Market Overview

Pfizer Announces Update on European Marketing Authorization Application for SUTENT® (sunitinib) in Adult Patients at High Risk of Recurrent Renal Cell Carcinoma


Pfizer Inc. (NYSE:PFE) today announced that the Committee for Medicinal
Products for Human Use (CHMP) of the European Medicines Agency (EMA) has
recommended against expanding use of SUTENT® (sunitinib) to include the
adjuvant treatment of adult patients at a high risk of recurrent renal
cell carcinoma (RCC) following nephrectomy (surgical removal of the
cancerous kidney). The CHMP's recommendation is not binding but will now
be taken into consideration by the European Commission (EC). There is
currently no approved adjuvant treatment option available for patients
with non-metastatic RCC at high risk for recurrence in the European
Union (EU).

In the U.S., SUTENT is approved for the adjuvant treatment of adult
patients at high risk of recurrent RCC following nephrectomy.

"We remain confident in the potential of SUTENT for RCC patients at high
risk of their cancer returning after surgery who today are restricted to
a wait and see, or more accurately, a wait and worry approach," said
Mace Rothenberg, MD, chief development officer, Oncology, Pfizer Global
Product Development. "We will continue to work closely with the European
Medicines Agency as they complete their review and render a decision on
this application."

On November 16, 2017, the U.S. Food and Drug Administration approved an
expanded indication for SUTENT as the first treatment for adult patients
at high risk of recurrence following nephrectomy. The FDA expanded
indication was based on results from the S-TRAC trial, a multicenter,
international, randomized, double-blind, placebo-controlled Phase 3
trial of SUTENT versus placebo in 615 patients with clear cell histology
and high risk of recurrence following nephrectomy. The results were
published by The New England Journal of Medicine in October 2016.

Each year, approximately 338,000 new cases of kidney cancer are
diagnosed worldwide, representing approximately 2-3 percent of all
cancers.1,2,3 Approximately 75 percent of patients with clear
cell RCC are non-metastatic, and 70-80 percent will have a nephrectomy
with curative intent.4 Patients at high risk of recurrence
represent approximately 10 percent of all patients with primary resected
RCC and approximately 60 percent of these patients will recur and
develop metastatic disease within five years.5

Pfizer is dedicated to addressing the unmet needs of patients and has
been advancing the science of RCC for the last decade through research
into established and novel compounds. Our near-term areas of focus
include expanding access of our marketed products, exploration of
biomarkers to better personalize therapy and immunotherapy combinations.

SUTENT Important Safety Information

Boxed Warning/Hepatotoxicity has been observed in clinical trials and
postmarketing experience. Hepatotoxicity may be severe, and in some
cases fatal. Monitor hepatic function and interrupt, reduce, or
discontinue dosing as recommended.
Fatal liver failure has been
observed. Monitor liver function tests before initiation of treatment,
during each cycle of treatment, and as clinically indicated. Interrupt
SUTENT for Grade 3 or 4 drug-related hepatic adverse reactions and
discontinue if there is no resolution. Do not restart SUTENT if patients
subsequently experience severe changes in liver function tests or have
signs and symptoms of liver failure.

Cardiovascular events, including myocardial ischemia, myocardial
infarction, left ventricular ejection fraction declines to below the
lower limit of normal and cardiac failure including death have occurred.
Monitor patients for signs and symptoms of congestive heart failure.
Discontinue SUTENT for clinical manifestations of congestive heart
failure. In patients without cardiac risk factors, a baseline evaluation
of ejection fraction should be considered. Baseline and periodic
evaluations of left ventricular ejection fraction should also be
considered while these patients are receiving SUTENT.

SUTENT can cause QT Prolongation in a dose-dependent manner,
which may lead to an increased risk for ventricular arrhythmias
including Torsades de Pointes, which has been seen in <0.1% of
patients. Monitor patients that are at a higher risk for developing QT
interval prolongation, including those with a history of QT interval
prolongation, patients who are taking antiarrhythmics, or patients with
relevant pre-existing cardiac disease, bradycardia, or electrolyte
disturbances. Consider monitoring of electrocardiograms and
electrolytes. Concomitant treatment with strong CYP3A4 inhibitors may
increase sunitinib plasma concentrations and dose reduction of SUTENT
should be considered.

Hypertension may occur. Monitor blood pressure and treat as
needed with standard antihypertensive therapy. In cases of severe
hypertension, temporary suspension of SUTENT is recommended until
hypertension is controlled.

Hemorrhagic events, including tumor-related hemorrhage, and
viscus perforation (both with fatal events) have occurred. These events
may occur suddenly, and in the case of pulmonary tumors, may present as
severe and life-threatening hemoptysis or pulmonary hemorrhage. Perform
serial complete blood counts (CBCs) and physical examinations.

Cases of tumor lysis syndrome (TLS) (some fatal) have been
reported. Patients generally at risk of TLS are those with high tumor
burden prior to treatment. Monitor these patients closely and treat as
clinically indicated.

Thrombotic microangiopathy (TMA), including thrombotic
thrombocytopenic purpura and hemolytic uremic syndrome, sometimes
leading to renal failure or a fatal outcome, has been reported in
patients who received SUTENT as monotherapy and in combination with
bevacizumab. Discontinue SUTENT in patients developing TMA. Reversal of
the effects of TMA has been observed after treatment was discontinued.

Proteinuria and nephrotic syndrome have been reported. Some of
these cases have resulted in renal failure and fatal outcomes. Monitor
patients for the development or worsening of proteinuria. Perform
baseline and periodic urinalysis during treatment, with follow-up
measurement of 24-hour urine protein as clinically indicated. Interrupt
treatment for 24-hour urine protein ≥3 grams. Discontinue for repeat
episodes of protein ≥3 grams despite dose reductions or nephrotic

Dermatologic toxicities: Severe cutaneous reactions have been
reported, including cases of necrotizing fasciitis, erythema multiforme
(EM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis
(TEN), some of which were fatal. If signs or symptoms of EM, SJS, or TEN
are present, discontinue SUTENT treatment. If a diagnosis of SJS or TEN
is suspected, treatment must not be re-started.

Necrotizing fasciitis, including fatal cases, has been reported,
including of the perineum and secondary to fistula formation.
Discontinue SUTENT in patients who develop necrotizing fasciitis.

Thyroid dysfunction may occur. Monitor thyroid function in
patients with signs and/or symptoms suggestive of thyroid dysfunction,
including hypothyroidism, hyperthyroidism, and thyroiditis, and treat
per standard medical practice.

Hypoglycemia may occur. SUTENT can result in symptomatic
hypoglycemia, which may lead to a loss of consciousness or require
hospitalization. Reductions in blood glucose levels may be worse in
patients with diabetes. Check blood glucose levels regularly during and
after discontinuation of treatment with SUTENT. Assess if antidiabetic
drug dosage needs to be adjusted to minimize the risk of hypoglycemia.

Osteonecrosis of the jaw (ONJ) has been reported. Consider
preventive dentistry prior to treatment with SUTENT. If possible, avoid
invasive dental procedures, particularly in patients receiving
intravenous bisphosphonate therapy.

Impaired wound healing has occurred with SUTENT. Temporary
interruption of therapy with SUTENT is recommended in patients
undergoing major surgical procedures. There is limited clinical
experience regarding the timing of reinitiation of therapy following
major surgical intervention. Therefore, the decision to resume SUTENT
therapy following a major surgical intervention should be based upon
clinical judgment of recovery from surgery.

Embryo fetal toxicity and reproductive potential

Females - SUTENT can cause fetal harm when administered to
pregnant women. Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective contraception
during treatment with SUTENT and for 4 weeks following the final dose.

Males - Based on findings in animal reproduction studies, advise
male patients with female partners of reproductive potential to use
effective contraception during treatment with SUTENT and for 7 weeks
after the last dose.

Male and female infertility - based on findings in animals, male
and female fertility may be compromised by treatment with SUTENT

Lactation: Because of the potential for serious adverse reactions
in breastfed infants from SUTENT, advise a lactating woman not to
breastfeed during treatment with SUTENT and for at least 4 weeks after
the last dose.

Venous thromboembolic events: In patients treated with SUTENT
(N=7527) for GIST, advanced RCC, adjuvant treatment of RCC and pNET,
3.5% of patients experienced a venous thromboembolic event; 2.2% Grade

There have been (<1%) reports, some fatal, of subjects presenting with
seizures and radiological evidence of reversible posterior
leukoencephalopathy syndrome (RPLS).
Patients with seizures and
signs/symptoms consistent with RPLS, such as hypertension, headache,
decreased alertness, altered mental functioning, and visual loss,
including cortical blindness, should be controlled with medical
management including control of hypertension. Temporary suspension of
SUTENT is recommended; following resolution, treatment may be resumed at
the discretion of the treating healthcare provider.

Pancreatic function: In a trial of patients receiving adjuvant
treatment for RCC, 1 patient (<1%) on SUTENT and none on placebo
experienced pancreatitis.

CYP3A4 inhibitors and inducers: Dose adjustments are recommended
when SUTENT is administered with CYP3A4 inhibitors or inducers. During
treatment with SUTENT, patients should not drink grapefruit juice, eat
grapefruit, or take St. John's Wort.

Most common ARs & most common grade 3/4 ARs (adjuvant RCC):
The most common ARs reported in ≥20% of patients receiving SUTENT for
adjuvant treatment of RCC and more commonly than in patients given
placebo (all grades, vs placebo) were mucositis/stomatitis (61% vs 15%),
diarrhea (57% vs 22%), fatigue/asthenia (57% vs 34%), hand-foot syndrome
(50% vs 10%), hypertension (39% vs 14%), altered taste (38% vs 6%),
nausea (34% vs 15%), dyspepsia (27% vs 7%), abdominal pain (25% vs 9%),
hypothyroidism/TSH increased (24% vs 4%), rash (24% vs 12%), hair color
changes (22% vs 2%). The most common grade 3/4 ARs reported in
≥5% of patients receiving SUTENT for adjuvant treatment of RCC and more
commonly than in patients given placebo (vs placebo) were hand-foot
syndrome (16% vs <1%), fatigue/asthenia (8% vs 2%), hypertension (8% vs
1%), and mucositis/stomatitis (6% vs 0%).

Most common grade 3/4 lab abnormalities (adjuvant RCC): The most
common grade 3/4 lab abnormalities
(occurring in ≥ 2% of patients
receiving SUTENT) included neutropenia (13%), thrombocytopenia (5%),
leukopenia (3%), lymphopenia (3%), elevated alanine aminotransferase
(2%), elevated aspartate aminotransferase (2%), hyperglycemia (2%), and
hyperkalemia (2%).

Most common ARs & most common grade 3/4 ARs (advanced RCC):
The most common ARs reported in ≥20% of patients receiving SUTENT for
treatment-naïve metastatic RCC (all grades, vs IFNα) were diarrhea (66%
vs 21%), fatigue (62% vs 56%), nausea (58% vs 41%), anorexia (48% vs
42%), altered taste (47% vs 15%), mucositis/stomatitis (47% vs 5%), pain
in extremity/limb discomfort (40% vs 30%), vomiting (39% vs 17%),
bleeding, all sites (37% vs 10%), hypertension (34% vs 4%), dyspepsia
(34% vs 4%), arthralgia (30% vs 19%), abdominal pain (30% vs 12%), rash
(29% vs 11%), hand-foot syndrome (29% vs 1%), back pain (28% vs 14%),
cough (27% vs 14%), asthenia (26% vs 22%), dyspnea (26% vs 20%), skin
discoloration/yellow skin (25% vs 0%), peripheral edema (24% vs 5%),
headache (23% vs 19%), constipation (23% vs 14%), dry skin (23% vs 7%),
fever (22% vs 37%), and hair color changes (20% vs <1%). The most common
grade 3/4 ARs reported in ≥5% of patients with RCC receiving SUTENT (vs
IFNα) were fatigue (15% vs 15%), hypertension (13% vs <1%), asthenia
(11% vs 6%), diarrhea (10% vs <1%), hand-foot syndrome (8% vs 0%),
dyspnea (6% vs 4%), nausea (6% vs 2%), back pain (5% vs 2%), pain in
extremity/limb discomfort (5% vs 2%), vomiting (5% vs 1%), and abdominal
pain (5% vs 1%).

Most common grade 3/4 lab abnormalities (advanced RCC): The most
common grade 3/4 lab abnormalities (occurring in ≥5% of patients with
RCC receiving SUTENT vs IFNα) included lymphocytes (18% vs 26%), lipase
(18% vs 8%), neutrophils (17% vs 9%), uric acid (14% vs 8%), platelets
(9% vs 1%), hemoglobin (8% vs 5%), sodium decreased (8% vs 4%),
leukocytes (8% vs 2%), glucose increased (6% vs 6%), phosphorus (6% vs
6%), and amylase (6% vs 3%).

Most common ARs & most common grade 3/4 ARs (imatinib-resistant or
-intolerant GIST):
The most common ARs reported in ≥20% of patients
with GIST and more commonly with SUTENT than placebo (all grades, vs
placebo) were diarrhea (40% vs 27%), anorexia (33% vs 29%), skin
discoloration (30% vs 23%), mucositis/stomatitis (29% vs 18%), asthenia
(22% vs 11%), altered taste (21% vs 12%), and constipation (20% vs 14%).
The most common grade 3/4 ARs reported in ≥4% of patients with GIST
receiving SUTENT (vs placebo) were asthenia (5% vs 3%), hand-foot
syndrome (4% vs 3%), diarrhea (4% vs 0%), and hypertension (4% vs 0%).

Most common grade 3/4 lab abnormalities (imatinib-resistant or
-intolerant GIST):
The most common grade 3/4 lab abnormalities
(occurring in ≥5% of patients with GIST receiving SUTENT vs placebo)
included lipase (10% vs 7%), neutrophils (10% vs 0%), amylase (5% vs
3%), and platelets (5% vs 0%).

Most common ARs & most common grade 3/4 ARs (advanced pNET):
The most common ARs reported in ≥20% of patients with advanced pNET and
more commonly with SUTENT than placebo (all grades, vs placebo) were
diarrhea (59% vs 39%), stomatitis/oral syndromes (48% vs 18%), nausea
(45% vs 29%), abdominal pain (39% vs 34%), vomiting (34% vs 31%),
asthenia (34% vs 27%), fatigue (33% vs 27%), hair color changes (29% vs
1%), hypertension (27% vs 5%), hand-foot syndrome (23% vs 2%), bleeding
events (22% vs 10%), epistaxis (21% vs 5%), and dysgeusia (21% vs 5%).
The most common grade 3/4 ARs reported in ≥5% of patients with advanced
pNET receiving SUTENT (vs placebo) were hypertension (10% vs 1%),
hand-foot syndrome (6% vs 0%), stomatitis/oral syndromes (6% vs 0%),
abdominal pain (5% vs 10%), fatigue (5% vs 9%), asthenia (5% vs 4%), and
diarrhea (5% vs 2%).

The most common grade 3/4 lab abnormalities (advanced pNET)
included decreased neutrophils (16% vs 0%), increased glucose (12% vs
18%), increased alkaline phosphatase (10% vs 11%), decreased phosphorus
(7% vs 5%), decreased lymphocytes (7% vs 4%), increased creatinine (5%
vs 5%), increased lipase (5% vs 4%), increased AST (5% vs 3%), and
decreased platelets (5% vs 0%).

Please see full Prescribing Information, including BOXED WARNING and
Medication Guide, for SUTENT® (sunitinib malate) at

About SUTENT® (sunitinib malate)

Sunitinib is a small molecule that inhibits multiple receptor tyrosine
kinases, some of which are implicated in tumor growth, pathologic
angiogenesis, and metastatic progression of cancer. Sunitinib was
evaluated for its inhibitory activity against a variety of kinases (>80
kinases) and was identified as an inhibitor of platelet-derived growth
factor receptors (PDGFRα and PDGFRβ), vascular endothelial growth factor
receptors (VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT),
Fms-like tyrosine kinase-3 (FLT3), colony stimulating factor receptor
Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor
receptor (RET).

SUTENT is indicated in the U.S. for the treatment of gastrointestinal
stromal tumor (GIST) after disease progression on or intolerance to
imatinib mesylate; the treatment of advanced renal cell carcinoma (RCC);
the adjuvant treatment of adult patients at high risk of recurrent RCC
following nephrectomy; the treatment of progressive, well-differentiated
pancreatic neuroendocrine tumors (pNET) in patients with unresectable
locally advanced or metastatic disease.

About Pfizer Oncology

Pfizer Oncology is committed to pursuing innovative treatments that have
a meaningful impact on people living with cancer. Our growing pipeline
of biologics, small molecules, and immunotherapies is focused on
identifying and translating the best scientific breakthroughs into
clinical application for patients across a diverse array of solid tumors
and hematologic cancers. Today, we have 10 approved oncology medicines
and 17 assets currently in clinical development. By maximizing our
internal scientific resources and collaborating with other companies,
government and academic institutions, as well as non-profit and
professional organizations, we are bringing together the brightest and
most enterprising minds to take on the toughest cancers. Together we can
accelerate breakthrough treatments to patients around the world and work
to redefine life with cancer.

Pfizer Inc.: Working together for a healthier worldTM

At Pfizer, we apply science and our global resources to bring therapies
to people that extend and significantly improve their lives. We strive
to set the standard for quality, safety and value in the discovery,
development and manufacture of health care products. Our global
portfolio includes medicines and vaccines as well as many of the world's
best-known consumer health care products. Every day, Pfizer colleagues
work across developed and emerging markets to advance wellness,
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DISCLOSURE NOTICE: The information contained in this release is
current as of February 23, 2018. Pfizer assumes no obligation to update
forward-looking statements contained in this release as the result of
new information or future events or developments.

This release contains forward-looking information about SUTENT
(sunitinib), Pfizer's oncology portfolio and a potential new indication
for SUTENT for the adjuvant treatment of adult patients at high risk of
recurrent renal cell carcinoma following nephrectomy, including their
potential benefits, that involves substantial risks and uncertainties
that could cause actual results to differ materially from those
expressed or implied by such statements. Risks and uncertainties
include, among other things, uncertainties regarding the commercial
success of SUTENT in the potential new indication; the uncertainties
inherent in research and development, including the possibility of
unfavorable clinical trial results, including unfavorable new clinical
data and additional analyses of existing clinical data; whether and when
applications for SUTENT for the potential new indication may be filed in
any other jurisdictions; whether and when the European Commission will
approve the Marketing Authorization Application for SUTENT for the
potential new indication and whether and when any such other
applications may be approved by regulatory authorities, which will
depend on the assessment by such regulatory authorities of the
benefit-risk profile suggested by the totality of the efficacy and
safety information submitted; decisions by regulatory authorities
regarding labeling and other matters that could affect the availability
or commercial potential of SUTENT; and competitive developments.

A further description of risks and uncertainties can be found in
Pfizer's Annual Report on Form 10-K for the fiscal year ended December
31, 2017 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned "Risk Factors" and "Forward-Looking
Information and Factors That May Affect Future Results," as well as in
its subsequent reports on Form 8-K, all of which are filed with the U.S.
Securities and Exchange Commission and available at

1 World Cancer Research Fund International: Kidney Cancer
statistics. Available from:
Accessed February 2018.

2 Ljungberg B, Campbell S and Choi H. The Epidemiology of
Renal Cell Carcinoma. Eur Urol. 2011;60:615-621.

3 Ferlay J, Shin HR, Bray F.GLOBOCAN 2008 v1.2, Cancer
Incidence and Mortality Worldwide: IARC CancerBase No. 10 Lyon, France:
International Agency for Research on Cancer; 2010. Available at:
(link is external)
. Accessed February 2018.

4 Based on comparison between 2015 Swedish population study
(76%), Navigant interviews (95%), and Quant Pulse (79%). 2018-2022.

5 Pfizer. Data on file. 2018.

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