Opdivo, the first and only anti-PD-1 immune
checkpoint inhibitor approved for adjuvant treatment of melanoma,
is indicated for both BRAF mutant and wild type patients
In the Phase 3 CheckMate -238 clinical
trial, Opdivo 3 mg/kg demonstrated unprecedented
recurrence-free survival versus Yervoy (ipilimumab) 10 mg/kg and
was well tolerated1,2
Bristol-Myers Squibb Company (NYSE:BMY) announced today that the
U.S. Food and Drug Administration (FDA) has approved Opdivo
(nivolumab) injection for intravenous use for the adjuvant
treatment of patients with melanoma with involvement of lymph nodes
or metastatic disease who have undergone complete resection.1 The
purpose of adjuvant therapy is to reduce the risk of recurrence
following surgical removal of the tumor and lymph nodes that
contain cancer. In the Phase 3 CheckMate -238 trial, Opdivo
significantly improved recurrence-free survival (RFS) versus an
active comparator, Yervoy (ipilimumab), in patients with stage
IIIB/C or stage IV melanoma after surgery.1,2 This benefit was
observed across important subgroups, including in both BRAF mutant
and BRAF wild-type patients.1 Opdivo is the first and only agent
approved for the adjuvant treatment of melanoma based on a
head-to-head trial against an active comparator with a proven
overall survival benefit.1-3
“Today’s approval builds on our leadership in melanoma, offering
physicians a new option with the potential to change the course of
the disease through earlier intervention. Opdivo is the first PD-1
inhibitor approved as an adjuvant treatment for any cancer,” said
Johanna Mercier, head, U.S. Commercial, Bristol-Myers Squibb. “Our
decision to study Opdivo versus Yervoy – an established standard of
care with a proven survival benefit – represents our relentless
pursuit to bring more effective treatments to patients.”
In the CheckMate -238 clinical trial, Opdivo demonstrated an
18-month RFS rate of 66.4% [95% confidence interval (CI): 61.8 to
70.6] compared with 52.7% for Yervoy (95% CI: 47.8 to 57.4), with
the median RFS not yet reached in either group. Opdivo reduced the
risk of disease recurrence by 35% versus Yervoy [hazard ratio (HR):
0.65; 95% CI: 0.53 to 0.80; p <0.0001].1,2
Opdivo is associated with the following Warnings and
Precautions: immune-mediated pneumonitis, colitis, hepatitis,
endocrinopathies, nephritis and renal dysfunction, skin adverse
reactions, encephalitis, other adverse reactions; infusion
reactions; and embryo-fetal toxicity. Please see the Important
Safety Information section below, including Boxed WARNING for
Yervoy regarding immune-mediated adverse reactions, as well as
additional information on the CA 184-029 trial.1,3
Opdivo received Breakthrough Therapy Designation from the FDA
for the adjuvant treatment of patients with high-risk, fully
resected melanoma in September 2017. Approximately three in every
10 patients with stage III melanoma currently receive adjuvant
therapy after surgery.4 Even with available treatment options, the
majority of stage IIIB and IIIC melanoma patients (71% and 85%,
respectively) experience disease recurrence within five years.5
Opdivo is the first programmed death-1 (PD-1) immune checkpoint
inhibitor to demonstrate superiority, including better
tolerability, versus Yervoy, a standard of care in this patient
population. Based on data from the CheckMate -238 trial, the
National Comprehensive Cancer Network® (NCCN®) recently added
nivolumab to its treatment guidelines for completely resected stage
IIIB/C melanoma and completely resected stage III melanoma with
clinical satellite or in-transit metastases.6
In CheckMate -238, adverse events (AEs) leading to
discontinuation were reported in 9% of Opdivo-treated patients
(n=44/452) and in 42% of Yervoy-treated patients (n=193/453).
Adverse reactions leading to one or more omitted doses occurred in
28% of patients who received Opdivo. Grade 3 or 4 AEs were
experienced by 25% of patients (n=115/452) in the Opdivo group and
55% of patients (n=250/453) in the Yervoy group. Serious adverse
reactions occurred in 18% of patients treated with Opdivo.1
“Immuno-Oncology has transformed the treatment of metastatic
melanoma and many other cancers over the last decade, and we are
now extending the use of novel agents to help prevent the
recurrence of melanoma,” said Jeffrey S. Weber, M.D., Ph.D., deputy
director of the Laura and Isaac Perlmutter Cancer Center at NYU
Langone Health, and Professor of Medicine at NYU School of
Medicine. “When melanoma has been removed surgically, physicians
and patients alike sometimes struggle with the idea of further
adjuvant treatment because the disease is no longer detectable,
even though it may be likely to return. We recognized a need to
develop new adjuvant treatments with lower toxicity compared to
ipilimumab to help address this challenge. With its impressive
efficacy and broad applicability within stage III and IV melanoma,
nivolumab has the potential to become the next standard of care in
preventing recurrence of melanoma following surgical
resection.”
Bristol-Myers Squibb pioneered the use of immune checkpoint
inhibitors for the adjuvant treatment of melanoma, beginning with
Yervoy. Five-year overall survival data from the Phase 3 CA184-029
trial were recently added to the prescribing information for Yervoy
for the adjuvant treatment of patients with cutaneous melanoma with
pathologic involvement of regional lymph nodes of more than 1 mm
who have undergone complete resection, including total
lymphadenectomy.3 In the trial, 65% of patients treated with Yervoy
were alive at five years, compared with 54% of patients who
received placebo (HR: 0.72; 95% CI: 0.58-0.88; p <0.002).3,7
This analysis was conducted at a median follow-up of 5.3
years.7
“Although there are approved therapies to help prevent melanoma
recurrence, around seven out of 10 patients with stage III disease
do not receive treatment following surgery,” said Valerie Guild,
co-founder and president, AIM at Melanoma Foundation. “As an
advocate, I have witnessed countless times the frustration and fear
patients experience when their cancer returns – even after it was
removed by surgery. Today’s approval offers new hope for people
with melanoma that their disease may not come back.”
About the Pivotal CheckMate -238
Study
CheckMate -238 is an ongoing Phase 3, randomized double-blind
study of Opdivo versus Yervoy in patients who have undergone
complete resection of stage IIIB/C or stage IV melanoma.1,2 The
trial randomized 906 patients 1:1 to receive either Opdivo 3 mg/kg
every two weeks (n=453) or Yervoy 10 mg/kg (n=453) every three
weeks for four doses and then every 12 weeks starting at week 24.1
Patients were treated until disease recurrence, unacceptable
toxicity or consent withdrawal for up to one year. The primary
endpoint is RFS defined as the time between randomization and the
date of first recurrence, new primary melanoma or death. After
meeting the primary endpoint, the trial will continue to evaluate
for overall survival, a secondary endpoint.1 Interim data were
presented at the European Society for Medical Oncology 2017
Congress in Madrid, Spain, with simultaneous publication in The New
England Journal of Medicine.2
Select Safety Profile from the
CheckMate -238 Trial
The most frequent Grade 3 and 4 adverse reactions reported in at
least 2% of Opdivo-treated patients were diarrhea and increased
lipase and amylase. The most common adverse reactions, reported in
at least 20% of Opdivo-treated patients, were fatigue, diarrhea,
rash, musculoskeletal pain, pruritus, headache, nausea, upper
respiratory infection and abdominal pain. The most common
immune-mediated adverse reactions were rash (16%), diarrhea/colitis
(6%) and hepatitis (3%).1
About the CA184-029
Study
The Phase 3 CA184-029 trial, a randomized (1:1), double-blind,
placebo-controlled study, investigated the use of Yervoy for the
adjuvant treatment of melanoma. A total of 951 enrolled patients
with resected stage IIIA (>1 mm nodal involvement), IIIB and
IIIC (with no in-transit metastases) melanoma received either
Yervoy 10 mg/kg (n=475) or placebo (n=476) every three weeks for
four doses, followed by every 12 weeks from week 24 to week 156 or
until documented disease recurrence or unacceptable toxicity. The
major efficacy outcomes were independent review committee-assessed
RFS and OS. Yervoy reduced the risk of recurrence or death by 25%
versus placebo (HR: 0.75; 95% CI: 0.64 to 0.90; p <0.002).
Median RFS was 26 months for Yervoy (95% CI: 19 to 39) and 17
months for placebo (95% CI: 13 to 22). There were 234 RFS events in
the Yervoy arm (49% of patients; 220 recurrences, 14 deaths) and
294 events in the placebo arm (62% of patients; 289 recurrences, 5
deaths).3
Select Safety Profile from the
CA184-029 Trial
In the CA184-029 trial, severe to fatal immune-mediated adverse
reactions were reported, and included enterocolitis (16%),
hepatitis (11%), endocrinopathy (8%), hypopituitarism (7%),
dermatitis (4%), neuropathy (1.7%), hyperthyroidism (0.6%),
meningitis (0.4%), primary hypothyroidism (0.2%), myocarditis
(0.2%), pericarditis (0.2%), pneumonitis (0.2%), and uveitis
(0.2%). The most common adverse reactions were rash (50%), diarrhea
(49%), fatigue (46%), pruritus (45%), headache (33%), weight loss
(32%), nausea (25%), pyrexia (18%), colitis (16%), decreased
appetite (14%), vomiting (13%), and insomnia
(10%). Yervoy was discontinued for adverse reactions in
52% of patients.3
INDICATIONS
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 mutation-positive unresectable
or metastatic melanoma. This indication is approved under
accelerated approval based on progression-free survival. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab),
is indicated for the treatment of patients with unresectable or
metastatic melanoma. This indication is approved under accelerated
approval based on progression-free survival. Continued approval for
this indication may be contingent upon verification and description
of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with metastatic non-small cell lung cancer (NSCLC) with progression
on or after platinum-based chemotherapy. Patients with EGFR or ALK
genomic tumor aberrations should have disease progression on
FDA-approved therapy for these aberrations prior to receiving
OPDIVO.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with advanced renal cell carcinoma (RCC) who have received prior
anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult
patients with classical Hodgkin lymphoma (cHL) that has relapsed or
progressed after autologous hematopoietic stem cell transplantation
(HSCT) and brentuximab vedotin or after 3 or more lines of systemic
therapy that includes autologous HSCT. This indication is approved
under accelerated approval based on overall response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with recurrent or metastatic squamous cell carcinoma of the head
and neck (SCCHN) with disease progression on or after
platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with locally advanced or metastatic urothelial carcinoma who have
disease progression during or following platinum-containing
chemotherapy or have disease progression within 12 months of
neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy. This indication is approved under accelerated
approval based on tumor response rate and duration of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult and
pediatric (12 years and older) patients with microsatellite
instability high (MSI-H) or mismatch repair deficient (dMMR)
metastatic colorectal cancer (CRC) that has progressed following
treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
This indication is approved under accelerated approval based on
overall response rate and duration of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of patients
with hepatocellular carcinoma (HCC) who have been previously
treated with sorafenib. This indication is approved under
accelerated approval based on tumor response rate and durability of
response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of
patients with melanoma with involvement of lymph nodes or
metastatic disease who have undergone complete resection.
OPDIVO (10 mg/mL) is an injection for intravenous (IV) use.
IMPORTANT SAFETY
INFORMATION
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY can result in severe and fatal immune-mediated adverse
reactions. These immune-mediated reactions may involve any organ
system; however, the most common severe immune-mediated adverse
reactions are enterocolitis, hepatitis, dermatitis (including toxic
epidermal necrolysis), neuropathy, and endocrinopathy. The majority
of these immune-mediated reactions initially manifested during
treatment; however, a minority occurred weeks to months after
discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis,
dermatitis, neuropathy, and endocrinopathy and evaluate clinical
chemistries including liver function tests (LFTs),
adrenocorticotropic hormone (ACTH) level, and thyroid function
tests at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic
high-dose corticosteroid therapy for severe immune-mediated
reactions.
Immune-Mediated Pneumonitis
OPDIVO can cause immune-mediated pneumonitis. Fatal cases have
been reported. Monitor patients for signs with radiographic imaging
and for symptoms of pneumonitis. Administer corticosteroids for
Grade 2 or more severe pneumonitis. Permanently discontinue for
Grade 3 or 4 and withhold until resolution for Grade 2. In patients
receiving OPDIVO monotherapy, fatal cases of immune-mediated
pneumonitis have occurred. Immune-mediated pneumonitis occurred in
3.1% (61/1994) of patients. In patients receiving OPDIVO with
YERVOY, immune-mediated pneumonitis occurred in 6% (25/407) of
patients.
In Checkmate 205 and 039, pneumonitis, including interstitial
lung disease, occurred in 6.0% (16/266) of patients receiving
OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of
patients receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=12).
Immune-Mediated Colitis
OPDIVO can cause immune-mediated colitis. Monitor patients for
signs and symptoms of colitis. Administer corticosteroids for Grade
2 (of more than 5 days duration), 3, or 4 colitis. Withhold OPDIVO
monotherapy for Grade 2 or 3 and permanently discontinue for Grade
4 or recurrent colitis upon re-initiation of OPDIVO. When
administered with YERVOY, withhold OPDIVO and YERVOY for Grade 2
and permanently discontinue for Grade 3 or 4 or recurrent colitis.
In patients receiving OPDIVO monotherapy, immune-mediated colitis
occurred in 2.9% (58/1994) of patients. In patients receiving
OPDIVO with YERVOY, immune-mediated colitis occurred in 26%
(107/407) of patients including three fatal cases.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal (diarrhea of ≥7 stools above baseline,
fever, ileus, peritoneal signs; Grade 3-5) immune-mediated
enterocolitis occurred in 34 (7%) patients. Across all
YERVOY-treated patients in that study (n=511), 5 (1%) developed
intestinal perforation, 4 (0.8%) died as a result of complications,
and 26 (5%) were hospitalized for severe enterocolitis.
Immune-Mediated Hepatitis
OPDIVO can cause immune-mediated hepatitis. Monitor patients for
abnormal liver tests prior to and periodically during treatment.
Administer corticosteroids for Grade 2 or greater transaminase
elevations. For patients without HCC, withhold OPDIVO for Grade 2
and permanently discontinue OPDIVO for Grade 3 or 4. For patients
with HCC, withhold OPDIVO and administer corticosteroids if AST/ALT
is within normal limits at baseline and increases to >3 and up
to 5 times the upper limit of normal (ULN), if AST/ALT is >1 and
up to 3 times ULN at baseline and increases to >5 and up to 10
times the ULN, and if AST/ALT is >3 and up to 5 times ULN at
baseline and increases to >8 and up to 10 times the ULN.
Permanently discontinue OPDIVO and administer corticosteroids if
AST or ALT increases to >10 times the ULN or total bilirubin
increases >3 times the ULN. In patients receiving OPDIVO
monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994)
of patients. In patients receiving OPDIVO with YERVOY,
immune-mediated hepatitis occurred in 13% (51/407) of patients.
In Checkmate 040, immune-mediated hepatitis requiring systemic
corticosteroids occurred in 5% (8/154) of patients receiving
OPDIVO.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal hepatotoxicity (AST or ALT elevations
>5x the ULN or total bilirubin elevations >3x the ULN; Grade
3-5) occurred in 8 (2%) patients, with fatal hepatic failure in
0.2% and hospitalization in 0.4%.
Immune-Mediated Neuropathies
In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal
Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral
motor neuropathy were reported.
Immune-Mediated Endocrinopathies
OPDIVO can cause immune-mediated hypophysitis, immune-mediated
adrenal insufficiency, autoimmune thyroid disorders, and Type 1
diabetes mellitus. Monitor patients for signs and symptoms of
hypophysitis, signs and symptoms of adrenal insufficiency, thyroid
function prior to and periodically during treatment, and
hyperglycemia. Administer hormone replacement as clinically
indicated and corticosteroids for Grade 2 or greater hypophysitis.
Withhold for Grade 2 or 3 and permanently discontinue for Grade 4
hypophysitis. Administer corticosteroids for Grade 3 or 4 adrenal
insufficiency. Withhold for Grade 2 and permanently discontinue for
Grade 3 or 4 adrenal insufficiency. Administer hormone-replacement
therapy for hypothyroidism. Initiate medical management for control
of hyperthyroidism. Withhold OPDIVO for Grade 3 and permanently
discontinue for Grade 4 hyperglycemia.
In patients receiving OPDIVO monotherapy, hypophysitis occurred
in 0.6% (12/1994) of patients. In patients receiving OPDIVO with
YERVOY, hypophysitis occurred in 9% (36/407) of patients. In
patients receiving OPDIVO monotherapy, adrenal insufficiency
occurred in 1% (20/1994) of patients. In patients receiving OPDIVO
with YERVOY, adrenal insufficiency occurred in 5% (21/407) of
patients. In patients receiving OPDIVO monotherapy, hypothyroidism
or thyroiditis resulting in hypothyroidism occurred in 9%
(171/1994) of patients. Hyperthyroidism occurred in 2.7% (54/1994)
of patients receiving OPDIVO monotherapy. In patients receiving
OPDIVO with YERVOY, hypothyroidism or thyroiditis resulting in
hypothyroidism occurred in 22% (89/407) of patients.
Hyperthyroidism occurred in 8% (34/407) of patients receiving
OPDIVO with YERVOY. In patients receiving OPDIVO monotherapy,
diabetes occurred in 0.9% (17/1994) of patients. In patients
receiving OPDIVO with YERVOY, diabetes occurred in 1.5% (6/407) of
patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe to
life-threatening immune-mediated endocrinopathies (requiring
hospitalization, urgent medical intervention, or interfering with
activities of daily living; Grade 3-4) occurred in 9 (1.8%)
patients. All 9 patients had hypopituitarism, and some had
additional concomitant endocrinopathies such as adrenal
insufficiency, hypogonadism, and hypothyroidism. 6 of the 9
patients were hospitalized for severe endocrinopathies.
Immune-Mediated Nephritis and Renal Dysfunction
OPDIVO can cause immune-mediated nephritis. Monitor patients for
elevated serum creatinine prior to and periodically during
treatment. Administer corticosteroids for Grades 2-4 increased
serum creatinine. Withhold OPDIVO for Grade 2 or 3 and permanently
discontinue for Grade 4 increased serum creatinine. In patients
receiving OPDIVO monotherapy, immune-mediated nephritis and renal
dysfunction occurred in 1.2% (23/1994) of patients. In patients
receiving OPDIVO with YERVOY, immune-mediated nephritis and renal
dysfunction occurred in 2.2% (9/407) of patients.
Immune-Mediated Skin Adverse Reactions and Dermatitis
OPDIVO can cause immune-mediated rash, including Stevens-Johnson
syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases
with fatal outcome. Administer corticosteroids for Grade 3 or 4
rash. Withhold for Grade 3 and permanently discontinue for Grade 4
rash. For symptoms or signs of SJS or TEN, withhold OPDIVO and
refer the patient for specialized care for assessment and
treatment; if confirmed, permanently discontinue. In patients
receiving OPDIVO monotherapy, immune-mediated rash occurred in 9%
(171/1994) of patients. In patients receiving OPDIVO with YERVOY,
immune-mediated rash occurred in 22.6% (92/407) of patients.
In a separate Phase 3 study of YERVOY 3 mg/kg, severe,
life-threatening, or fatal immune-mediated dermatitis (eg,
Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash
complicated by full thickness dermal ulceration, or necrotic,
bullous, or hemorrhagic manifestations; Grade 3-5) occurred in 13
(2.5%) patients. 1 (0.2%) patient died as a result of toxic
epidermal necrolysis. 1 additional patient required hospitalization
for severe dermatitis.
Immune-Mediated Encephalitis
OPDIVO can cause immune-mediated encephalitis. Evaluation of
patients with neurologic symptoms may include, but not be limited
to, consultation with a neurologist, brain MRI, and lumbar
puncture. Withhold OPDIVO in patients with new-onset moderate to
severe neurologic signs or symptoms and evaluate to rule out other
causes. If other etiologies are ruled out, administer
corticosteroids and permanently discontinue OPDIVO for
immune-mediated encephalitis. In patients receiving OPDIVO
monotherapy, encephalitis occurred in 0.2% (3/1994) of patients.
Fatal limbic encephalitis occurred in one patient after 7.2 months
of exposure despite discontinuation of OPDIVO and administration of
corticosteroids. Encephalitis occurred in one patient receiving
OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.
Other Immune-Mediated Adverse Reactions
Based on the severity of the adverse reaction, permanently
discontinue or withhold OPDIVO, administer high-dose
corticosteroids, and, if appropriate, initiate hormone-replacement
therapy. Across clinical trials of OPDIVO monotherapy or in
combination with YERVOY, the following clinically significant
immune-mediated adverse reactions, some with fatal outcome,
occurred in <1.0% of patients receiving OPDIVO: myocarditis,
rhabdomyolysis, myositis, uveitis, iritis, pancreatitis, facial and
abducens nerve paresis, demyelination, polymyalgia rheumatica,
autoimmune neuropathy, Guillain-Barré syndrome, hypopituitarism,
systemic inflammatory response syndrome, gastritis, duodenitis,
sarcoidosis, histiocytic necrotizing lymphadenitis (Kikuchi
lymphadenitis), motor dysfunction, vasculitis, and myasthenic
syndrome.
Infusion Reactions
OPDIVO can cause severe infusion reactions, which have been
reported in <1.0% of patients in clinical trials. Discontinue
OPDIVO in patients with Grade 3 or 4 infusion reactions. Interrupt
or slow the rate of infusion in patients with Grade 1 or 2. In
patients receiving OPDIVO monotherapy, infusion-related reactions
occurred in 6.4% (127/1994) of patients. In patients receiving
OPDIVO with YERVOY, infusion-related reactions occurred in 2.5%
(10/407) of patients.
Complications of Allogeneic HSCT after OPDIVO
Complications, including fatal events, occurred in patients who
received allogeneic HSCT after OPDIVO. Outcomes were evaluated in
17 patients from Checkmate 205 and 039, who underwent allogeneic
HSCT after discontinuing OPDIVO (15 with reduced-intensity
conditioning, 2 with myeloablative conditioning). Thirty-five
percent (6/17) of patients died from complications of allogeneic
HSCT after OPDIVO. Five deaths occurred in the setting of severe or
refractory GVHD. Grade 3 or higher acute GVHD was reported in 29%
(5/17) of patients. Hyperacute GVHD was reported in 20% (n=2) of
patients. A steroid-requiring febrile syndrome, without an
identified infectious cause, was reported in 35% (n=6) of patients.
Two cases of encephalitis were reported: Grade 3 (n=1) lymphocytic
encephalitis without an identified infectious cause, and Grade 3
(n=1) suspected viral encephalitis. Hepatic veno-occlusive disease
(VOD) occurred in one patient, who received reduced-intensity
conditioned allogeneic HSCT and died of GVHD and multi-organ
failure. Other cases of hepatic VOD after reduced-intensity
conditioned allogeneic HSCT have also been reported in patients
with lymphoma who received a PD-1 receptor blocking antibody before
transplantation. Cases of fatal hyperacute GVHD have also been
reported. These complications may occur despite intervening therapy
between PD-1 blockade and allogeneic HSCT.
Follow patients closely for early evidence of transplant-related
complications such as hyperacute GVHD, severe (Grade 3 to 4) acute
GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other
immune-mediated adverse reactions, and intervene promptly.
Embryo-Fetal Toxicity
Based on their mechanisms of action, OPDIVO and YERVOY can cause
fetal harm when administered to a pregnant woman. Advise pregnant
women of the potential risk to a fetus. Advise females of
reproductive potential to use effective contraception during
treatment with an OPDIVO- or YERVOY- containing regimen and for at
least 5 months after the last dose of OPDIVO.
Lactation
It is not known whether OPDIVO or YERVOY is present in human
milk. Because many drugs, including antibodies, are excreted in
human milk and because of the potential for serious adverse
reactions in nursing infants from an OPDIVO-containing regimen,
advise women to discontinue breastfeeding during treatment. Advise
women to discontinue nursing during treatment with YERVOY and for 3
months following the final dose.
Serious Adverse Reactions
In Checkmate 037, serious adverse reactions occurred in 41% of
patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions
occurred in 42% of patients receiving OPDIVO. The most frequent
Grade 3 and 4 adverse drug reactions reported in 2% to <5% of
patients receiving OPDIVO were abdominal pain, hyponatremia,
increased aspartate aminotransferase, and increased lipase. In
Checkmate 066, serious adverse reactions occurred in 36% of
patients receiving OPDIVO (n=206). Grade 3 and 4 adverse reactions
occurred in 41% of patients receiving OPDIVO. The most frequent
Grade 3 and 4 adverse reactions reported in ≥2% of patients
receiving OPDIVO were gamma-glutamyltransferase increase (3.9%) and
diarrhea (3.4%). In Checkmate 067, serious adverse reactions (73%
and 37%), adverse reactions leading to permanent discontinuation
(43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4
adverse reactions (72% and 44%) all occurred more frequently in the
OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313).
The most frequent (≥10%) serious adverse reactions in the OPDIVO
plus YERVOY arm and the OPDIVO arm, respectively, were diarrhea
(13% and 2.6%), colitis (10% and 1.6%), and pyrexia (10% and 0.6%).
In Checkmate 017 and 057, serious adverse reactions occurred in 46%
of patients receiving OPDIVO (n=418). The most frequent serious
adverse reactions reported in at least 2% of patients receiving
OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia,
pleural effusion, pneumonitis, and respiratory failure. In
Checkmate 025, serious adverse reactions occurred in 47% of
patients receiving OPDIVO (n=406). The most frequent serious
adverse reactions reported in ≥2% of patients were acute kidney
injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia.
In Checkmate 205 and 039, adverse reactions leading to
discontinuation occurred in 7% and dose delays due to adverse
reactions occurred in 34% of patients (n=266). Serious adverse
reactions occurred in 26% of patients. The most frequent serious
adverse reactions reported in ≥1% of patients were pneumonia,
infusion-related reaction, pyrexia, colitis or diarrhea, pleural
effusion, pneumonitis, and rash. Eleven patients died from causes
other than disease progression: 3 from adverse reactions within 30
days of the last OPDIVO dose, 2 from infection 8 to 9 months after
completing OPDIVO, and 6 from complications of allogeneic HSCT. In
Checkmate 141, serious adverse reactions occurred in 49% of
patients receiving OPDIVO (n=236). The most frequent serious
adverse reactions reported in at least 2% of patients receiving
OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory
tract infection, and sepsis. In Checkmate 275, serious adverse
reactions occurred in 54% of patients receiving OPDIVO (n=270). The
most frequent serious adverse reactions reported in at least 2% of
patients receiving OPDIVO were urinary tract infection, sepsis,
diarrhea, small intestine obstruction, and general physical health
deterioration. In Checkmate 040, serious adverse reactions occurred
in 49% of patients (n=154). The most frequent serious adverse
reactions reported in at least 2% of patients were pyrexia,
ascites, back pain, general physical health deterioration,
abdominal pain, and pneumonia. In Checkmate 238, Grade 3 or 4
adverse reactions occurred in 25% of OPDIVO-treated patients
(n=452). The most frequent Grade 3 and 4 adverse reactions reported
in at least 2% of OPDIVO-treated patients were diarrhea and
increased lipase and amylase. Serious adverse reactions occurred in
18% of OPDIVO-treated patients.
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%)
reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the
most common adverse reactions (≥20%) reported with OPDIVO (n=206)
vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal
pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In
Checkmate 067, the most common (≥20%) adverse reactions in the
OPDIVO plus YERVOY arm (n=313) were fatigue (59%), rash (53%),
diarrhea (52%), nausea (40%), pyrexia (37%), vomiting (28%), and
dyspnea (20%). The most common (≥20%) adverse reactions in the
OPDIVO (n=313) arm were fatigue (53%), rash (40%), diarrhea (31%),
and nausea (28%). In Checkmate 017 and 057, the most common adverse
reactions (≥20%) in patients receiving OPDIVO (n=418) were fatigue,
musculoskeletal pain, cough, dyspnea, and decreased appetite. In
Checkmate 025, the most common adverse reactions (≥20%) reported in
patients receiving OPDIVO (n=406) vs everolimus (n=397) were
asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28%
vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs
32%), constipation (23% vs 18%), decreased appetite (23% vs 30%),
back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate
205 and 039, the most common adverse reactions (≥20%) reported in
patients receiving OPDIVO (n=266) were upper respiratory tract
infection (44%), fatigue (39%), cough (36%), diarrhea (33%),
pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%)
and pruritus (20%). In Checkmate 141, the most common adverse
reactions (≥10%) in patients receiving OPDIVO (n=236) were cough
and dyspnea at a higher incidence than investigator’s choice. In
Checkmate 275, the most common adverse reactions (≥ 20%) reported
in patients receiving OPDIVO (n=270) were fatigue (46%),
musculoskeletal pain (30%), nausea (22%), and decreased appetite
(22%). In Checkmate 040, the most common adverse reactions (≥20%)
in patients receiving OPDIVO (n=154) were fatigue (38%),
musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%),
diarrhea (27%), rash (26%), cough (23%), and decreased appetite
(22%). In Checkmate 238, the most common adverse reactions (≥20%)
reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated
patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%),
rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28%
vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper
respiratory infection (22% vs 15%), and abdominal pain (21% vs
23%). The most common immune-mediated adverse reactions were rash
(16%), diarrhea/colitis (6%), and hepatitis (3%). The most common
adverse reactions (≥20%) in patients who received OPDIVO as a
single agent were fatigue, rash, musculoskeletal pain, pruritus,
diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased
appetite, back pain, arthralgia, upper respiratory tract infection,
pyrexia, headache, and abdominal pain.
In a separate Phase 3 study of YERVOY 3 mg/kg, the most common
adverse reactions (≥5%) in patients who received YERVOY at
3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%),
rash (29%), and colitis (8%).
Checkmate 067–advanced melanoma alone or in combination
with YERVOY® (ipilimumab); Checkmate 037 and
066–advanced melanoma; Checkmate 017–squamous non-small
cell lung cancer (NSCLC); Checkmate 057–non-squamous NSCLC;
Checkmate 025–renal cell carcinoma; Checkmate
205/039–classical Hodgkin lymphoma; Checkmate
141–squamous cell carcinoma of the head and neck; Checkmate
275–urothelial carcinoma; Checkmate 040–hepatocellular
carcinoma; Checkmate 238–adjuvant treatment of melanoma
Please see U.S. Full Prescribing Information for OPDIVO and
YERVOY, including Boxed WARNING regarding immune-mediated
adverse reactions for YERVOY.
Indications and Important Safety Information for
YERVOY® (ipilimumab)
Indications
YERVOY® (ipilimumab) is indicated for the adjuvant treatment of
patients with cutaneous melanoma with pathologic involvement of
regional lymph nodes of more than 1 mm who have undergone complete
resection, including total lymphadenectomy.
YERVOY (5 mg/mL) is an injection for intravenous (IV) use.
Important Safety Information
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS
YERVOY (ipilimumab) can result in severe and fatal
immune-mediated adverse reactions. These immune-mediated reactions
may involve any organ system; however, the most common severe
immune-mediated adverse reactions are enterocolitis, hepatitis,
dermatitis (including toxic epidermal necrolysis), neuropathy, and
endocrinopathy. The majority of these immune-mediated reactions
initially manifested during treatment; however, a minority occurred
weeks to months after discontinuation of YERVOY.
Assess patients for signs and symptoms of enterocolitis,
dermatitis, neuropathy, and endocrinopathy and evaluate clinical
chemistries including liver function tests (LFTs),
adrenocorticotropic hormone (ACTH) level, and thyroid function
tests, at baseline and before each dose.
Permanently discontinue YERVOY and initiate systemic
high-dose corticosteroid therapy for severe immune-mediated
reactions.
Recommended Dose Modifications
Endocrine: Withhold YERVOY for symptomatic endocrinopathy.
Resume YERVOY in patients with complete or partial resolution of
adverse reactions (Grade 0-1) and who are receiving <7.5 mg
prednisone or equivalent per day. Permanently discontinue YERVOY
for symptomatic reactions lasting 6 weeks or longer or an inability
to reduce corticosteroid dose to 7.5 mg prednisone or equivalent
per day.
Ophthalmologic: Permanently discontinue YERVOY for Grade 2-4
reactions not improving to Grade 1 within 2 weeks while receiving
topical therapy or requiring systemic treatment.
All Other Organ Systems: Withhold YERVOY for Grade 2 adverse
reactions. Resume YERVOY in patients with complete or partial
resolution of adverse reactions (Grade 0-1) and who are receiving
<7.5 mg prednisone or equivalent per day. Permanently
discontinue YERVOY for Grade 2 reactions lasting 6 weeks or longer,
an inability to reduce corticosteroid dose to 7.5 mg prednisone or
equivalent per day, and Grade 3 or 4 adverse reactions.
Immune-mediated Enterocolitis
Immune-mediated enterocolitis, including fatal cases, can occur
with YERVOY. Monitor patients for signs and symptoms of
enterocolitis (such as diarrhea, abdominal pain, mucus or blood in
stool, with or without fever) and of bowel perforation (such as
peritoneal signs and ileus). In symptomatic patients, rule out
infectious etiologies and consider endoscopic evaluation for
persistent or severe symptoms.
Withhold YERVOY for moderate enterocolitis; administer
anti-diarrheal treatment and, if persistent for >1 week,
initiate systemic corticosteroids (0.5 mg/kg/day prednisone or
equivalent). Permanently discontinue YERVOY in patients with severe
enterocolitis and initiate systemic corticosteroids (1-2 mg/kg/day
of prednisone or equivalent). Upon improvement to ≤Grade 1,
initiate corticosteroid taper and continue over at least 1 month.
In clinical trials, rapid corticosteroid tapering resulted in
recurrence or worsening symptoms of enterocolitis in some patients.
Consider adding anti-TNF or other immunosuppressant agents for
management of immune-mediated enterocolitis unresponsive to
systemic corticosteroids within 3-5 days or recurring after symptom
improvement. In patients receiving YERVOY 10 mg/kg in Trial 2,
Grade 3-5 immune-mediated enterocolitis occurred in 76 patients
(16%) and Grade 2 enterocolitis occurred in 68 patients (14%).
Seven (1.5%) developed intestinal perforation and 3 patients (0.6%)
died as a result of complications.
Immune-mediated Hepatitis
Immune-mediated hepatitis, including fatal cases, can occur with
YERVOY. Monitor LFTs (hepatic transaminase and bilirubin levels)
and assess patients for signs and symptoms of hepatotoxicity before
each dose of YERVOY. In patients with hepatotoxicity, rule out
infectious or malignant causes and increase frequency of LFT
monitoring until resolution. Withhold YERVOY in patients with Grade
2 hepatotoxicity. Permanently discontinue YERVOY in patients with
Grade 3-4 hepatotoxicity and administer systemic corticosteroids
(1-2 mg/kg/day of prednisone or equivalent). When LFTs show
sustained improvement or return to baseline, initiate
corticosteroid tapering and continue over 1 month. Across the
clinical development program for YERVOY, mycophenolate treatment
has been administered in patients with persistent severe hepatitis
despite high-dose corticosteroids. In patients receiving YERVOY 10
mg/kg in Trial 2, Grade 3-4 immune-mediated hepatitis occurred in
51 patients (11%) and moderate Grade 2 immune-mediated hepatitis
occurred in 22 patients (5%). Liver biopsy performed in 6 patients
with Grade 3-4 hepatitis showed evidence of toxic or autoimmune
hepatitis.
Immune-mediated Dermatitis
Immune-mediated dermatitis, including fatal cases, can occur
with YERVOY. Monitor patients for signs and symptoms of dermatitis
such as rash and pruritus. Unless an alternate etiology has been
identified, signs or symptoms of dermatitis should be considered
immune-mediated. Treat mild to moderate dermatitis (e.g., localized
rash and pruritus) symptomatically; administer topical or systemic
corticosteroids if there is no improvement within 1 week. Withhold
YERVOY in patients with moderate to severe signs and symptoms.
Permanently discontinue YERVOY in patients with severe, life-
threatening, or fatal immune-mediated dermatitis (Grade 3-5).
Administer systemic corticosteroids (1-2 mg/kg/day of prednisone or
equivalent). When dermatitis is controlled, corticosteroid tapering
should occur over a period of at least 1 month. In patients
receiving YERVOY 10 mg/kg in Trial 2, Grade 3-4 immune-mediated
dermatitis occurred in 19 patients (4%). There were 99 patients
(21%) with moderate Grade 2 dermatitis.
Immune-mediated Neuropathies
Immune-mediated neuropathies, including fatal cases, can occur
with YERVOY. Monitor for symptoms of motor or sensory neuropathy
such as unilateral or bilateral weakness, sensory alterations, or
paresthesia. Withhold YERVOY in patients with moderate neuropathy
(not interfering with daily activities). Permanently discontinue
YERVOY in patients with severe neuropathy (interfering with daily
activities), such as Guillain-Barre-like syndromes. Institute
medical intervention as appropriate for management for severe
neuropathy. Consider initiation of systemic corticosteroids (1-2
mg/kg/day of prednisone or equivalent) for severe neuropathies. In
patients receiving YERVOY 10 mg/kg in Trial 2, Grade 3-5
immune-mediated neuropathy occurred in 8 patients (2%); the sole
fatality was due to complications of Guillain-Barré syndrome.
Moderate Grade 2 immune-mediated neuropathy occurred in 1 patient
(0.2%).
Immune-mediated Endocrinopathies
Immune-mediated endocrinopathies, including life-threatening
cases, can occur with YERVOY. Monitor patients for clinical signs
and symptoms of hypophysitis, adrenal insufficiency (including
adrenal crisis), and hyper- or hypothyroidism. Patients may present
with fatigue, headache, mental status changes, abdominal pain,
unusual bowel habits, and hypotension, or nonspecific symptoms
which may resemble other causes such as brain metastasis or
underlying disease. Unless an alternate etiology has been
identified, signs or symptoms should be considered immune-mediated.
Monitor clinical chemistries, adrenocorticotropic hormone (ACTH)
level, and thyroid function tests at the start of treatment, before
each dose, and as clinically indicated based on symptoms. In a
limited number of patients, hypophysitis was diagnosed by imaging
studies through enlargement of the pituitary gland.
Withhold YERVOY in symptomatic patients and consider referral to
an endocrinologist. Initiate systemic corticosteroids (1-2
mg/kg/day of prednisone or equivalent) and initiate appropriate
hormone replacement therapy. In patients receiving YERVOY 10 mg/kg
in Trial 2, Grade 3-4 immune-mediated endocrinopathies occurred in
39 patients (8%) and Grade 2 immune-mediated endocrinopathies
occurred in 93 patients (20%). Of the 39 patients with Grade 3-4
immune-mediated endocrinopathies, 35 patients had hypopituitarism
(associated with 1 or more secondary endocrinopathies, e.g.,
adrenal insufficiency, hypogonadism, and hypothyroidism), 3
patients had hyperthyroidism, and 1 had primary hypothyroidism. The
median time to onset of Grade 3-4 immune-mediated endocrinopathy
was 2.2 months (range: 2 days-8 months). Twenty-seven (69.2%) of
the 39 patients were hospitalized for immune-mediated
endocrinopathies. Of the 93 patients with Grade 2 immune-mediated
endocrinopathy, 74 had primary hypopituitarism (associated with 1
or more secondary endocrinopathy, e.g., adrenal insufficiency,
hypogonadism, and hypothyroidism), 9 had primary hypothyroidism, 3
had hyperthyroidism, 3 had thyroiditis with hypo- or
hyperthyroidism, 2 had hypogonadism, 1 had both hyperthyroidism and
hypopituitarism, and 1 subject developed Graves’ ophthalmopathy.
The median time to onset of Grade 2 immune-mediated endocrinopathy
was 2.1 months (range: 9 days-19.3 months).
Other Immune-mediated Adverse Reactions, Including Ocular
Manifestations
Permanently discontinue YERVOY for clinically significant or
severe immune-mediated adverse reactions. Initiate systemic
corticosteroids (1-2 mg/kg/day of prednisone or equivalent) for
severe immune-mediated adverse reactions. Administer corticosteroid
eye drops for uveitis, iritis, or episcleritis. Permanently
discontinue YERVOY for immune-mediated ocular disease unresponsive
to local immunosuppressive therapy. If uveitis occurs in
combination with other immune-mediated adverse reactions, consider
a Vogt-Koyanagi-Harada-like syndrome, which has been observed in
patients receiving YERVOY and may require treatment with systemic
steroids to reduce the risk of permanent vision loss. In Trial 2,
the following clinically significant immune-mediated adverse
reactions were seen in <1% of YERVOY-treated patients unless
specified: eosinophilia (2.1%), pancreatitis (1.3%), meningitis,
pneumonitis, sarcoidosis, pericarditis, uveitis and fatal
myocarditis.
Across 21 dose-ranging trials administering YERVOY at doses of
0.1 to 20 mg/kg (n=2478), the following likely immune-mediated
adverse reactions were also reported with <1% incidence:
angiopathy, temporal arteritis, vasculitis, polymyalgia rheumatica,
conjunctivitis, blepharitis, episcleritis, scleritis, iritis,
leukocytoclastic vasculitis, erythema multiforme, psoriasis,
arthritis, autoimmune thyroiditis, neurosensory hypoacusis,
autoimmune central neuropathy (encephalitis), myositis,
polymyositis, ocular myositis, hemolytic anemia, and nephritis.
Embryo-fetal Toxicity
Based on its mechanism of action, YERVOY can cause fetal harm
when administered to a pregnant woman. The effects of YERVOY are
likely to be greater during the second and third trimesters of
pregnancy. Advise pregnant women of the potential risk to a fetus.
Advise females of reproductive potential to use effective
contraception during treatment with a YERVOY-containing regimen and
for 3 months after the last dose of YERVOY.
Lactation
It is not known whether YERVOY is secreted in human milk. Advise
women to discontinue nursing during treatment with YERVOY and for 3
months following the final dose.
Common Adverse Reactions
The most common adverse reactions (≥5%) in patients who received
YERVOY at 10 mg/kg were rash (50%), diarrhea (49%), fatigue (46%),
pruritus (45%), headache (33%), weight loss (32%), nausea (25%),
pyrexia (18%), colitis (16%), decreased appetite (14%), vomiting
(13%), and insomnia (10%).
Please see U.S. Full Prescribing Information, including Boxed
WARNING regarding immune- mediated adverse reactions.
About the Opdivo Clinical
Development Program
Bristol-Myers Squibb’s global development program is founded on
scientific expertise in the field of Immuno-Oncology and includes a
broad range of clinical trials studying Opdivo, across
all phases, including Phase 3, in a variety of tumor types. To
date, the Opdivo clinical development program has
enrolled more than 25,000 patients.
Bristol-Myers Squibb &
Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of
everything we do. Our vision for the future of cancer care is
focused on researching and developing transformational
Immuno-Oncology (I-O) medicines for hard-to-treat cancers that
could potentially improve outcomes for these patients.
We are leading the scientific understanding of I-O through our
extensive portfolio of investigational compounds and approved
agents. Our differentiated clinical development program is studying
broad patient populations across more than 50 types of cancers with
14 clinical-stage molecules designed to target different immune
system pathways. Our deep expertise and innovative clinical trial
designs position us to advance I-O/I-O, I-O/chemotherapy,
I-O/targeted therapies and I-O radiation therapies across multiple
tumors and potentially deliver the next wave of therapies with a
sense of urgency. We also continue to pioneer research that will
help facilitate a deeper understanding of the role of immune
biomarkers and how patients’ tumor biology can be used as a guide
for treatment decisions throughout their journey.
We understand making the promise of I-O a reality for the many
patients who may benefit from these therapies requires not only
innovation on our part but also close collaboration with leading
experts in the field. Our partnerships with academia, government,
advocacy and biotech companies support our collective goal of
providing new treatment options to advance the standards of
clinical practice.
About Bristol-Myers Squibb’s Patient
Access Support
Bristol-Myers Squibb remains committed to providing assistance
so that cancer patients who need our medicines can access them and
expedite time to therapy.
BMS Access Support®, the Bristol-Myers Squibb patient access and
reimbursement program, is designed to help appropriate patients
initiate and maintain access to BMS medicines during their
treatment journey. BMS Access Support offers benefit investigation,
prior authorization assistance and co-pay assistance for eligible,
commercially insured patients. More information about our access
and reimbursement support can be obtained by calling BMS Access
Support® at 1-800-861-0048 or by visiting
www.bmsaccesssupport.com.
About the Bristol-Myers Squibb and Ono
Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono
Pharmaceutical Co., Bristol-Myers Squibb expanded its territorial
rights to develop and commercialize Opdivo globally
except in Japan, South Korea and Taiwan, where Ono had retained all
rights to the compound at the time. On July 23, 2014, Ono and
Bristol-Myers Squibb further expanded the companies’ strategic
collaboration agreement to jointly develop and commercialize
multiple immunotherapies – as single agents and combination
regimens – for patients with cancer in Japan, South Korea and
Taiwan.
About Bristol-Myers
Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose
mission is to discover, develop and deliver innovative medicines
that help patients prevail over serious diseases. For more
information about Bristol-Myers Squibb, visit us at BMS.com or
follow us on LinkedIn, Twitter, YouTube and Facebook.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains “forward-looking statements” as that
term is defined in the Private Securities Litigation Reform Act of
1995 regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based
on current expectations and involve inherent risks and
uncertainties, including factors that could delay, divert or change
any of them, and could cause actual outcomes and results to differ
materially from current expectations. No forward-looking statement
can be guaranteed. Forward-looking statements in this press release
should be evaluated together with the many uncertainties that
affect Bristol-Myers Squibb’s business, particularly those
identified in the cautionary factors discussion in Bristol-Myers
Squibb’s Annual Report on Form 10-K for the year ended December 31,
2016 in our Quarterly Reports on Form 10-Q and our Current Reports
on Form 8-K. Bristol-Myers Squibb undertakes no obligation to
publicly update any forward-looking statement, whether as a result
of new information, future events or otherwise.
###
Referenced with permission from NCCN Clinical Practice
Guidelines in Oncology (NCCN Guidelines®) for Melanoma Version
1.2018. ©National Comprehensive Cancer Network, Inc. 2017. All
rights reserved. Accessed October 23, 2017. To view the most recent
and complete version of the guideline, go online to NCCN.org.
The National Comprehensive Cancer Network makes no warranties of
any kind whatsoever regarding their content, use or application and
disclaims any responsibility for their application or use in any
way.
References
- Opdivo Prescribing Information. Opdivo
U.S. Product Information. Last updated: December 2017. Princeton,
NJ: Bristol-Myers Squibb Company.
- Weber J, Mandala M, Del Vecchio M, et
al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or
IV Melanoma. N Engl J Med. 2017 Nov 9; 377(19):1824-1835.
- Yervoy Prescribing Information. Yervoy
U.S. Product Information. Last updated: December 2017 Princeton,
NJ: Bristol-Myers Squibb Company.
- Harlan LC, Lynch CF, Ballard-Barbash R,
Zeruto C. Trends in the Treatment and Survival for Local and
Regional Cutaneous Melanoma in a US Population-Based
Study. Melanoma Res. 2011 Dec; 21(6):547-54.
- Romano, E., Scordo, M., Dusza, S.,
Coit, D. and Chapman, P. Site and Timing of First Relapse in Stage
III Melanoma Patients: Implications for Follow-Up
Guidelines. J Clin Oncol. 2010; 28(18), pp.3042-3047.
- National Comprehensive Cancer Network
Clinical Practice Guidelines in Oncology. Melanoma. October 11,
2017.
- Eggermont, A, Chiarion-Sileni V, Grob
J, et al. Prolonged Survival in Stage III Melanoma with Ipilimumab
Adjuvant Therapy. N Engl J Med. 2016 Nov 10; 375:1845-1855.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20171220006026/en/
Bristol-Myers SquibbMedia:Laurel Sacks,
609-302-5456Cell:
917-861-0746laurel.sacks@bms.comorInvestors:Tim Power,
609-252-7509timothy.power@bms.comorBill Szablewski,
609-252-5894william.szablewski@bms.com
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Mar 2024 to Apr 2024
Bristol Myers Squibb (NYSE:BMY)
Historical Stock Chart
From Apr 2023 to Apr 2024