20 abstracts across multiple tumor types;
unique mechanisms of action address the diverse needs of people
living with cancer
New combination study data in renal cell
carcinoma and first-in-human results for OX40 agonist provide new
insights in immuno-oncology
Pfizer Inc. (NYSE:PFE) today announced that it will be
presenting data from 20 abstracts, including three late-breakers,
at the European Society for Medical Oncology (ESMO) 2016 Congress
in Copenhagen from October 7-11, 2016. The presentations
demonstrate progress addressing cancer’s complex challenges through
our work across 11 tumor types and eight distinct mechanisms of
action, including two immuno-oncology/targeted therapy combination
studies in renal cell carcinoma (RCC).
“Pfizer looks forward to sharing news from our diverse and
growing oncology portfolio, particularly in the area of novel
immunotherapies and combination approaches,” said Liz Barrett,
global president and general manager, Pfizer Oncology. “We are also
particularly pleased to present new data from our RCC franchise,
where Pfizer has established itself as a leader in driving
meaningful progress through significant contributions in RCC
research and development.”
Pfizer will present data from three late-breaker abstracts at
this year’s ESMO, including results from the S-TRAC clinical trial
(Sunitinib Trial in Adjuvant Renal Cancer), a Phase 3 study of
SUTENT® (sunitinib) versus placebo in the adjuvant setting, during
a Presidential Symposium. Other late-breakers include early data
from a Phase 1 study of PF-06647020, a novel antibody-drug
conjugate (ADC) candidate targeting PTK7, a receptor tyrosine
kinase associated with poorer prognosis that is expressed in many
tumor types, and a biomarker analysis from the Phase 3 PALOMA-2
trial of IBRANCE® (palbociclib) in combination with letrozole in
postmenopausal women with estrogen receptor-positive, human
epidermal growth factor 2-negative (ER+/HER2–) metastatic breast
cancer. These data for IBRANCE as well as health-related quality of
life data from PALOMA-2 being presented as a poster discussion add
to the growing body of evidence supporting the use of IBRANCE in
this patient population.
Among six abstracts selected for poster discussion presentation
at the meeting, four will address development efforts from Pfizer’s
growing immuno-oncology pipeline. Highlights include data from two
advanced RCC studies of INLYTA® (axitinib) in combination with
different checkpoint inhibitors, including one study in combination
with avelumab, an anti-PD-L1 IgG1 monoclonal antibody being
developed through an Alliance between Pfizer and Merck KGaA,
Darmstadt, Germany. Pfizer will also present the latest safety,
anti-tumor activity and biomarker data from the first-in-human
single-agent study of Pfizer’s investigational immunotherapy
PF-04518600, an OX40 agonist, in a variety of advanced cancers.
These preliminary results evaluating 25 patients suggest that
PF-04518600 is tolerated up to 3 mg/kg and showed early anti-tumor
activity.
Additionally, an updated data set from PROFILE 1001, a
multicenter, single-arm Phase 1 study that examined use of XALKORI®
(crizotinib) in patients with ROS1-positive advanced non-small cell
lung cancer (NSCLC), will be presented. This analysis was used to
support the recent approval of XALKORI in the European Union for
patients with advanced NSCLC whose tumors are ROS1-positive.
A full list of the Pfizer-sponsored late-breaker and poster
discussions at ESMO is included below.
Pfizer-sponsored late-breakers at ESMO include:
Abstract
Number/Title/Presenter
Presentation Type
Date/Time (All Times
CEST)
Location (Abstract LBA11_PR) Phase III
trial of sunitinib (SU) vs placebo (PBO) as adjuvant treatment for
high-risk renal cell carcinoma (RCC) after nephrectomy (S-TRAC)
Ravaud A
Presidential Symposium Monday, October
10
16:30-18:10
Copenhagen
(Abstract LBA15) Biomarker analyses
from the Phase 3 PALOMA-2 trial of palbociclib (P) with letrozole
(L) compared with placebo (PLB) plus L in postmenopausal women with
ER+/HER2- advanced breast cancer (ABC)
Finn R
Proffered Paper Saturday, October 8
11:00-12:30
Vienna
(Abstract LBA35) A Phase 1 study of
PF-06647020, an antibody-drug conjugate (ADC) targeting protein
tyrosine kinase 7 (PTK7), in patients with advanced solid tumors
including platinum resistant ovarian cancer (OVCA)
Sachdev J
Poster Discussion Saturday, October 8
9:30-10:30
Bern
Pfizer-sponsored poster discussions at ESMO include:
Abstract Number/Title/Presenter
Date/Time (All Times
CEST)
Location (Abstract 1206PD) Crizotinib in
advanced ROS1-rearranged non-small cell lung cancer (NSCLC):
updated results from PROFILE 1001
Shaw A
Sunday, October 9
14:45-16:15
Oslo
(Abstract 225PD) Impact of palbociclib plus
letrozole on health related quality of life (HRQOL) compared with
letrozole alone in treatment naïve postmenopausal patients with ER+
HER2- metastatic breast cancer (MBC): results from PALOMA-2
Rugo H
Sunday, October 9
16:30-17:30
Brussels
(Abstract 773PD) Axitinib in combination
with pembrolizumab in patients (pts) with advanced renal cell
carcinoma (aRCC): preliminary safety and efficacy results
Atkins M
Sunday, October 9
16:30-17:30
Athens
(Abstract 775PD) Phase 1b dose-finding
study of avelumab (anti-PD-L1) + axitinib in treatment-naïve
patients with advanced renal cell carcinoma
Larkin J
Sunday, October 9
16:30-17:30
Athens
(Abstract 777PD) Avelumab (MSB0010718C;
anti-PD-L1) in patients with metastatic urothelial carcinoma
progressed after platinum-based therapy or platinum ineligible
Patel M
Sunday, October 9
16:30-17:30
Athens
(Abstract 1053PD) A first-in-human (FIH)
study of PF-04518600 (PF-8600) OX40 agonist in adult patients (pts)
with select advanced malignancies
Diab A
Monday, October 10
9:30-10:30
Berlin
For a complete list of Pfizer-sponsored abstracts featuring data
on our broad oncology pipeline of biologics, small molecules and
immunotherapies, please visit:
http://www.pfizer.com/files/news/esmo/Pfizer_Oncology_Data_Presentations_at_ESMO_2016.pdf
Learn more about how Pfizer Oncology is applying innovative
approaches to improve the outlook for people living with cancer at
http://www.pfizer.com/research/therapeutic_areas/oncology.
About IBRANCE® (palbociclib)
IBRANCE is an oral inhibitor of cyclin dependent kinases (CDKs)
4 and 6,i which are key regulators of the cell cycle that trigger
cellular progression.ii,iii In the U.S., IBRANCE is indicated for
the treatment of hormone receptor-positive (HR+), HER2- advanced or
metastatic breast cancer in combination with letrozole as initial
endocrine based therapy in postmenopausal women, or fulvestrant in
women with disease progression following endocrine therapy.i The
indication in combination with letrozole is approved under
accelerated approval based on progression-free survival (PFS).
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in a confirmatory
trial.i
IBRANCE Important Safety Information
Neutropenia was the most frequently reported adverse
reaction in Study 1 (PALOMA-1) (75%) and Study 2 (PALOMA-3) (83%).
In Study 1, Grade 3 (57%) or 4 (5%) decreased neutrophil counts
were reported in patients receiving IBRANCE plus letrozole. In
Study 2, Grade 3 (56%) or Grade 4 (11%) decreased neutrophil counts
were reported in patients receiving IBRANCE plus fulvestrant.
Febrile neutropenia has been reported in about 1% of patients
exposed to IBRANCE. One death due to neutropenic sepsis was
observed in Study 2. Inform patients to promptly report any
fever.
Monitor complete blood count prior to starting IBRANCE, at the
beginning of each cycle, on Day 14 of first 2 cycles, and as
clinically indicated. Dose interruption, dose reduction, or delay
in starting treatment cycles is recommended for patients who
develop Grade 3 or 4 neutropenia.
Pulmonary embolism (PE) has been reported at a higher
rate in patients treated with IBRANCE plus letrozole in Study 1
(5%) and in patients treated with IBRANCE plus fulvestrant in Study
2 (1%) compared with no cases in patients treated either with
letrozole alone or fulvestrant plus placebo. Monitor for signs and
symptoms of PE and treat as medically appropriate.
Based on the mechanism of action, IBRANCE can cause fetal
harm. Advise females of reproductive potential to use effective
contraception during IBRANCE treatment and for at least 3 weeks
after the last dose. IBRANCE may impair fertility in males
and has the potential to cause genotoxicity. Advise male patients
with female partners of reproductive potential to use effective
contraception during IBRANCE treatment and for 3 months after the
last dose. Advise females to inform their healthcare provider of a
known or suspected pregnancy. Advise women not to breastfeed
during IBRANCE treatment and for 3 weeks after the last dose
because of the potential for serious adverse reactions in nursing
infants.
The most common adverse reactions (≥10%) of any
grade reported in Study 1 of IBRANCE plus letrozole vs
letrozole alone included neutropenia (75% vs 5%), leukopenia (43%
vs 3%), fatigue (41% vs 23%), anemia (35% vs 7%), upper respiratory
infection (31% vs 18%), nausea (25% vs 13%), stomatitis (25% vs
7%), alopecia (22% vs 3%), diarrhea (21% vs 10%), thrombocytopenia
(17% vs 1%), decreased appetite (16% vs 7%), vomiting (15% vs 4%),
asthenia (13% vs 4%), peripheral neuropathy (13% vs 5%), and
epistaxis (11% vs 1%).
Grade 3/4 adverse reactions (≥10%) in Study 1
reported at a higher incidence in the IBRANCE plus letrozole group
vs the letrozole alone group included neutropenia (54% vs 1%) and
leukopenia (19% vs 0%). The most frequently reported serious
adverse events in patients receiving IBRANCE plus letrozole were
pulmonary embolism (4%) and diarrhea (2%).
Lab abnormalities occurring in Study 1 (all
grades, IBRANCE plus letrozole vs letrozole alone) were decreased
WBC (95% vs 26%), decreased neutrophils (94% vs 17%), decreased
lymphocytes (81% vs 35%), decreased hemoglobin (83% vs 40%), and
decreased platelets (61% vs 16%).
The most common adverse reactions (≥10%) of any grade
reported in Study 2 of IBRANCE plus fulvestrant vs
fulvestrant plus placebo included neutropenia (83% vs 4%),
leukopenia (53% vs 5%), infections (47% vs 31%), fatigue (41% vs
29%), nausea (34% vs 28%), anemia (30% vs 13%), stomatitis (28% vs
13%), headache (26% vs 20%), diarrhea (24% vs 19%),
thrombocytopenia (23% vs 0%), constipation (20% vs 16%), vomiting
(19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased
appetite (16% vs 8%), and pyrexia (13% vs 5%).
Grade 3/4 adverse reactions (≥10%) in Study 2
reported at a higher incidence in the IBRANCE plus fulvestrant
group vs the fulvestrant plus placebo group included neutropenia
(66% vs 1%) and leukopenia (31% vs 2%). The most frequently
reported serious adverse reactions in patients receiving IBRANCE
plus fulvestrant were infections (3%), pyrexia (1%), neutropenia
(1%), and pulmonary embolism (1%).
Lab abnormalities occurring in Study 2 (all
grades, IBRANCE plus fulvestrant vs fulvestrant plus placebo) were
decreased WBC (99% vs 26%), decreased neutrophils (96% vs 14%),
anemia (78% vs 40%), and decreased platelets (62% vs 10%).
Avoid concurrent use of strong CYP3A inhibitors. If
patients must be administered a strong CYP3A inhibitor, reduce the
IBRANCE dose to 75 mg/day. If the strong inhibitor is discontinued,
increase the IBRANCE dose (after 3-5 half-lives of the inhibitor)
to the dose used prior to the initiation of the strong CYP3A
inhibitor. Grapefruit or grapefruit juice may increase plasma
concentrations of IBRANCE and should be avoided. Avoid concomitant
use of strong CYP3A inducers. The dose of sensitive CYP3A
substrates with a narrow therapeutic index may need to be
reduced as IBRANCE may increase their exposure.
IBRANCE has not been studied in patients with moderate
to severe hepatic impairment or in patients with severe
renal impairment (CrCl <30 mL/min).
The full prescribing information for IBRANCE can be found at
www.pfizer.com.
About INLYTA® (axitinib)
INLYTA, a kinase inhibitor, is an oral therapy that is designed
to inhibit tyrosine kinases, including vascular endothelial growth
factor (VEGF) receptors 1, 2 and 3; these receptors can influence
tumor growth, vascular angiogenesis and progression of cancer (the
spread of tumors). In the U.S., INLYTA is approved for the
treatment of advanced renal cell carcinoma (RCC) after failure of
one prior systemic therapy.
INLYTA Important Safety Information
Hypertension including hypertensive crisis has been observed.
Blood pressure should be well controlled prior to initiating
INLYTA. Monitor for hypertension and treat as needed. For
persistent hypertension, despite use of antihypertensive
medications, reduce the dose. Discontinue INLYTA if hypertension is
severe and persistent despite use of antihypertensive therapy and
dose reduction of INLYTA, and discontinuation should be considered
if there is evidence of hypertensive crisis.
Arterial and venous thrombotic events have been observed and can
be fatal. Use with caution in patients who are at increased risk or
who have a history of these events.
Hemorrhagic events, including fatal events, have been reported.
INLYTA has not been studied in patients with evidence of untreated
brain metastasis or recent active gastrointestinal bleeding and
should not be used in those patients. If any bleeding requires
medical intervention, temporarily interrupt the INLYTA dose.
Cardiac failure has been observed and can be fatal. Monitor for
signs or symptoms of cardiac failure throughout treatment with
INLYTA. Management of cardiac failure may require permanent
discontinuation of INLYTA.
Gastrointestinal perforation and fistula, including death, have
occurred. Use with caution in patients at risk for gastrointestinal
perforation or fistula. Monitor for symptoms of gastrointestinal
perforation or fistula periodically throughout treatment.
Hypothyroidism requiring thyroid hormone replacement has been
reported. Monitor thyroid function before initiation of, and
periodically throughout, treatment.
No formal studies of the effect of INLYTA on wound healing have
been conducted. Stop INLYTA at least 24 hours prior to scheduled
surgery.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS) has
been observed. If signs or symptoms occur, permanently discontinue
treatment.
Monitor for proteinuria before initiation of, and periodically
throughout, treatment. For moderate to severe proteinuria, reduce
the dose or temporarily interrupt treatment.
Liver enzyme elevation has been observed during treatment with
INLYTA. Monitor ALT, AST, and bilirubin before initiation of, and
periodically throughout, treatment.
For patients with moderate hepatic impairment, the starting dose
should be decreased. INLYTA has not been studied in patients with
severe hepatic impairment.
Women of childbearing potential should be advised of potential
hazard to the fetus and to avoid becoming pregnant while receiving
INLYTA.
Avoid strong CYP3A4/5 inhibitors. If unavoidable, reduce the
dose. Grapefruit or grapefruit juice may also increase INLYTA
plasma concentrations and should be avoided.
Avoid strong CYP3A4/5 inducers and, if possible, avoid moderate
CYP3A4/5 inducers.
The most common (≥20%) adverse events (AEs) occurring in
patients receiving INLYTA (all grades, vs sorafenib) were diarrhea
(55% vs 53%), hypertension (40% vs 29%), fatigue (39% vs 32%),
decreased appetite (34% vs 29%), nausea (32% vs 22%), dysphonia
(31% vs 14%), hand-foot syndrome (27% vs 51%), weight decreased
(25% vs 21%), vomiting (24% vs 17%), asthenia (21% vs 14%), and
constipation (20% vs 20%).
The most common (≥10%) grade 3/4 AEs occurring in patients
receiving INLYTA (vs sorafenib) were hypertension (16% vs 11%),
diarrhea (11% vs 7%), and fatigue (11% vs 5%).
The most common (≥20%) lab abnormalities occurring in patients
receiving INLYTA (all grades, vs sorafenib) included increased
creatinine (55% vs 41%), decreased bicarbonate (44% vs 43%),
hypocalcemia (39% vs 59%), decreased hemoglobin (35% vs 52%),
decreased lymphocytes (absolute) (33% vs 36%), increased ALP (30%
vs 34%), hyperglycemia (28% vs 23%), increased lipase (27% vs 46%),
increased amylase (25% vs 33%), increased ALT (22% vs 22%), and
increased AST (20% vs 25%).
For more information and full Prescribing Information, visit
www.pfizer.com.
About SUTENT® (sunitinib malate)
SUTENT is an oral multi-kinase inhibitor that works by blocking
multiple molecular targets implicated in the growth, proliferation
and spread of cancer. Two important SUTENT targets, vascular
endothelial growth factor receptor (VEGFR) and platelet-derived
growth factor receptor (PDGFR) are expressed by many types of solid
tumors and are thought to play a crucial role in angiogenesis, the
process by which tumors acquire blood vessels, oxygen and nutrients
needed for growth. SUTENT also inhibits other targets important to
tumor growth, including KIT, FLT3 and RET.
SUTENT is indicated for the treatment of advanced renal cell
carcinoma (RCC), gastrointestinal stromal tumor (GIST) after
disease progression on or intolerance to imatinib mesylate, and
progressive, well-differentiated pancreatic neuroendocrine tumors
(pNET) in patients with unresectable locally advanced or metastatic
disease.
SUTENT Important Safety Information
Boxed Warning/Hepatotoxicity: Hepatotoxicity has been
observed in clinical trials and post-marketing experience.
This hepatotoxicity may be severe, and deaths have been
reported. Monitor liver function tests before initiation of
treatment, during each cycle of treatment, and as clinically
indicated. SUTENT should be interrupted for Grade 3 or 4
drug-related hepatic adverse events and discontinued if there is no
resolution. Do not restart SUTENT if patients subsequently
experience severe changes in liver function tests or have other
signs and symptoms of liver failure.
Pregnancy: Women of childbearing potential should be
advised of the potential hazard to the fetus and to avoid becoming
pregnant.
Nursing mothers: Given the potential for serious adverse
reactions (ARs) in nursing infants, a decision should be made
whether to discontinue nursing or SUTENT.
Cardiovascular events: Cardiovascular events, including
heart failure, cardiomyopathy, myocardial ischemia, and myocardial
infarction, some of which were fatal, have been reported. Use
SUTENT with caution in patients who are at risk for, or who have a
history of, these events. Monitor patients for signs and symptoms
of congestive heart failure (CHF) and, in the presence of clinical
manifestations, discontinuation is recommended. Patients who
presented with cardiac events, pulmonary embolism, or
cerebrovascular events within the previous 12 months were excluded
from clinical studies.
QT interval prolongation and Torsades de Pointes: SUTENT
has been shown to prolong QT interval 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. Monitoring with on-treatment electrocardiograms and
electrolytes should be considered.
Hypertension: 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.
Reversible posterior leukoencephalopathy syndrome (RPLS):
There have been (<1%) reports, some fatal, of subjects
presenting with seizures and radiological evidence of RPLS.
Hemorrhagic events: Hemorrhagic events, including
tumor-related hemorrhage such as pulmonary hemorrhage, have
occurred. Some of these events were fatal. Perform serial complete
blood counts (CBCs) and physical examinations.
Tumor lysis syndrome (TLS): Cases of TLS have been
reported primarily in patients with high tumor burden. Monitor
these patients closely and treat as clinically indicated.
Thrombotic microangiopathy (TMA): 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: Proteinuria and nephrotic syndrome have been
reported. Some of these cases have resulted in renal failure and
fatal outcomes. Perform baseline and periodic urinalysis during
treatment, with follow-up measurement of 24-hour urine protein as
clinically indicated. Interrupt SUTENT and dose reduce if 24-hour
urine protein is ≥3 g; discontinue SUTENT in cases of nephrotic
syndrome or repeat episodes of urine protein ≥3 g despite dose
reductions.
Dermatologic toxicities: Severe cutaneous reactions have
been reported, including cases of 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, SUTENT treatment should be discontinued. 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: Thyroid dysfunction may occur.
Monitor thyroid function in patients with signs and/or symptoms of
thyroid dysfunction, including hypothyroidism, hyperthyroidism, and
thyroiditis, and treat per standard medical practice.
Hypoglycemia: SUTENT has been associated with symptomatic
hypoglycemia, which may result in 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 SUTENT. Assess whether anti-diabetic
drug dosage needs to be adjusted to minimize the risk of
hypoglycemia.
Osteonecrosis of the jaw (ONJ): ONJ has been reported.
Consider preventive dentistry prior to treatment with SUTENT. If
possible, avoid invasive dental procedures, particularly in
patients receiving bisphosphonates.
Wound healing: Cases of impaired wound healing have been
reported. Temporary interruption of therapy with SUTENT is
recommended in patients undergoing major surgical procedures.
Adrenal function: Adrenal hemorrhage was observed in
animal studies. Monitor adrenal function in case of stress such as
surgery, trauma, or severe infection.
Laboratory tests: CBCs with platelet count and serum
chemistries including phosphate should be performed at the
beginning of each treatment cycle for patients receiving treatment
with SUTENT.
CYP3A4 coadministration: 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 (advanced
RCC): The most common ARs occurring 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 (occurring 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
occurring 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 (occurring 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 occurring 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 commonly
reported grade 3/4 ARs (occurring 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%).
Most common grade 3/4 lab abnormalities (advanced pNET):
The most common grade 3/4 lab abnormalities (occurring in ≥5% of
patients with advanced pNET receiving SUTENT vs placebo) 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).
About XALKORI® (crizotinib)
XALKORI is indicated for the treatment of patients with
metastatic non-small cell lung cancer (NSCLC) whose tumors are
anaplastic lymphoma kinase (ALK)-positive as detected by an
FDA-approved test. XALKORI is also indicated for the treatment of
patients with metastatic NSCLC whose tumors are ROS1-positive.
XALKORI Important Safety Information
Hepatotoxicity: Drug-induced hepatotoxicity with fatal
outcome occurred in 0.1% of patients treated with XALKORI across
clinical trials (n=1719). Transaminase elevations generally
occurred within the first 2 months. Monitor with liver function
tests including ALT, AST, and total bilirubin every 2 weeks during
the first 2 months of treatment, then once a month and as
clinically indicated, with more frequent repeat testing for
increased liver transaminases, alkaline phosphatase, or total
bilirubin in patients who develop transaminase elevations.
Permanently discontinue for ALT/AST elevation >3 times ULN with
concurrent total bilirubin elevation >1.5 times ULN (in the
absence of cholestasis or hemolysis); otherwise, temporarily
suspend and dose-reduce XALKORI as indicated.
Interstitial Lung Disease (Pneumonitis): Severe,
life-threatening, or fatal interstitial lung disease
(ILD)/pneumonitis can occur. Across clinical trials (n=1719), 2.9%
of XALKORI-treated patients had any grade ILD, 1.0% had Grade 3/4,
and 0.5% had fatal ILD. ILD generally occurred within 3 months
after initiation of treatment. Monitor for pulmonary symptoms
indicative of ILD/pneumonitis. Exclude other potential causes and
permanently discontinue XALKORI in patients with drug-related
ILD/pneumonitis.
QT Interval Prolongation: QTc prolongation can occur.
Across clinical trials (n=1616), 2.1% of patients had QTcF
(corrected QT by the Fridericia method) ≥500 ms and 5.0% had an
increase from baseline QTcF ≥60 ms by automated machine-read
evaluation of ECGs. Avoid use in patients with congenital long QT
syndrome. Monitor with ECGs and electrolytes in patients with
congestive heart failure, bradyarrhythmias, electrolyte
abnormalities, or who are taking medications that prolong the QT
interval. Permanently discontinue XALKORI in patients who develop
QTc >500 ms or ≥60 ms change from baseline with Torsade de
pointes, polymorphic ventricular tachycardia, or signs/symptoms of
serious arrhythmia. Withhold XALKORI in patients who develop QTc
>500 ms on at least 2 separate ECGs until recovery to a QTc ≤480
ms, then resume at a reduced dose.
Bradycardia: Symptomatic bradycardia can occur. Across
clinical trials, bradycardia occurred in 12.7% of patients treated
with XALKORI (n=1719). Avoid use in combination with other agents
known to cause bradycardia. Monitor heart rate and blood pressure
regularly. In cases of symptomatic bradycardia that is not
life-threatening, hold XALKORI until recovery to asymptomatic
bradycardia or to a heart rate of ≥60 bpm, re-evaluate the use of
concomitant medications, and adjust the dose of XALKORI.
Permanently discontinue for life-threatening bradycardia due to
XALKORI; however, if associated with concomitant medications known
to cause bradycardia or hypotension, hold XALKORI until recovery to
asymptomatic bradycardia or to a heart rate of ≥60 bpm. If
concomitant medications can be adjusted or discontinued, restart
XALKORI at 250 mg once daily with frequent monitoring.
Severe Visual Loss: Across clinical trials, the incidence
of Grade 4 visual field defect with vision loss was 0.2% (n=1719).
Discontinue XALKORI in patients with new onset of severe visual
loss (best corrected vision less than 20/200 in one or both eyes).
Perform an ophthalmological evaluation. There is insufficient
information to characterize the risks of resumption of XALKORI in
patients with a severe visual loss; a decision to resume should
consider the potential benefits to the patient.
Vision Disorders: Most commonly visual impairment,
photopsia, blurred vision or vitreous floaters, occurred in 63.1%
of 1719 patients. The majority (95%) of these patients had Grade 1
visual adverse reactions. 0.8% of patients had Grade 3 and 0.2% had
Grade 4 visual impairment. The majority of patients on the XALKORI
arms in Studies 1 and 2 (>50%) reported visual disturbances
which occurred at a frequency of 4-7 days each week, lasted up to 1
minute, and had mild or no impact on daily activities.
Embryo-Fetal Toxicity: XALKORI can cause fetal harm when
administered to a pregnant woman. Advise of the potential risk to
the fetus. Advise females of reproductive potential and males with
female partners of reproductive potential to use effective
contraception during treatment and for at least 45 days (females)
or 90 days (males) respectively, following the final dose of
XALKORI.
ROS1-positive Metastatic NSCLC: Safety was evaluated in
50 patients with ROS1-positive metastatic NSCLC from a single-arm
study, and was generally consistent with the safety profile of
XALKORI evaluated in patients with ALK-positive metastatic NSCLC.
Vision disorders occurred in 92% of patients in the ROS1 study; 90%
of patients had Grade 1 vision disorders and 2% had Grade 2.
Adverse Reactions: Safety was evaluated in a phase 3
study in previously untreated patients with ALK-positive metastatic
NSCLC randomized to XALKORI (n=171) or chemotherapy (n=169).
Serious adverse events were reported in 34% of patients treated
with XALKORI, the most frequent were dyspnea (4.1%) and pulmonary
embolism (2.9%). Fatal adverse events in XALKORI-treated patients
occurred in 2.3% of patients, consisting of septic shock, acute
respiratory failure, and diabetic ketoacidosis. Common adverse
reactions (all grades) occurring in ≥25% and more commonly (≥5%) in
patients treated with XALKORI vs chemotherapy were vision disorder
(71% vs 10%), diarrhea (61% vs 13%), edema (49% vs 12%), vomiting
(46% vs 36%), constipation (43% vs 30%), upper respiratory
infection (32% vs 12%), dysgeusia (26% vs 5%), and abdominal pain
(26% vs 12%). Grade 3/4 reactions occurring at a ≥2% higher
incidence with XALKORI vs chemotherapy were QT prolongation (2% vs
0%), and constipation (2% vs 0%). In patients treated with XALKORI
vs chemotherapy, the following occurred: elevation of ALT (any
grade [79% vs 33%] or Grade 3/4 [15% vs 2%]); elevation of AST (any
grade [66% vs 28%] or Grade 3/4 [8% vs 1%]); neutropenia (any grade
[52% vs 59%] or Grade 3/4 [11% vs 16%]); lymphopenia (any grade
[48% vs 53%] or Grade 3/4 [7% vs 13%]); hypophosphatemia (any grade
[32% vs 21%] or Grade 3/4 [10% vs 6%]). In patients treated with
XALKORI vs chemotherapy, renal cysts occurred (5% vs 1%). Nausea
(56%), decreased appetite (30%), fatigue (29%), and neuropathy
(21%) also occurred in patients taking XALKORI.
Drug Interactions: Exercise caution with concomitant use
of moderate CYP3A inhibitors. Avoid grapefruit or grapefruit juice
which may increase plasma concentrations of crizotinib. Avoid
concomitant use of strong CYP3A inducers and inhibitors. Avoid
concomitant use of CYP3A substrates with narrow therapeutic range
in patients taking XALKORI. If concomitant use of CYP3A substrates
with narrow therapeutic range is required in patients taking
XALKORI, dose reductions of the CYP3A substrates may be required
due to adverse reactions.
Lactation: Because of the potential for adverse reactions
in breastfed infants, advise females not to breast feed during
treatment with XALKORI and for 45 days after the final dose.
Hepatic Impairment: XALKORI has not been studied in
patients with hepatic impairment. As crizotinib is extensively
metabolized in the liver, hepatic impairment is likely to increase
plasma crizotinib concentrations. Use caution in patients with
hepatic impairment.
Renal Impairment: Decreases in estimated glomerular
filtration rate occurred in patients treated with XALKORI.
Administer XALKORI at a starting dose of 250 mg taken orally once
daily in patients with severe renal impairment (CLcr <30 mL/min)
not requiring dialysis. No starting dose adjustment is needed for
patients with mild and moderate renal impairment.
For more information and full Prescribing Information, visit
www.XALKORI.com.
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 healthcare
products. Our global portfolio includes medicines and vaccines as
well as many of the world's best-known consumer healthcare
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, Pfizer has worked to make a difference for
all who rely on us. For more information, please visit us at
www.pfizer.com. In addition, to learn more, 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
as of September 28, 2016. 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 Pfizer’s
oncology portfolio, including avelumab (MSB0010718C), IBRANCE
(palbociclib), INLYTA (axitinib), SUTENT (sunitinib), XALKORI
(crizotinib), PF-06647020 and PF-04518600, 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 Pfizer’s oncology products; the
uncertainties inherent in research and development, including the
ability to meet anticipated clinical study commencement and
completion dates as well as the possibility of unfavorable study
results, including unfavorable new clinical data and additional
analyses of existing clinical data; risks associated with interim
data; the risk that clinical trial data are subject to differing
interpretations, and, even when we view data as sufficient to
support the safety and/or effectiveness of a product candidate,
regulatory authorities may not share our views and may require
additional data or may deny approval altogether; whether regulatory
authorities will be satisfied with the design of and results from
our clinical studies; whether and when drug applications may be
filed in any jurisdictions for any potential indications for
Pfizer’s oncology products and product candidates; whether and when
any such 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 Pfizer’s oncology
products and product candidates; 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, 2015 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.
i IBRANCE® (palbociclib) Prescribing Information. New York. NY:
Pfizer Inc: 2016.
ii Weinberg RA. pRb and Control of the Cell Cycle Clock. In:
Weinberg RA, ed. The Biology of Cancer. 2nd ed. New York, NY:
Garland Science; 2014:275-329.
iii Sotillo E, Grana X. Escape from Cellular Quiescence. In:
Enders GH, ed. Cell Cycle Deregulation in Cancer. New York, NY:
Humana Press; 2010:3-22.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20160928005435/en/
Pfizer Inc.Media:EuropeLisa O’Neill, +44.1737.331536orU.S.Sally
Beatty, 212-733-6566orInvestors:Ryan Crowe, 212-733-8160
Pfizer (NYSE:PFE)
Historical Stock Chart
From Aug 2024 to Sep 2024
Pfizer (NYSE:PFE)
Historical Stock Chart
From Sep 2023 to Sep 2024