Motzer, MD.20

Radiological scans of chest suggestive of noninfectious pneumonitis 20

Airspace Consolidation Ground GlassOpacity (GGO)Patchy Distributionof GGO

Extensive GGOConsolidation

Incidence of Noninfectious Pneumonitisin BOLERO-2 (AFINITOR + exemestane arm)10

All Grades Grade 3 Grade 416% 3% 0%

P r e s e n t a t i o n


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Incidence of Metabolic Eventsin BOLERO-2 (AFINITOR + exemestane arm)7

All Grades Grade 3 Grade 4

Hyperglycemia 67% 7% 7.75-10.34mmol/L

>2.5-5.0x ULN

FGV>13.9-27.8mmol/L

>10.34-12.92mmol/L

>5.0-10x ULN

FGV>27.8mmol/L

>12.92mmol/L

>10x ULN


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Advice for your patients: Identifying adverse events AFINITOR may cause side effects, and every patients experience may be different 1

Reporting symptoms or side effects to the healthcare team may not always result in treatmentdiscontinuation or interruption. Encourage patients to promptly share any changes in how they feel

Monitor complete blood count at the start of therapy and periodically thereafter6

Incidence of Hematologic Toxicities in BOLERO-2 (AFINITOR + exemestane arm)7

All Grades Grade 3 Grade 4

Thrombocytopenia (platelet count decreased) 54% 3%


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Management of adverse reactions may require dose reduction and/or temporary interruption of AFINITOR therapy6

In the BOLERO-2 clinical trial the majority of patients did not require adose reduction 9

Managing your patients therapy withestablished strategies 7,9

Communicate to patients that: The healthcare team has many ways to help manage side effects to help patients stay on treatment for

as long as possible6

Management strategies may include temporary dose adjustments or prescription medications7

The healthcare team may also recommend a nonprescription medicine to ease certain symptoms7

Manage

If dose reduction is required, the recommended dose is 5 mg daily and must not be lower than 5 mg daily.6 The medical judgment of the treating physicians should guide all treatment decisions.

* If toxicity is tolerable, no dose adjustment required.

Until recovery to grade

1. Until recovery to grade 1. Discontinue if failure to recover within 4 weeks.Until recovery to grade 2 ( 1x109 /L).||Noninfectious pneumonitis and nonhematologic toxicities: if event recurs at grade 3, consider discontinuation.

GRADE 1

GRADE 2

FIRST OCCURRENCE

No Dose Adjustment

All Other Adverse Events

Thrombocytopenia and Neutropenia

All Other Adverse Events||

Neutropenia

ADVERSE EVENT

GRADE 4

GRADE 3

Per Physician Discretion



Metabolic Events(eg, hyperglycemia, dyslipidemia)Neutropenia

Per Physician DiscretionNo Dose Adjustment

Reinitiate

Reinitiate

Reinitiate

Thrombocytopenia Per Physician DiscretionInterruptAFINITOR1

Reinitiate10mg

2

InterruptAFINITOR

InterruptAFINITOR

110mg

2

215mg

InterruptAFINITOR

15mg

2

StomatitisNonhematologic Toxicities*

InterruptAFINITOR

InterruptAFINITOR

110mg

Reinitiate Reinitiate 2 45mg

3

NoninfectiousPneumonitis Per Physician Discretion

InterruptAFINITOR

1Reinitiate

5mg2

Discontinue

UPON RECURRENCE

Of the dose-modification events thatresolved with re-initiation of the full 10-mgdose, 76% resolved within 2 weeks 9

61%required 1 dose

reduction 9

39%did not requirea dosereduction 9


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Tips to optimize AFINITOR treatmentStomatitis Tips:Grade 1:

Recommend management with nonalcoholic or saltwater (0.9%) mouthwash several times a day7

Grade 2/3:

Recommend management with topical analgesic mouth treatments* with or without topicalcorticosteroids7

Noninfectious Pneumonitis Tips:Grade 2/3:

Rule out infection and consider treatment with corticosteroids until symptoms improve to grade 16

*Benzocaine, butyl aminobenzoate, tetracaine hydrochloride, menthol, or phenol. Triamcinolone oral paste.

Advice for your patients: stomatitis Look out for mouth ulcers, pain, discomfort, or open sores 6

Avoid products containing alcohol, hydrogen peroxide, iodine, or thyme derivatives 6

Manage

Advice for your patients: noninfectious pneumonitis Promptly report any new or worsening respiratory symptoms, such as:

Nonspecic respiratory signs and symptoms of noninfectious pneumonitis may include hypoxia,pleural effusion, cough, or dyspnoea 6

Partnering with your patients is critical to managing side effects andoffering the best possible treatment


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NotesNurse checklistBefore patients start therapy with AFINITOR, conrm that theyare eligible 6 Include the following steps and discussions as part of your consult with the patient:

Review the full medical history with your patient, including:

Perform tests before initiation of AFINITOR treatment and periodically thereafter to assess kidney andliver function, blood glucose and lipid levels, and complete blood count

Inquire whether the patient is allergic to everolimus, Rapamune, or Torisel,or to the inactive ingredients in AFINITOR tablets, including lactose

Anticipate any potential drug-drug interactions by cataloguing all medicationsthe patient is taking

When taken together, some medicines can lower or raise the amount ofAFINITOR in the blood and can cause serious side effects

Ask patients about all their current medications and nonprescription supplements Specically ask about any medicine for infections, tuberculosis, seizures,

HIV/AIDS, cardiovascular disease, and medicines that suppress theimmune system

Consult product labeling for further information about any potential conicts Ask whether the patient is scheduled to receive any vaccinations. Patients should not receive livevaccines during treatment with AFINITOR

Kidney disease Liver disease Diabetes or high blood sugar

High blood cholesterol levels Previous hepatitis B Any current infections

Rapamune (sirolimus) and Torisel (temsirolimus) are registered trademarks of Wyeth Pharmaceuticals Inc.


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Please see accompanying Summary of Product Characteristics. 26

Basic Succinct StatementAFINITOR 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 negativeadvanced breast cancer, in combination with exemestane, in postmenopausal women without symptomaticvisceral disease after recurrence or progression following a non-steroidal aromatase inhibitor.Dosage: one 10 mg AFINITOR Tablet once daily. The daily dose should be taken orally at the same timeevery day, either consistently with or consistently without food. Dose adjustment: Dose adjustmentmay be required due to adverse drug reactions (ADRs), use of moderate CYP3A4/PgP inhibitors or strongCYP3A4 inducers, or hepatic status (Child-Pugh). Children: not recommended for use in children oradolescents. Patients with hepatic impairment: recommended dose is 7.5 mg daily in patients withmild hepatic impairment (Child-Pugh A); 5 mg daily in patients with moderate hepatic impairment (Child-Pugh B) and the dose may be decreased to 2.5 mg daily if not well tolerated; not recommended in patientswith severe hepatic impairment (Child-Pugh C), unless benet outweighs the risk. In the latter case, a doseof 2.5 mg daily must not be exceeded.Contraindications: Hypersensitivity to the active substance, to other rapamycin derivatives or to any ofthe excipients. Warnings/Precautions: Non-infectious pneumonitis: Cases have been described in patientstaking 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-specicrespiratory signs and symptoms such as hypoxia, pleural effusion, cough or dyspnea, and in whominfectious, neoplastic, and other non-medicinal causes have been excluded. In some cases, managementof pneumonitis may require interruption or discontinuation of treatment. The use of corticosteroids may beindicated. 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, and hepatitis B reactivation) have been described in patients taking AFINITOR; some ofthese have been severe and occasionally fatal. Pre-existing infections should be resolved prior to startingtreatment 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 ordiscontinuation of AFINITOR. If a diagnosis of invasive systemic fungal infection is made, discontinueAFINITOR and treat with appropriate antifungal therapy. Hypersensitivity reactions have beenobserved with everolimus. Oral ulceration: Mouth ulcers, stomatitis, and oral mucositis have been seenin patients treated with AFINITOR. Management of these adverse reactions may require dose temporaryinterruption, dose reduction or discontinuation. Topical treatments are recommended, but alcohol-, hydrogenperoxide, iodine-, or thyme containing mouthwashes should be avoided. AFINITOR may be reinitiated at thesame dose or at a lower dose.

Renal failure: Cases of renal failure (including acute renal failure), some fatal, have been observed inpatients treated with AFINITOR. Renal function of patients should be monitored particularly where patientshave 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 initiationof and periodically during treatment. Hepatic Impairment: Not recommended in patients with severehepatic impairment (Child-Pugh C) unless the potential benet outweighs the risk. Vaccination: Avoid useof live vaccines and close contact with people who have received live vaccines. Pregnancy: AFINITORshould not be given to pregnant women unless the potential benet outweighs the potential risk to the fetus.Male patients taking AFINITOR should not be prohibited from attempting to father children. Women ofchildbearing potential: Use highly effective contraception methods while receiving AFINITOR and for upto 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. Menstrualirregularities, secondary amenorrhea, and associated luteinizing hormone (LH) / follicle stimulatinghormone (FSH) imbalance have been observed in female patients receiving AFINITOR.Interactions: Avoid concurrent treatment with strong CYP3A4 inhibitors or PgP inhibitors (e.g. ketoconazolitraconazole, ritonavir, clarithromycin, telithromycin). Caution with moderate CYP3A4 inhibitors or PgPinhibitors (e.g. erythromycin, verapamil, diltiazem, uconazole, ciclosporin, amprenavir, fosamprenavir,aprepitant). 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, prednisone, prednisolone,St. Johns Wort (Hypericum perforatum )). Consider a dose increase of AFINITOR when co-administered withstrong inducers. Avoid grapefruit juice, grapefruit, star fruit, Seville oranges and other foods affectingCYP3A4 or PgP. Caution when used in combination with orally administered CYP3A4 substrates with anarrow therapeutic index.Adverse drug reactions: Very common ( 10%): Infections, anemia, thrombocytopenia, decreasedappetite, hyperglycemia, hypercholesterolemia, dysgeusia, headache, pneumonitis, epistaxis, cough,dyspnea, stomatitis, diarrhea, nausea, vomiting, rash, pruritus, fatigue, peripheral edema, asthenia,weight decreased. Common ( 1 to


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References: 1. National Comprehensive Cancer Network. NCCN Guidelines For PatientsTM. Breast Cancer. V 2.2011. http://www.nccn.org/patients/guidelines/breast/index.html. Accessed September 9, 2013. 2. Susan G. Komen For The Cure Facts For Life: MetastaticBreast Cancer. http://ww5.komen.org/uploadedfiles/Content_Binaries/806-03201a.pdf. Published 2008. Accessed September 9, 2013.3. American Cancer Society Breast Cancer. http://www.cancer.org/acs/groups/cid/documents/webcontent/003090-pdf.pdf. PublishedJune 11, 2012. Accessed September 9, 2013.4. Breast Cancer.Org. Treatments for Metastatic Cancer. http://www.breastcancer.org/symptoms/types/recur_metast/treat_metast. Published September 17, 2012. Accessed September 9, 2013.5. Schiff, R, MassarwehS, Shou J, Osborne CK. Breast cancer endocrine resistance: how growth factor signaling and estrogen receptor coregulators modulateresponse.Clin Cancer Res . 2003;9:447s-454s.6. AFINITOR [summary of product characteristics]. Novartis Pharma AG; 2013. 7. Dataon file. Novartis Pharma AG.8. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptorpositiveadvanced breast cancer.N Engl J Med . 2012;366:520-529.9. 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.10. Piccart M, Baselga J, Noguchi S, et al. Final progression-free survival analysis of BOLERO-2: a phase III trial ofeverolimus for postmenopausal women with advanced breast cancer. Poster presented at: San Antonio Breast Cancer Symposium;December, 2012; San Antonio, TX.11. Sankhala K, Mita A, Kelly K, Mahalingam D, Giles F, Mita M. The emerging safety profile ofmTOR inhibitors, a novel class of anticancer agents.Targ Oncol . 2009;4:135-142.12. Grnwald V, Weikert S, Pavel ME, et al. Practicalmanagement of everolimus-related toxicities in patients with advanced solid tumors.Onkologie . 2013;36:295-302.13. Rugo HS,Gnant M, Geberth M, et al. Everolimus-related adverse events: safety insights from BOLERO-2. Abstract presented at: St. GallenInternational Breast Cancer Conference; March 2013; St. Gallen, Switzerland.14. Sonis S, Treister N, Chawla S, Demetri G, HaluskaF. Preliminary characterization of oral lesions associated with inhibitors of mammalian target of rapamycin in cancer patients.Cancer .2010;116:210-215.15. National Cancer Institute. Common terminology criteria for adverse events (CTCAE) v3.0. http://ctep.cancer.gov/protocolDevelopment/electronic_applications /docs/ctcaev3.pdf. Published May 09, 2006. Accessed June 12, 2013.16. de OliveiraMA, Martins e Martins F, Wang Q, et al. Clinical presentation and management of mTOR inhibitor-associated stomatitis.Oral Oncol .2011;47:998-1003.17.Ferte C, Paci A, Zizi M, et al. Natural history, management and pharmacokinetics of everolimus-induced-oralulcers: insights into compliance issues.Eur J Cancer . 2011;47:2249-2255.18. Cawley MM, Benson LM. Current trends in managingoral mucositis.Clin J Oncol Nursing . 2005;9:584-592.19. Moldawer N, Wood L. Management of key adverse events associatedwith everolimus therapy.Kidney Cancer J . 2010;8:51-59.20. White A, Schwartz L, Dimitrijevic S, Scala LD, Hayes W, Gross SH.Characterization of pneumonitis in patients with advanced non-small cell lung cancer treated with everolimus (RAD001). J Thorac Oncol .2009;4:1357-1363.

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G-Afi-1065817_g 2013 Afi Breast Adv Bc Aim Rn Brochure