THOUSAND OAKS, Calif.,
Oct. 5, 2016 /PRNewswire/ -- Amgen
(NASDAQ:AMGN) today announced that new data on IMLYGIC®
(talimogene laherparepvec) in combination with an immune checkpoint
inhibitor and results from retrospective analyses on
Vectibix® (panitumumab) will be presented at the
European Society for Medical Oncology (ESMO) 2016 Congress,
Oct. 7-11, 2016, in Copenhagen.
IMLYGIC presentations include interim results from a Phase 2
trial evaluating IMLYGIC in combination with ipilimumab versus
ipilimumab alone in patients with unresected stage IIIB-IV
melanoma. Vectibix abstracts include retrospective analyses of the
first-line Phase 3 PRIME and PEAK studies, evaluating the
association between tumor site of origin and treatment efficacy in
patients with RAS wild-type metastatic colorectal cancer
(mCRC).
"We look forward to sharing our research into the combination of
a checkpoint inhibitor and Amgen's oncolytic immunotherapy in
metastatic melanoma," said Sean E.
Harper, M.D., executive vice president of Research and
Development at Amgen. "Additionally, we are excited about our data
around tumor site of origin as one of a number of potential factors
that may inform treatment decisions for patients with metastatic
colorectal cancer."
IMLYGIC data:
- Interim safety and efficacy of a randomized (1:1),
open-label phase 2 study of talimogene laherparepvec (T) and
ipilimumab (I) vs I alone in unresected, stage IIIB-IV
melanoma
Abstract #1108PD, Poster Discussion, Monday, Oct. 10 from 11
a.m.-noon CET at Bella Center, Rome
Vectibix data:
- Outcome according to left vs. right side in the panitumumab
studies
Special Session, Monday, Oct. 10 from
11:35-11:50 a.m. CET at Bella Center,
Copenhagen
- Primary tumor sidedness impacts on prognosis and treatment
outcome: results from three randomized studies of panitumumab plus
chemotherapy versus chemotherapy or chemotherapy plus bevacizumab
in 1st and 2nd line RAS/BRAF WT mCRC
Abstract #89P, Poster, Monday, Oct.
10 from 1-2 p.m. CET at Bella
Center, Hall E
- Importance of tumour symptoms and extent of disease on
efficacy of first-line FOLFOX4 ± panitumumab (pmab) in patients
(pts) with RAS wild-type (WT)/BRAF WT metastatic
colorectal cancer (mCRC) in the PRIME study
Abstract #482P, Poster, Monday, Oct.
10 from 1-2 p.m. CET at Bella
Center, Hall E
- Impact of depth of response (DpR) on survival in patients
(pts) with RAS wild-type (WT) metastatic colorectal cancer
(mCRC) receiving first-line panitumumab + FOLFOX4 vs
FOLFOX4
Abstract #485P, Poster, Monday, Oct.
10 from 1-2 p.m. CET at Bella
Center, Hall E
- Efficacy of first-line modified FOLFOX6 with panitumumab or
bevacizumab in RAS wild-type/BRAF wild-type
metastatic colorectal cancer: Impact of tumour symptoms and extent
of disease
Abstract #501P, Poster, Monday, Oct.
10 from 1-2 p.m. CET at Bella
Center, Hall E
- Associations between dermatologic toxicity severity, patient
characteristics, and efficacy among patients treated with
panitumumab (Pmab) and chemotherapy
Abstract #531P, Poster, Monday, Oct.
10 from 1-2 p.m. CET at Bella
Center, Hall E
Abstracts are currently available on the ESMO website.
About IMLYGIC® (talimogene laherparepvec) in the
EU
IMLYGIC is an oncolytic immunotherapy that is
derived from HSV-1, which is commonly called the cold sore virus.
IMLYGIC has been modified to replicate within tumors and to produce
the immune stimulatory protein human GM-CSF. IMLYGIC causes the
death of tumor cells and the release of tumor-derived antigens. It
is thought that, together with GM-CSF, it will promote a systemic
anti-tumor immune response and an effector T cell response.
Important EU Product Safety Information
▼ This product is subject to additional monitoring. All
suspected adverse reactions should be reported in accordance with
the national reporting system.
The safety of IMLYGIC was evaluated in the pivotal study where
292 patients received at least one dose of IMLYGIC (see section
5.1). The median duration of exposure to IMLYGIC was 23 weeks (5.3
months). Twenty-six (26) patients were exposed to IMLYGIC for at
least one year.
The most commonly reported adverse reactions (≥ 25 percent) in
IMLYGIC-treated patients were fatigue (50.3 percent), chills (48.6
percent), pyrexia (42.8 percent), nausea (35.6 percent),
influenza-like illness (30.5 percent), and injection site pain
(27.7 percent). Overall, ninety-eight percent (98 percent) of these
adverse reactions reported were mild or moderate in severity. The
most common grade 3 or higher adverse reaction was cellulitis (2.1
percent) (see section 4.4).
Please refer to the Summary of Product Characteristics for
full European prescribing information.
About IMLYGIC® (talimogene laherparepvec) in
the U.S.
IMLYGIC is a genetically modified herpes simplex
type 1 virus that is injected directly into tumors. IMLYGIC
replicates inside tumor cells and produces GM-CSF, an
immunostimulatory protein. IMLYGIC then causes the cell to rupture
and die in a process called lysis. The rupture of the cancer cells
causes the release of tumor-derived antigens, which together with
virally derived GM-CSF may help to promote an anti-tumor immune
response. However, the exact mechanism of action is unknown.
IMLYGIC is the first oncolytic viral therapy approved by the
U.S. Food and Drug Administration (FDA) based on
therapeutic benefit demonstrated in a pivotal study. IMLYGIC is a
genetically modified oncolytic viral therapy indicated for the
local treatment of unresectable cutaneous, subcutaneous, and nodal
lesions in patients with melanoma recurrent after initial surgery.
IMLYGIC has not been shown to improve overall survival or have an
effect on visceral metastases.
Important U.S. Safety Information Contraindications
- Do not administer IMLYGIC® to immunocompromised
patients, including those with a history of primary or acquired
immunodeficient states, leukemia, lymphoma, AIDS or other clinical
manifestations of infection with human immunodeficiency viruses,
and those on immunosuppressive therapy, due to the risk of
life-threatening disseminated herpetic infection.
- Do not administer IMLYGIC® to pregnant
patients.
Warnings and Precautions
- Accidental exposure to IMLYGIC® may lead
to transmission of IMLYGIC® and herpetic infection,
including during preparation and administration. Health care
providers, close contacts, pregnant women, and newborns should
avoid direct contact with injected lesions, dressings, or body
fluids of treated patients. The affected area in exposed
individuals should be cleaned thoroughly with soap and water and/or
a disinfectant.
- Caregivers should wear protective gloves when assisting
patients in applying or changing occlusive dressings and observe
safety precautions for disposal of used dressings, gloves, and
cleaning materials. Exposed individuals should clean the affected
area thoroughly with soap and water and/or a disinfectant.
- To prevent possible inadvertent transfer of IMLYGIC®
to other areas of the body, patients should be advised to avoid
touching or scratching injection sites or occlusive dressings.
- Herpetic infections: Herpetic infections (including
cold sores and herpetic keratitis) have been reported in
IMLYGIC®-treated patients. Disseminated herpetic
infection may also occur in immunocompromised patients. Patients
who develop suspicious herpes-like lesions should follow standard
hygienic practices to prevent viral transmission.
- Patients or close contacts with suspected signs or symptoms of
a herpetic infection should contact their health care provider to
evaluate the lesions. Suspected herpetic lesions should be reported
to Amgen at 1-855-IMLYGIC (1-855-465-9442). Patients or
close contacts have the option of follow-up testing for further
characterization of the infection.
- IMLYGIC® is sensitive to acyclovir. Acyclovir or
other antiviral agents may interfere with the effectiveness of
IMLYGIC®. Consider the risks and benefits of
IMLYGIC® treatment before administering antiviral agents
to manage herpetic infection.
- Injection Site Complications: Necrosis or
ulceration of tumor tissue may occur during IMLYGIC®
treatment. Cellulitis and systemic bacterial infection have been
reported in clinical studies. Careful wound care and infection
precautions are recommended, particularly if tissue necrosis
results in open wounds.
- Impaired healing at the injection site has been reported.
IMLYGIC® may increase the risk of impaired healing in
patients with underlying risk factors (e.g., previous radiation at
the injection site or lesions in poorly vascularized areas). If
there is persistent infection or delayed healing of the injection
site, consider the risks and benefits of continuing treatment.
- Immune-Mediated events including
glomerulonephritis, vasculitis, pneumonitis, worsening psoriasis,
and vitiligo have been reported in patients treated with
IMLYGIC®. Consider the risks and benefits of
IMLYGIC® before initiating treatment in patients who
have underlying autoimmune disease or before continuing treatment
in patients who develop immune-mediated events.
- Plasmacytoma at Injection Site: Plasmacytoma in
proximity to the injection site has been reported in a patient with
smoldering multiple myeloma after IMLYGIC®
administration in a clinical study. Consider the risks and benefits
of IMLYGIC® in patients with multiple myeloma or in whom
plasmacytoma develops during treatment.
Adverse Reactions
- The most commonly reported adverse drug reactions (>25%) in
IMLYGIC®-treated patients were fatigue, chills, pyrexia,
nausea, influenza-like illness, and injection site pain. Pyrexia,
chills, and influenza-like illness can occur at any time during
IMLYGIC® treatment, but were more frequent during the
first 3 months of treatment.
- The most common Grade 3 or higher adverse reaction was
cellulitis.
Please see full U.S. Prescribing Information and Medication
Guide for IMLYGIC® at www.IMLYGIC.com.
About Vectibix® (panitumumab) in Europe
Vectibix is a fully human
anti-epidermal growth factor receptor (EGFR) antibody approved by
the European Medicines Agency (EMA) for the treatment of
mCRC.1 The safety and efficacy of Vectibix have not been
studied in patients with renal or hepatic impairment.1
Vectibix was approved in Europe in
December 2007 as a monotherapy for
the treatment of patients with EGFR-expressing mCRC with
non-mutated (wild-type) KRAS genes after failure of standard
chemotherapy regimens.2
In April 2015, the European
Commission (EC) approved a new use of Vectibix as first-line
treatment in combination with FOLFIRI for the treatment of adult
patients with RAS wild-type mCRC.3 In
November 2011, the EC expanded the
marketing authorization to include indications for the treatment of
patients with KRAS wild-type mCRC in first-line in
combination with FOLFOX and in second-line in combination with
FOLFIRI in patients who have received first-line
fluoropyrimidine-based chemotherapy (excluding
irinotecan).4
Globally, over 240,000 patients have been treated with Vectibix
and more than 6,000 patients have participated in Amgen-sponsored
panitumumab clinical trials.5
EU Product Safety Information
Summary of safety profile
Based on an analysis of all mCRC clinical trial patients receiving
Vectibix monotherapy and in combination with chemotherapy (n =
2,588), the most commonly reported adverse reactions are skin
reactions occurring in 93% of patients. These reactions are related
to the pharmacologic effects of Vectibix, and the majority are mild
to moderate in nature with 25% severe (grade 3 NCI-CTC) and < 1%
life threatening (grade 4 NCI-CTC). For clinical management of skin
reactions, including dose modification recommendations, see section
4.4. Very commonly reported adverse reactions occurring in ≥ 20% of
patients were gastrointestinal disorders [diarrhoea (50%), nausea
(41%), vomiting (27%), constipation (23%) and abdominal pain
(23%)]; general disorders [fatigue (37%), pyrexia (20%)];
metabolism and nutrition disorders [anorexia (27%)]; infections and
infestations [paronychia (20%)]; and skin and subcutaneous
disorders [rash (45%), dermatitis acneiform (39%), pruritus (35%),
erythema (30%) and dry skin (22%)].
Special warnings and precautions for use
Dermatologic
reactions and soft tissue toxicity
Dermatologic related reactions, a pharmacologic effect observed
with epidermal growth factor receptor (EGFR) inhibitors, are
experienced with nearly all patients (approximately 90%) treated
with Vectibix. Severe (NCI-CTC grade 3) skin reactions were
reported in 34% and life-threatening (NCICTC grade 4) skin
reactions in < 1% of patients who received Vectibix in
combination with chemotherapy (n = 1,536) (see section 4.8). If a
patient develops dermatologic reactions that are grade 3 (CTCAE v
4.0) or higher, or that are considered intolerable, the following
dose modification is recommended:
Occurrence of
skin symptom(s):
≥ grade 31
|
Administration
of Vectibix
|
Outcome
|
Dose
regulation
|
Initial
occurrence
|
Withhold 1 or 2
doses
|
Improved (< grade
3)
|
Continuing infusion
at 100% of original dose
|
Not
recovered
|
Discontinue
|
At the second
occurrence
|
Withhold 1 or 2
doses
|
Improved (< grade
3)
|
Continuing infusion
at 80% of original dose
|
Not
recovered
|
Discontinue
|
At the third
occurrence
|
Withhold 1 or 2
doses
|
Improved (< grade
3)
|
Continuing infusion
at 60% of original dose
|
Not
recovered
|
Discontinue
|
At the fourth
occurrence
|
Discontinue
|
-
|
-
|
1Greater
than or equal to grade 3 is defined as severe or
life-threatening
|
In clinical studies, subsequent to the development of severe
dermatologic reactions (including stomatitis), infectious
complications including sepsis and necrotising fasciitis, in rare
cases leading to death, and local abscesses requiring incisions and
drainage were reported. Patients who have severe dermatologic
reactions or soft tissue toxicity or who develop worsening
reactions whilst receiving Vectibix should be monitored for the
development of inflammatory or infectious sequelae (including
cellulitis and necrotising fasciitis), and appropriate treatment
promptly initiated. Life threatening and fatal infectious
complications including necrotising fasciitis and sepsis have been
observed in patients treated with Vectibix. Rare cases of
Stevens-Johnson syndrome and toxic epidermal necrolysis have been
reported in patients treated with Vectibix in the post-marketing
setting. Withhold or discontinue Vectibix in the event of
dermatologic or soft tissue toxicity associated with severe or life
threatening inflammatory or infectious complications.
Treatment of dermatologic reactions should be based on severity
and may include a moisturiser, sun screen (SPF > 15 UVA and
UVB), and topical steroid cream (not stronger than 1%
hydrocortisone) applied to affected areas, and/or oral antibiotics.
It is also recommended that patients experiencing
rash/dermatological toxicities wear sunscreen and hats and limit
sun exposure as sunlight can exacerbate any skin reactions that may
occur.
Proactive skin treatment including skin moisturiser, sun screen
(SPF > 15 UVA and UVB), topical steroid cream (not stronger than
1% hydrocortisone) and an oral antibiotic (e.g. doxycycline) may be
useful in the management of dermatologic reactions. Patients may be
advised to apply moisturiser and sunscreen to face, hands, feet,
neck, back and chest every morning during treatment, and to apply
the topical steroid to face, hands, feet, neck, back and chest
every night during treatment.
Pulmonary complications
Patients with a history of, or evidence of, interstitial
pneumonitis or pulmonary fibrosis were excluded from clinical
studies. Cases of interstitial lung disease (ILD), both fatal and
non-fatal, have been reported, mainly from the Japanese population.
In the event of acute onset or worsening pulmonary symptoms,
Vectibix treatment should be interrupted and a prompt investigation
of these symptoms should occur. If ILD is diagnosed, Vectibix
should be permanently discontinued and the patient should be
treated appropriately. In patients with a history of interstitial
pneumonitis or pulmonary fibrosis, the benefits of therapy with
panitumumab versus the risk of pulmonary complications must be
carefully considered.
Electrolyte disturbances
Progressively decreasing serum magnesium levels leading to severe
(grade 4) hypomagnesaemia have been observed in some patients.
Patients should be periodically monitored for hypomagnesaemia and
accompanying hypocalcaemia prior to initiating Vectibix treatment,
and periodically thereafter for up 5 to 8 weeks after the
completion of treatment. Magnesium repletion is recommended, as
appropriate.
Other electrolyte disturbances, including hypokalaemia, have
also been observed. Monitoring as above and repletion as
appropriate of these electrolytes is also recommended.
Infusion related reactions
Across monotherapy and combination mCRC clinical studies (n =
2,588), infusion-related reactions (occurring within 24 hours of an
infusion) were reported in approximately 4% of Vectibix-treated
patients, of which < 1% were severe (NCI-CTC grade 3 and grade
4).
In the post-marketing setting, serious infusion-related
reactions have been reported, including rare post-marketing reports
with a fatal outcome. If a severe or life-threatening reaction
occurs during an infusion or at any time post-infusion [e.g.
presence of bronchospasm, angioedema, hypotension, need for
parenteral treatment, or anaphylaxis], Vectibix should be
permanently discontinued.
In patients experiencing a mild or moderate (CTCAE v 4.0 grades
1 and 2) infusion-related reaction the infusion rate should be
reduced for the duration of that infusion. It is recommended to
maintain this lower infusion rate in all subsequent infusions.
Hypersensitivity reactions occurring more than 24 hours after
infusion have been reported including a fatal case of angioedema
that occurred more than 24 hours after the infusion. Patients
should be informed of the possibility of a late onset reaction and
instructed to contact their physician if symptoms of a
hypersensitivity reaction occur.
Acute renal failure
Acute renal failure has been observed in patients who develop
severe diarrhoea and dehydration. Patients who experience severe
diarrhoea should be instructed to consult a healthcare professional
urgently.
Vectibix in combination with irinotecan, bolus 5-fluorouracil,
and leucovorin (IFL) chemotherapy
Patients receiving Vectibix in combination with the IFL regimen
[bolus 5-fluorouracil (500 mg/m2), leucovorin (20 mg/m2) and
irinotecan (125 mg/m2)] experienced a high incidence of severe
diarrhoea. Therefore administration of Vectibix in combination with
IFL should be avoided.
Vectibix in combination with bevacizumab and chemotherapy
regimens
A randomised, open-label, multicentre study of 1,053 patients
evaluated the efficacy of bevacizumab and oxaliplatin- or
irinotecan-containing chemotherapeutic regimens with and without
Vectibix in the first-line treatment of metastatic colorectal
cancer. Shortened progression free survival time and increased
deaths were observed in the patients receiving Vectibix in
combination with bevacizumab and chemotherapy. A greater frequency
of pulmonary embolism, infections (predominantly of dermatologic
origin), diarrhoea, electrolyte imbalances, nausea, vomiting and
dehydration was also observed in the treatment arms using Vectibix
in combination with bevacizumab and chemotherapy. An additional
analysis of efficacy data by KRAS status did not identify a
subset of patients who benefited from Vectibix in combination with
oxaliplatin- or irinotecan-based chemotherapy and bevacizumab. A
trend towards worse survival was observed with Vectibix in the
wild-type KRAS subset of the bevacizumab and oxaliplatin
cohort, and a trend towards worse survival was observed with
Vectibix in the bevacizumab and irinotecan cohort regardless of
KRAS mutational status. Therefore, Vectibix should not be
administered in combination with bevacizumab containing
chemotherapy.
Vectibix in combination with oxaliplatin-based chemotherapy in
patients with mutant RAS mCRC or for whom RAS tumour
status is unknown
The combination of Vectibix with oxaliplatin-containing
chemotherapy is contraindicated for patients with mutant RAS
mCRC or for whom RAS mCRC status is unknown.
In the primary analysis of a study (n = 1,183, 656 patients with
wild-type KRAS (exon 2) and 440 patients with mutant KRAS
tumours) evaluating panitumumab in combination with infusional
5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) compared to
FOLFOX alone as first-line therapy for mCRC, a shortened
progression-free survival (PFS) and overall survival (OS) time were
observed in patients with mutant KRAS tumours who received
panitumumab and FOLFOX (n = 221) vs. FOLFOX alone (n = 219).
A predefined retrospective subset analysis of 641 patients of
the 656 patients with wild-type KRAS (exon 2) tumours from
this study identified additional RAS (KRAS [exons 3
and 4] or NRAS [exons 2, 3, 4]) mutations in 16% (n = 108)
of patients. A shortening of PFS and OS was observed in patients
with mutant RAS tumours who received panitumumab and FOLFOX
(n = 51) versus FOLFOX alone (n = 57).
RAS mutational status should be determined using a
validated test method by an experienced laboratory (see section
4.2). If Vectibix is to be used in combination with FOLFOX then it
is recommended that mutational status be determined by a laboratory
that participates in a RAS External Quality Assurance
programme or wild-type status be confirmed in a duplicate test.
Ocular toxicities
Serious cases of keratitis and ulcerative keratitis have been
rarely reported in the post-marketing setting. Patients presenting
with signs and symptoms suggestive of keratitis such as acute or
worsening: eye inflammation, lacrimation, light sensitivity,
blurred vision, eye pain and/or red eye should be referred promptly
to an ophthalmology specialist.
If a diagnosis of ulcerative keratitis is confirmed, treatment
with Vectibix should be interrupted or discontinued. If keratitis
is diagnosed, the benefits and risks of continuing treatment should
be carefully considered.
Vectibix should be used with caution in patients with a history
of keratitis, ulcerative keratitis or severe dry eye. Contact lens
use is also a risk factor for keratitis and ulceration.
Patients with ECOG 2 performance status treated with Vectibix in
combination with chemotherapy
For patients with ECOG 2 performance status, assessment of
benefit-risk is recommended prior to initiation of Vectibix in
combination with chemotherapy for treatment of mCRC. A positive
benefitrisk balance has not been documented in patients with ECOG 2
performance status.
Elderly patients
No overall differences in safety or efficacy were observed in
elderly patients (≥ 65 years of age) treated with Vectibix
monotherapy. However, an increased number of serious adverse events
were reported in elderly patients treated with Vectibix in
combination with FOLFIRI or FOLFOX chemotherapy compared to
chemotherapy alone.
Other precautions
This medicinal product contains 0.150 mmol sodium (which is 3.45 mg
sodium) per ml of concentrate. To be taken into consideration by
patients on a controlled sodium diet.
To see the full prescribing information, visit
http://www.vectibix.eu/.
About Vectibix® (panitumumab) in the
U.S.
Vectibix is the first fully human monoclonal
anti-epidermal growth factor receptor (EGFR) antibody approved by
the FDA for the treatment of mCRC. Vectibix was approved in the
U.S. in September 2006 as a monotherapy for the treatment of
patients with EGFR-expressing mCRC after disease progression after
prior treatment with fluoropyrimidine-, oxaliplatin-, and
irinotecan-containing chemotherapy.
In May 2014, the FDA approved Vectibix for use in combination
with FOLFOX, as first-line treatment in patients with wild-type
KRAS (exon 2) mCRC. With this approval, Vectibix became the
first-and-only biologic therapy indicated for use with FOLFOX, one
of the most commonly used chemotherapy regimens, in the first-line
treatment of mCRC for patients with wild-type KRAS mCRC.
Important U.S. Product
Information
Vectibix® is indicated
for the treatment of patients with
wild-type KRAS (exon 2 in codons 12 or 13)
metastatic colorectal cancer (mCRC) as determined by
an FDA-approved test for this use:
- As first-line therapy in combination with FOLFOX
- As monotherapy following disease progression after prior
treatment with fluoropyrimidine-, oxaliplatin-, and
irinotecan-containing chemotherapy
Limitation of Use: Vectibix® is not indicated
for the treatment of patients with RAS-mutant mCRC or
for whom RAS mutation status is unknown.
WARNING: DERMATOLOGIC TOXICITY
Dermatologic
Toxicity: Dermatologic toxicities occurred in 90% of patients and
were severe (NCI-CTC grade 3 or higher) in 15% of patients
receiving Vectibix monotherapy.
In Study 1, dermatologic toxicities occurred in 90% of patients
and were severe (NCI-CTC grade 3 and higher) in 15% of patients
with mCRC receiving Vectibix®. The clinical
manifestations included, but were not limited to, acneiform
dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia,
dry skin and skin fissures.
Monitor patients who develop dermatologic or soft tissue
toxicities while receiving Vectibix® for the
development of inflammatory or infectious sequelae.
Life-threatening and fatal infectious complications including
necrotizing fasciitis, abscesses and sepsis have been observed in
patients treated with Vectibix®. Life-threatening
and fatal bullous mucocutaneous disease with blisters, erosions and
skin sloughing has also been observed in patients treated with
Vectibix®. It could not be determined whether
these mucocutaneous adverse reactions were directly related to EGFR
inhibition or to idiosyncratic immune-related effects (e.g.,
Stevens-Johnson syndrome or toxic epidermal necrolysis). Withhold
or discontinue Vectibix® for dermatologic or
soft tissue toxicity associated with severe or life-threatening
inflammatory or infectious complications. Dose modifications for
Vectibix® concerning dermatologic toxicity are
provided in the product labeling. Vectibix® is
not indicated for the treatment of patients with colorectal cancer
that harbor somatic mutations in exon 2 (codons 12 and 13), exon 3
(codons 59 and 61), and exon 4 (codons 117 and 146) of either
KRAS or NRAS and hereafter is referred
to as "RAS."
Retrospective subset analyses across several randomized clinical
trials were conducted to investigate the role
of RAS mutations on the clinical effects of
anti-EGFR-directed monoclonal antibodies (panitumumab or
cetuximab). Anti-EGFR antibodies in patients with tumors
containing RAS mutations resulted in exposing
those patients to anti-EGFR related adverse reactions without
clinical benefit from these agents.
Additionally, in Study 3, 272 patients
with RAS-mutant mCRC tumors received
Vectibix® in combination with FOLFOX and 276
patients received FOLFOX alone. In an exploratory subgroup
analysis, OS was shorter (HR = 1.21, 95% CI 1.01-1.45) in patients
with RAS-mutant mCRC who received
Vectibix® and FOLFOX versus FOLFOX
alone.
Progressively decreasing serum magnesium levels leading to
severe (Grade 3-4) hypomagnesemia occurred in up to 7% (in Study 2)
of patients across clinical trials. Monitor patients for
hypomagnesemia and hypocalcemia prior to initiating
Vectibix® treatment, periodically during
Vectibix® treatment, and for up to 8 weeks after
the completion of treatment. Other electrolyte disturbances,
including hypokalemia, have also been observed. Replete magnesium
and other electrolytes as appropriate.
In Study 1, 4% of patients experienced infusion reactions and 1%
of patients experienced severe infusion reactions (CTCAE v 3.0
grade 3-4). Infusion reactions, manifesting as fever, chills,
dyspnea, bronchospasm, and hypotension, can occur following
Vectibix® administration. Fatal infusion
reactions occurred in postmarketing experience. Terminate the
infusion for severe infusion reactions.
Severe diarrhea and dehydration, leading to acute renal failure
and other complications, have been observed in patients treated
with Vectibix® in combination with
chemotherapy.
Fatal and non-fatal cases of interstitial lung disease (ILD)
(1%) and pulmonary fibrosis have been observed in patients treated
with Vectibix®. Pulmonary fibrosis occurred in
less than 1% (2/1467) of patients enrolled in clinical studies of
Vectibix®. In the event of acute onset or
worsening of pulmonary symptoms, interrupt
Vectibix® therapy. Discontinue
Vectibix® therapy if ILD is confirmed.
In patients with a history of interstitial pneumonitis or
pulmonary fibrosis, or evidence of interstitial pneumonitis or
pulmonary fibrosis, the benefits of therapy with
Vectibix® versus the risk of pulmonary
complications must be carefully considered.
Exposure to sunlight can exacerbate dermatologic toxicity.
Advise patients to wear sunscreen and hats and limit sun exposure
while receiving Vectibix®.
Keratitis and ulcerative keratitis, known risk factors for
corneal perforation, have been reported with
Vectibix® use. Monitor for evidence of
keratitis or ulcerative keratitis. Interrupt or discontinue
Vectibix® for acute or worsening
keratitis.
In an interim analysis of an open-label, multicenter, randomized
clinical trial in the first-line setting in patients with mCRC, the
addition of Vectibix® to the combination of
bevacizumab and chemotherapy resulted in decreased OS and increased
incidence of NCI-CTC grade 3–5 (87% vs 72%) adverse reactions.
NCI-CTC grade 3–4 adverse reactions occurring at a higher rate in
Vectibix®-treated patients included
rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%),
dehydration (16% vs 5%; primarily occurring in patients with
diarrhea), hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs
< 1%), and hypomagnesemia (4% vs 0).
NCI-CTC grade 3–5 pulmonary embolism occurred at a higher rate
in Vectibix®-treated patients (7% vs 3%) and
included fatal events in three (< 1%)
Vectibix®-treated patients.
As a result of the toxicities experienced, patients randomized
to Vectibix®, bevacizumab and chemotherapy
received a lower mean relative dose intensity of each
chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or
infusional 5-FU) over the first 24 weeks on study, compared with
those randomized to bevacizumab and chemotherapy.
Advise patients of the need for adequate contraception in both
males and females while receiving
Vectibix® and for 6 months after the last
dose of Vectibix® therapy.
Vectibix® may be transmitted from the mother
to the developing fetus, and has the potential to cause fetal harm
when administered to pregnant women.
Because many drugs are excreted into human milk and because of
the potential for serious adverse reactions in nursing infants from
Vectibix®, a decision should be made whether to
discontinue nursing or to discontinue the drug, taking into account
the importance of the drug to the mother. If nursing is
interrupted, it should not be resumed earlier than 2 months
following the last dose of Vectibix®.
Women who become pregnant during
Vectibix® treatment are encouraged to enroll
in Amgen's Pregnancy Surveillance Program. Women who are
nursing during Vectibix® treatment are
encouraged to enroll in Amgen's Lactation Surveillance
Program. Patients or their physicians should call
1-800-77-AMGEN (1-800-772-6436) to enroll.
In Study 1, the most common adverse reactions (> 20%)
with Vectibix® were skin rash with variable
presentations, paronychia, fatigue, nausea, and diarrhea. The most
common (> 5%) serious adverse reactions in the
Vectibix® arm were general physical health
deterioration and intestinal obstruction.
In Study 3, the most commonly reported adverse reactions (>
20%) in patients with wild-type KRAS mCRC
receiving Vectibix® (6 mg/kg every 2 weeks)
and FOLFOX therapy (N = 322) were diarrhea, stomatitis, mucosal
inflammation, asthenia, paronychia, anorexia, hypomagnesemia,
hypokalemia, rash, acneiform dermatitis, pruritus and dry skin.
Serious adverse reactions (> 2% difference between treatment
arms) in Vectibix®-treated patients with
wild-type KRAS mCRC were diarrhea and
dehydration.
To see the Vectibix® Prescribing Information,
including Boxed Warning visit www.vectibix.com.
About Amgen
Amgen is committed to unlocking the
potential of biology for patients suffering from serious illnesses
by discovering, developing, manufacturing and delivering innovative
human therapeutics. This approach begins by using tools like
advanced human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages
its expertise to strive for solutions that improve health outcomes
and dramatically improve people's lives. A biotechnology pioneer
since 1980, Amgen has grown to be one of the world's leading
independent biotechnology companies, has reached millions of
patients around the world and is developing a pipeline of medicines
with breakaway potential.
For more information, visit www.amgen.com and follow us on
www.twitter.com/amgen.
About Amgen's Commitment to Oncology
Amgen Oncology is
committed to helping patients take on some of the toughest cancers,
such as those that have been resistant to drugs, those that
progress rapidly through the body and those where limited treatment
options exist. Amgen's supportive care treatments help patients
combat certain side effects of strong chemotherapy, and our
targeted medicines and immunotherapies focus on more than a dozen
different malignancies, ranging from blood cancers to solid tumors.
With decades of experience providing therapies for cancer patients,
Amgen continues to grow its portfolio of innovative and biosimilar
oncology medicines.
Forward-Looking Statements
This news release contains
forward-looking statements that are based on the current
expectations and beliefs of Amgen. All statements, other than
statements of historical fact, are statements that could be deemed
forward-looking statements, including estimates of revenues,
operating margins, capital expenditures, cash, other financial
metrics, expected legal, arbitration, political, regulatory or
clinical results or practices, customer and prescriber patterns or
practices, reimbursement activities and outcomes and other such
estimates and results. Forward-looking statements involve
significant risks and uncertainties, including those discussed
below and more fully described in the Securities and Exchange
Commission reports filed by Amgen, including our most recent annual
report on Form 10-K and any subsequent periodic reports on Form
10-Q and Form 8-K. Unless otherwise noted, Amgen is providing this
information as of the date of this news release and does not
undertake any obligation to update any forward-looking statements
contained in this document as a result of new information, future
events or otherwise.
No forward-looking statement can be guaranteed and actual
results may differ materially from those we project.
Discovery or identification of new product candidates or
development of new indications for existing products cannot be
guaranteed and movement from concept to product is uncertain;
consequently, there can be no guarantee that any particular product
candidate or development of a new indication for an existing
product will be successful and become a commercial product.
Further, preclinical results do not guarantee safe and effective
performance of product candidates in humans. The complexity of the
human body cannot be perfectly, or sometimes, even adequately
modeled by computer or cell culture systems or animal models. The
length of time that it takes for us to complete clinical trials and
obtain regulatory approval for product marketing has in the past
varied and we expect similar variability in the future. Even when
clinical trials are successful, regulatory authorities may question
the sufficiency for approval of the trial endpoints we have
selected. We develop product candidates internally and through
licensing collaborations, partnerships and joint ventures. Product
candidates that are derived from relationships may be subject to
disputes between the parties or may prove to be not as effective or
as safe as we may have believed at the time of entering into such
relationship. Also, we or others could identify safety, side
effects or manufacturing problems with our products after they are
on the market.
Our results may be affected by our ability to successfully
market both new and existing products domestically and
internationally, clinical and regulatory developments involving
current and future products, sales growth of recently launched
products, competition from other products including biosimilars,
difficulties or delays in manufacturing our products and global
economic conditions. In addition, sales of our products are
affected by pricing pressure, political and public scrutiny and
reimbursement policies imposed by third-party payers, including
governments, private insurance plans and managed care providers and
may be affected by regulatory, clinical and guideline developments
and domestic and international trends toward managed care and
healthcare cost containment. Furthermore, our research, testing,
pricing, marketing and other operations are subject to extensive
regulation by domestic and foreign government regulatory
authorities. We or others could identify safety, side effects or
manufacturing problems with our products after they are on the
market. Our business may be impacted by government investigations,
litigation and product liability claims. In addition, our business
may be impacted by the adoption of new tax legislation or exposure
to additional tax liabilities. If we fail to meet the compliance
obligations in the corporate integrity agreement between us and the
U.S. government, we could become subject to significant sanctions.
Further, while we routinely obtain patents for our products and
technology, the protection offered by our patents and patent
applications may be challenged, invalidated or circumvented by our
competitors, or we may fail to prevail in present and future
intellectual property litigation. We perform a substantial amount
of our commercial manufacturing activities at a few key facilities
and also depend on third parties for a portion of our manufacturing
activities, and limits on supply may constrain sales of certain of
our current products and product candidate development. In
addition, we compete with other companies with respect to many of
our marketed products as well as for the discovery and development
of new products. Further, some raw materials, medical devices and
component parts for our products are supplied by sole third-party
suppliers. The discovery of significant problems with a product
similar to one of our products that implicate an entire class of
products could have a material adverse effect on sales of the
affected products and on our business and results of operations.
Our efforts to acquire other companies or products and to integrate
the operations of companies we have acquired may not be successful.
We may not be able to access the capital and credit markets on
terms that are favorable to us, or at all. We are increasingly
dependent on information technology systems, infrastructure and
data security. Our stock price is volatile and may be affected by a
number of events. Our business performance could affect or limit
the ability of our Board of Directors to declare a dividend or our
ability to pay a dividend or repurchase our common stock.
The scientific information discussed in this news release
related to our product candidates is preliminary and investigative.
Such product candidates are not approved by the U.S. Food and Drug
Administration, and no conclusions can or should be drawn regarding
the safety or effectiveness of the product candidates. Further, the
scientific information discussed in this news release relating to
new indications for our products is preliminary and investigative
and is not part of the labeling approved by the U.S. Food and Drug
Administration for the products. The products are not approved for
the investigational use(s) discussed in this news release, and no
conclusions can or should be drawn regarding the safety or
effectiveness of the products for these uses.
CONTACT: Amgen, Thousand
Oaks
Kristen Davis, 805-447-3008
(Media)
Trish Hawkins, 805-447-5631
(Media)
Arvind Sood, 805-447-1060
(Investors)
Amgen, Europe
Emma Gilbert, +41 41 79 179 9938
(Media)
References
- Vectibix® (panitumumab) EU Summary of Product
Characteristics.
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000741/WC500047710.pdf.
Accessed June 9, 2016.
- Amgen. Vectibix® Approved in the European Union for
the Treatment of Metastatic Colorectal Cancer.
http://investors.amgen.com/phoenix.zhtml?c=61656&p=irol-newsArticle&ID=1084566.
Accessed August 15, 2016.
- Amgen. European Commission Approves Amgen's
Vectibix® (panitumumab) As First-Line Treatment In
Combination With FOLFIRI Chemotherapy For Metastatic Colorectal
Cancer.
http://www.prnewswire.com/news-releases/european-commission-approves-amgens-vectibix-panitumumab-as-first-line-treatment-in-combination-with-folfiri-chemotherapy-for-metastatic-colorectal-cancer-300061112.html.
Accessed August 15, 2016.
- Amgen. Vectibix® (Panitumumab) Granted Approval for
Expanded Indications in the European Union.
http://www.prnewswire.com/news-releases/vectibix-panitumumab-granted-approval-for-expanded-indications-in-the-european-union-133871488.html.
Accessed August 15, 2016.
- Amgen data on file.
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SOURCE Amgen