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Pfizer Receives FDA Approval for SUTENT® (sunitinib malate) as First and Only Adjuvant Treatment for Adult Patients at High Risk of Recurrent Renal Cell Carcinoma

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Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug
Administration has approved a new indication expanding the use of
SUTENT® (sunitinib malate) to include the adjuvant treatment of adult
patients at high risk of recurrent renal cell carcinoma (RCC) following
nephrectomy (surgical removal of the cancerous kidney). The approval was
based on results from the S-TRAC trial that demonstrated a significant
reduction in the risk of a disease-free survival (DFS) event (defined as
the interval between randomization and tumor recurrence, or secondary
primary cancer or death from any cause) for patients at high risk of RCC
recurrence who received SUTENT compared to placebo in the adjuvant
setting.

SUTENT has been a standard of care for the treatment of advanced RCC
since it was approved more than a decade ago, and is now the first
approved adjuvant treatment option for certain patients at high risk of
recurrent RCC - the most common type of kidney cancer. The current
treatment approach for RCC patients is surgery followed by observation,
which is suboptimal for patients at high risk of recurrence.

"Today's approval marks an important step forward for the treatment of
adult patients who are at high risk of their renal cell carcinoma
returning after surgery," said Liz Barrett, global president and general
manager, Pfizer Oncology. "Pfizer has been dedicated to advancing the
science of RCC treatment for over a decade, and we are pleased to see
this commitment continue to translate into meaningful options for
patients."

The S-TRAC trial was 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 recurrent RCC
following nephrectomy. The study met its primary endpoint of improving
DFS and the results were published by The New England Journal of
Medicine
in October 2016.

"Some patients who have undergone surgery for locally advanced RCC are
at high risk of recurrence and often fear their disease returning," said
Daniel George, MD, study investigator and medical oncologist at Duke
University Medical Center. "This adjuvant therapy is the
first-of-its-kind and a remarkable clinical development for these
patients who before today, have been restricted to a wait and see
approach."

In the S-TRAC trial, the Hazard Ratio (HR) was 0.76 (95% CI: 0.59, 0.98)
with a 2-sided p-value=0.03 in favor of SUTENT, representing a
statistically significant 24% relative reduction in the risk of a DFS
event. The median DFS was 6.8 years (95% CI: 5.8, not reached [NR]) in
the SUTENT arm compared with 5.6 years (95% CI: 3.8, 6.6) in the placebo
arm. At five years, the DFS rate for patients receiving SUTENT was 59.3%
and 51.3% for placebo. This represents a persistent 8% absolute benefit.

No new safety signals were identified in the S-TRAC trial. The most
common adverse reactions occurring in ≥20% of patients receiving SUTENT
for adjuvant treatment of RCC (all grades) were mucositis/stomatitis
(61%), fatigue/asthenia (57%), diarrhea (57%), hand-foot syndrome (50%),
hypertension (39%), altered taste (38%), nausea (34%), dyspepsia (27%),
abdominal pain (25%), rash (24%), hypothyroidism/TSH increased (24%),
bleeding events, all sites (24%), and hair color changes (22%). The
prescribing information for SUTENT also includes a boxed warning for
hepatotoxicity and notes the following warnings and precautions:
cardiovascular events; QT Interval Prolongation and Torsades de Pointes;
hypertension; hemorrhagic events and viscus perforation; Tumor Lysis
Syndrome (TLS); thrombotic microangiopathy (TMA); proteinuria;
dermatologic toxicities; thyroid dysfunction; hypoglycemia;
osteonecrosis of the jaw (ONJ); wound healing; and embryo-fetal
toxicity. For more information, including Boxed Warning, please see the
Important Safety Information for SUTENT below.

SUTENT Important Safety Information

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
syndrome.

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
3-4.

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%), mucositis/stomatitis
(6% vs 0%), and hypertension (8% vs 1%).

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%).

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

About Renal Cell Carcinoma (RCC)

Each year, approximately 304,000 new cases of kidney cancer are
diagnosed worldwide, representing approximately 2-3 percent of all
cancers.1,2,3 Renal cell carcinoma (RCC) is the most common
type of kidney cancer, accounting for around 90 percent of cases.4
Approximately 75 percent of patients with clear cell RCC are
non-metastatic, and 70-80 percent will have a nephrectomy with curative
intent, or surgical removal of the tumor.5 Patients at high
risk of recurrence represent approximately 15 percent of all patients
with primary resected RCC and approximately 60 percent of these patients
will recur and develop metastatic disease within five years.6

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).

Now approved in 119 countries across diagnoses, more than 350,000
patients worldwide have been treated with SUTENT.7 SUTENT is
supported by an extensive body of evidence in scientific literature,
including more than 440 publications.

About Pfizer Oncology

Pfizer Oncology is committed to pursuing innovative treatments that have
a meaningful impact on those living with cancer. As a leader in oncology
speeding cures and accessible breakthrough medicines to patients, Pfizer
Oncology is helping to redefine life with cancer. Our strong pipeline of
biologics, small molecules and immunotherapies, one of the most robust
in the industry, is studied with precise focus on identifying and
translating the best scientific breakthroughs into clinical application
for patients across a wide range of cancers. By working collaboratively
with academic institutions, individual researchers, cooperative research
groups, governments and licensing partners, Pfizer Oncology strives to
cure or control cancer with its breakthrough medicines. Because Pfizer
Oncology knows that success in oncology is not measured solely by the
medicines you manufacture, but rather by the meaningful partnerships you
make to have a more positive impact on people's lives.

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,
prevention, treatments and cures that challenge the most feared diseases
of our time. Consistent with our responsibility as one of the world's
premier innovative biopharmaceutical companies, we collaborate with
health care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world. For
more than 150 years, we have worked to make a difference for all who
rely on us. We routinely post information that may be important to
investors on our website at www.pfizer.com.
In addition, to learn more, please visit us on www.pfizer.com
and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube
and like us on Facebook at Facebook.com/Pfizer.

DISCLOSURE NOTICE: The information contained in this release is
current as of November 16, 2017. 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 malate) and a 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 new
indication; the uncertainties inherent in research and development, as
well as 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 new
indication may be filed in any other jurisdictions; 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, 2016 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
www.sec.gov
and www.pfizer.com.

_________________________

1 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: http://globocan.iarc.fr(link
is external)
. Accessed September 2016.

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

3 World Cancer Research Fund International: Kidney
Cancer statistics. Available from: http://www.wcrf.org/int/cancer-facts-figures/data-specific-cancers/kidney-cancer-statistics.
Accessed March 2016.

4 What is Kidney Cancer. James Whale Fund for Kidney
Cancer. Available at: http://www.jameswhalefund.org/kidneycancer/what-is-kidney-cancer/(link
is external)
. Accessed September 2016.

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

6 Wheler J, Johnson M, Seidman A. Adjuvant therapy with
aromatase inhibitors for postmenopausal women with early breast
cancer: evidence and ongoing controversy. Semin Oncol; 2006;
33(6): 672-80.

7 Pfizer Data on File.

 

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