Download Fact Sheet on Afinitor® in Advanced Renal Cell Carcinoma (RCC)

FOR MEDIA USE ONLY
Fact Sheet on Afinitor® in Advanced Renal Cell Carcinoma (RCC)
Afinitor is an oral drug approved for the treatment of advanced renal cell carcinoma in the European Union (EU)
1
following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy) . Afinitor inhibits the
mTOR (mammalian target of rapamycin) pathway, which is responsible for multiple cellular functions including growth,
1
metabolism and angiogenesis .

About RCC


The
Advanced
RCC
Treatment
Journey
Renal cell carcinoma (RCC) is the most common type of kidey cancer, accounting for 80% to
85% of malignant kidney tumors. RCC develops in the lining of the kidney’s tubes and grows
2,3
into a mass, or tumor
4,5
RCC accounts for approximately 4% of all new cancer cases worldwide . Annually, there are
6
an estimated 330,000 new RCC cases and more than 100,000 deaths
More than one-third of patients with RCC have metastatic, or advanced, cancer at the time of
7
diagnosis, meaning the cancer cells have spread to other parts of the body
A patient’s treatment journey will vary depending on the stage of the disease at diagnosis.
8
Treatments for advanced RCC may include one or more of the following :
9
 Surgery: Removing all or part of the kidney (partial or full nephrectomy)
 First-line therapy: There are several therapies or combinations that may be considered
9
after surgery to control or slow the growth of the tumor
 Second-line therapy: Treatment that is given when initial therapy does not work or stops
9
working
 Third-line therapy: Treatment that is given when both first- and second-line therapies have
9
failed to work or stops working
Different medicines are appropriate for different patients, work in different ways, and have different
side effects. There are many therapies available to treat advanced RCC and it is possible a
patient may need multiple lines of therapy. Not every treatment option is available or approved for
use in every stage.
Afinitor in
Advanced
RCC
Mechanism
of Action
Afinitor is approved for the treatment of patients with advanced renal cell carcinoma, whose
disease has progressed on or after treatment with vascular endothelial growth factor (VEGF)1
targeted therapy .
Afinitor is an oral mTOR inhibitor approved for the treatment of advanced RCC.
Afinitor inhibits mTOR, a protein located inside cells responsible for regulating important signaling
pathways. When overactivated, this can lead to uncontrolled cell growth, increased cellular
10
metabolism and the creation of new blood vessels .
Tumor Cell
In in vivo/in vitro studies, inhibition of the mTOR
pathway by Afinitor has been shown to:
• Reduce tumor cell growth and
11
proliferation
11,12
• Reduce cell metabolism
13,14
• Decrease tumor angiogenesis
Novartis Pharma AG
CH-4002 Basel Switzerland
©Novartis 2015
May 2015
G-AFI-1113233
FOR MEDIA USE ONLY
Efficacy
In patients with advanced RCC whose disease has progressed on or after treatment with VEGFtargeted therapy:
 Afinitor more than doubled median time without tumor growth and reduced the risk of disease
progression or death (progression-free survival) by 67% compared with placebo in the pivotal
16
Phase III RECORD-1 trial, which formed the basis of global approvals for Afinitor

Safety

The most common adverse reactions (incidence ≥ 15%) from the RECORD-1 pivotal trial
were stomatitis (44%), infections (37%), asthenia (33%), fatigue (31%), cough (30%), diarrhea
(30%), rash (29%), nausea (26%), anorexia (25%), peripheral edema (25%), dyspnea (24%),
vomiting (20%), pyrexia (20%), mucosal inflammation (19%), headache (19%) and epistaxis
16
(18%)
The most common grade 3-4 adverse reactions (incidence ≥ 3%) were infections, dyspnea,
fatigue, stomatitis, dehydration, pneumonitis, abdominal pain, and asthenia16
*Treatment approvals vary by country. Please check approved treatments in your country.
About Afinitor (everolimus)
®
Afinitor (everolimus) is approved in more than 115 countries including the United States and European Union for
advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted
therapy. It is also approved in more than 95 countries, including the United States and throughout the European
Union, for locally advanced, metastatic or unresectable progressive neuroendocrine tumors of pancreatic origin.
Afinitor (everolimus) is approved in the European Union for the treatment of hormone receptor-positive, human
epidermal growth factor receptor-2 negative (HR+/HER2-) advanced breast cancer, in combination with exemestane,
in postmenopausal women without symptomatic visceral disease after recurrence or progression following a nonsteroidal aromatase inhibitor (NSAI). In the United States, Afinitor is approved for the treatment of postmenopausal
women with advanced hormone receptor-positive, HER2 negative (advanced HR+/HER2-) breast cancer in
combination with exemestane after failure of treatment with letrozole or anastrozole.
Everolimus is also available from Novartis for use in certain non-oncology patient populations under the brand names
®
®
®
®
Afinitor or Votubia , Certican and Zortress and is exclusively licensed to Abbott and sublicensed to Boston
Scientific for use in drug-eluting stents.
Indications vary by country and not all indications are available in every country. The safety and efficacy profile of
everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials,
there is no guarantee that everolimus will become commercially available for additional indications anywhere else in
the world.
Important Safety Information about everolimus tablets
Afinitor/Votubia can cause serious side effects including lung or breathing problems, infections (including sepsis), and
kidney failure, which can lead to death. Patients taking concomitant angiotensin-converting enzyme (ACE) inhibitors
may be at an increased risk for angioedema. Mouth ulcers and mouth sores are common side effects. Afinitor/Votubia
can affect blood cell counts, kidney and liver function, and blood sugar, cholesterol, and triglyceride levels.
Afinitor/Votubia may cause fetal harm in pregnant women. Highly effective contraception is recommended for women
of child-bearing potential while receiving Afinitor/Votubia and for up to eight weeks after ending treatment. Women
taking Afinitor/Votubia should not breast feed. Fertility in women and men may be affected by treatment with
Afinitor/Votubia.
The most common adverse drug reactions (incidence >=10 percent) are mouth ulcers, skin rash, feeling tired or weak,
diarrhea, absence of menstrual periods, infections (including upper respiratory tract infection, sore throat and runny
nose, sinusitis, and pneumonia), nausea, decreased appetite, low level of red blood cells, high levels of cholesterol,
abnormal taste, acne, irregular menstrual periods, inflammation of lung tissue, high level of blood sugar, weight loss,
itching, swelling of extremities or other parts of the body, nose bleeds, and headache. The most common Grade 3-4
adverse drug reactions (incidence >=2 percent) are mouth ulcers, absence of menstrual periods, low level of red blood
cells, infections (including pneumonia), high level of blood sugar, feeling tired or weak, low white blood cells,
inflammation of lung tissue, diarrhea, and spontaneous bleeding or bruising. Cases of hepatitis B reactivation, blood
Novartis Pharma AG
CH-4002 Basel Switzerland
©Novartis 2015
May 2015
G-AFI-1113233
FOR MEDIA USE ONLY
clots in the lung or legs, and pneumocystis jirovecii pneumonia (PJP) have been reported. Abnormalities were
observed in hematology and clinical chemistry laboratory tests.
References
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AFINITOR summary of product characteristics. Basel, Switzerland: Novartis Pharma AG; 2013.
Motzer, R. et al. Renal-Cell Carcinoma. N Engl J Med. 1996; 335: 865-875.
National Cancer Institute. “Renal Cell Cancer PDQ.” Available at
http://www.cancer.gov/cancertopics/pdq/treatment/renalcell/patient. Accessed May 2015.
International Agency for Research on Cancer. Globocan 2012: Estimated Cancer Incidence, Mortality and Prevalence
Worldwide. Available at http://globocan.iarc.fr/pages/fact_sheets_population.aspx. Accessed May 2015.
Siegel, R et al. Cancer Statistics. CA Cancer J Clin. 2014;64:9–29.
National Cancer Institute. “Seer Stat Fact Sheets: Kidney and Renal Pelvis.” Available at
http://seer.cancer.gov/statfacts/html/kidrp.html#survival. Accessed May 2013.
American Cancer Society. “Targeted Therapies for Kidney Cancer.” Available at:
http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-treating-targeted-therapy. Accessed May
2015.
National Cancer Institute. “Dictionary of Cancer Terms.” Available at http://www.cancer.gov/dictionary/?CdrID=45563.
Accessed May 2015.
National Cancer Institute. “Inhibiting the PI3K/Akt/mTOR signaling pathway.” Available at
http://www.cancer.gov/cancertopics/understandingcancer/targetedtherapies/breastcancer_htmlcourse/page6#c. Accessed
May 2015.
Wullschleger S, Loewith R, Hall MN,TOR signaling in growth and metabolism. Cell. 2006;124:471-484.
Edinger AL, Thompson CB, Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake.Mol Biol
Cell. 2002;13:2276-2288.
Dancey JE. Inhibitors of the mammalian target of rapamycin. Expert Opin Investig Drugs. 2005; 14:313-328.
Humar R, Keifer FN, Berns H, Resink TJ, Battegay EJ. Hypoxia enhances vascular cell proliferation and angiogenesis in
vitro via rapamycin (mTOR) dependent signaling. FASEB J. 2002;16:771-780.
Afinitor global website. “AFINITOR Mechanism of Action.” Available at http://www.afinitor.com/global/afinitor-mechanismof-action.jsp. Accessed May 2015.
Motzer, et al. Phase 3 Trial of Everolimus for Metastatic Renal Cell Carcinoma: Final Results and Analysis of Prognostic
Factors. Cancer. 2010; 116: 4256-4265.
Data on file. Novartis Pharma AG. Basel, Switzerland.
Therase P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl
Cancer Inst. 2000;92:205-216.
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Novartis Pharma AG
CH-4002 Basel Switzerland
©Novartis 2015
May 2015
G-AFI-1113233