With Pivotal KEYNOTE-181 Trial Meeting
Primary Endpoint of OS, KEYTRUDA Becomes the First Anti-PD-1
Therapy to Demonstrate a Survival Benefit for These
Patients
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, announced today that the Phase 3 KEYNOTE-181 trial
investigating KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy
in the second-line treatment of advanced or metastatic esophageal
or esophagogastric junction carcinoma has met a primary endpoint of
overall survival (OS) in patients whose tumors expressed PD-L1
(Combined Positive Score [CPS] ≥10). In this pivotal study,
treatment with KEYTRUDA resulted in a statistically significant
improvement in OS compared to chemotherapy (paclitaxel, docetaxel
or irinotecan) in patients with CPS ≥10, regardless of histology.
The primary endpoint of OS was also evaluated in patients with
squamous cell histology and in the entire intention-to-treat (ITT)
study population. While directionally favorable, statistical
significance for OS was not met in these two patient groups. Per
the statistical analysis plan, the key secondary endpoints of
progression-free survival (PFS) and objective response rate (ORR)
were not formally tested, as OS was not reached in the full ITT
study population. The safety profile of KEYTRUDA in this trial was
consistent with that observed in previously reported studies.
Results will be presented at an upcoming medical meeting and will
be submitted to regulatory authorities worldwide.
“In this pivotal trial, KEYTRUDA resulted in a statistically
significant and clinically meaningful improvement over standard
chemotherapy in overall survival for patients with advanced
esophageal or esophagogastric junction carcinoma whose tumors
express PD-L1 with a CPS of 10 or greater. This marks the sixth
tumor type where KEYTRUDA has demonstrated a survival benefit, and
represents the first time an anti-PD-1 therapy has achieved overall
survival for this patient population,” said Dr. Roy Baynes, senior
vice president and head of global clinical development, chief
medical officer, Merck Research Laboratories. “We are encouraged by
these results of KEYTRUDA as monotherapy in previously-treated
patients, and look forward to continuing our research efforts in
this significant area of unmet need with our ongoing Phase 3 trial,
KEYNOTE-590, evaluating KEYTRUDA in combination with chemotherapy
as a first-line treatment for patients with esophageal
carcinoma.”
About KEYNOTE-181KEYNOTE-181 is a randomized, open-label,
Phase 3 trial (ClinicalTrials.gov, NCT02564263) investigating
KEYTRUDA monotherapy compared to chemotherapy in patients with
advanced or metastatic adenocarcinoma or squamous cell carcinoma of
the esophagus, or Siewert type I adenocarcinoma of the
esophagogastric junction that has progressed after first-line
standard therapy. The primary endpoint was OS (evaluated in all
patients as well as in patients with PD-L1 CPS ≥10 and in patients
with squamous cell carcinoma). Secondary endpoints were PFS, ORR
and safety/tolerability. The study enrolled more than 600 patients
who were randomized 1:1 to receive either KEYTRUDA (200 mg fixed
dose every three weeks) or investigator’s choice of any of the
following chemotherapy regimens, all given intravenously: docetaxel
(75 mg/m^2 on Day 1 of each 21-day cycle), paclitaxel (80-100
mg/m^2 on Days 1, 8, and 15 of each 28-day cycle), or irinotecan
(80 mg/m^2 on Day 1 of each 14-day cycle).
About Esophageal CancerEsophageal cancer, a type of
cancer that is particularly difficult to treat, begins in the inner
layer (mucosa) of the esophagus and grows outward. There are two
main types of esophageal cancer: squamous cell carcinoma and
adenocarcinoma. Globally, esophageal cancer is the seventh most
commonly diagnosed cancer. This year, an estimated 17,290 adults in
the United States will be diagnosed with esophageal cancer, and
15,850 deaths from this disease will occur. Worldwide, there are
estimated to be over 572,000 new cases of esophageal cancer and
approximately 508,000 deaths resulting from this disease in 2018
alone.
About KEYTRUDA® (pembrolizumab) Injection,
100mgKEYTRUDA is an anti-PD-1 therapy that works by increasing
the ability of the body’s immune system to help detect and fight
tumor cells. KEYTRUDA is a humanized monoclonal antibody that
blocks the interaction between PD-1 and its ligands, PD-L1 and
PD-L2, thereby activating T lymphocytes which may affect both tumor
cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical
research program. There are currently more than 850 trials studying
KEYTRUDA across a wide variety of cancers and treatment settings.
The KEYTRUDA clinical program seeks to understand the role of
KEYTRUDA across cancers and the factors that may predict a
patient’s likelihood of benefitting from treatment with KEYTRUDA,
including exploring several different biomarkers.
KEYTRUDA® (pembrolizumab) Indications and
Dosing
MelanomaKEYTRUDA is indicated for the treatment of patients with
unresectable or metastatic melanoma at a fixed dose of 200 mg every
three weeks until disease progression or unacceptable toxicity.
Lung CancerKEYTRUDA, in combination with pemetrexed and platinum
chemotherapy, is indicated for the first-line treatment of patients
with metastatic nonsquamous non-small cell lung cancer (NSCLC),
with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel
or nab-paclitaxel, is indicated for the first-line treatment of
patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line
treatment of patients with metastatic non-small cell lung cancer
(NSCLC) whose tumors have high PD-L1 expression [Tumor Proportion
Score (TPS) ≥50%] as determined by an FDA-approved test, with no
EGFR or ALK genomic tumor aberrations.
KEYTRUDA, as a single agent, is indicated for the treatment of
patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%)
as determined by an FDA-approved test, with disease progression on
or after platinum-containing chemotherapy. Patients with EGFR or
ALK genomic tumor aberrations should have disease progression on
FDA-approved therapy for these aberrations prior to receiving
KEYTRUDA.
In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of
200 mg every three weeks until disease progression, unacceptable
toxicity, or up to 24 months in patients without disease
progression.
When administering KEYTRUDA in combination with chemotherapy,
KEYTRUDA should be administered prior to chemotherapy when given on
the same day. See also the Prescribing Information for the
chemotherapy agents administered in combination with KEYTRUDA, as
appropriate.
Head and Neck CancerKEYTRUDA is indicated for the treatment of
patients with recurrent or metastatic head and neck squamous cell
carcinoma (HNSCC) with disease progression on or after
platinum-containing chemotherapy. 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. In HNSCC, KEYTRUDA is administered at a fixed
dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without
disease progression.
Classical Hodgkin LymphomaKEYTRUDA is indicated for the
treatment of adult and pediatric patients with refractory classical
Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior
lines of therapy. 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. In adults with cHL, KEYTRUDA is administered
at a fixed dose of 200 mg every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in
patients without disease progression. In pediatric patients with
cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum
of 200 mg) every three weeks until disease progression or
unacceptable toxicity, or up to 24 months in patients without
disease progression.
Primary Mediastinal Large B-Cell LymphomaKEYTRUDA is indicated
for the treatment of adult and pediatric patients with refractory
primary mediastinal large B-cell lymphoma (PMBCL), or who have
relapsed after 2 or more prior lines of therapy. 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 confirmatory trials. KEYTRUDA is not recommended for the
treatment of patients with PMBCL who require urgent cytoreductive
therapy.
In adults with PMBCL, KEYTRUDA is administered at a fixed dose
of 200 mg every three weeks until disease progression, unacceptable
toxicity, or up to 24 months in patients without disease
progression. In pediatric patients with PMBCL, KEYTRUDA is
administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every
three weeks until disease progression or unacceptable toxicity, or
up to 24 months in patients without disease progression.
Urothelial CarcinomaKEYTRUDA is indicated for the treatment of
patients with locally advanced or metastatic urothelial carcinoma
(mUC) who are not eligible for cisplatin-containing chemotherapy
and whose tumors express PD-L1 [Combined Positive Score (CPS) ≥10]
as determined by an FDA-approved test, or in patients who are not
eligible for any platinum-containing chemotherapy regardless of
PD-L1 status. 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 the
confirmatory trials.
KEYTRUDA is indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma (mUC) who have disease
progression during or following platinum-containing chemotherapy or
within 12 months of neoadjuvant or adjuvant treatment with
platinum-containing chemotherapy.
In locally advanced or metastatic urothelial carcinoma, KEYTRUDA
is administered at a fixed dose of 200 mg every three weeks until
disease progression or unacceptable toxicity, or up to 24 months in
patients without disease progression.
Microsatellite Instability-High (MSI-H) CancerKEYTRUDA is
indicated for the treatment of adult and pediatric patients with
unresectable or metastatic microsatellite instability-high (MSI-H)
or mismatch repair deficient (dMMR)
- solid tumors that have progressed
following prior treatment and who have no satisfactory alternative
treatment options, or
- colorectal cancer that has progressed
following treatment with fluoropyrimidine, oxaliplatin, and
irinotecan.
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. The
safety and effectiveness of KEYTRUDA in pediatric patients with
MSI-H central nervous system cancers have not been established.
In adult patients with MSI-H cancer, KEYTRUDA is administered at
a fixed dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without
disease progression. In children with MSI-H cancer, KEYTRUDA is
administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every
three weeks until disease progression or unacceptable toxicity, or
up to 24 months in patients without disease progression.
Gastric CancerKEYTRUDA is indicated for the treatment of
patients with recurrent locally advanced or metastatic gastric or
gastroesophageal junction (GEJ) adenocarcinoma whose tumors express
PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an
FDA-approved test, with disease progression on or after two or more
prior lines of therapy including fluoropyrimidine- and
platinum-containing chemotherapy and if appropriate,
HER2/neu-targeted therapy. 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. The recommended dose of KEYTRUDA is a fixed
dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without
disease progression.
Cervical CancerKEYTRUDA is indicated for the treatment of
patients with recurrent or metastatic cervical cancer with disease
progression on or after chemotherapy whose tumors express PD-L1
(CPS ≥1) as determined by an FDA-approved test. 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. The recommended dose of
KEYTRUDA is a fixed dose of 200 mg every three weeks until disease
progression, unacceptable toxicity, or up to 24 months in patients
without disease progression.
Hepatocellular CarcinomaKEYTRUDA 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. The recommended dose of KEYTRUDA is a
fixed dose of 200 mg every three weeks until disease progression,
unacceptable toxicity, or up to 24 months in patients without
disease progression.
Selected Important Safety Information for KEYTRUDA
Immune-Mediated PneumonitisKEYTRUDA can cause
immune-mediated pneumonitis, including fatal cases. Pneumonitis
occurred in 3.4% (94/2799) of patients receiving KEYTRUDA,
including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5
(0.1%), and occurred more frequently in patients with a history of
prior thoracic radiation (6.9%) compared to those without (2.9%).
Monitor patients for signs and symptoms of pneumonitis. Evaluate
suspected pneumonitis with radiographic imaging. Administer
corticosteroids for Grade 2 or greater pneumonitis. Withhold
KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3
or 4 or recurrent Grade 2 pneumonitis.
Immune-Mediated ColitisKEYTRUDA can cause immune-mediated
colitis. Colitis occurred in 1.7% (48/2799) of patients receiving
KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%).
Monitor patients for signs and symptoms of colitis. Administer
corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA
for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4
colitis.
Immune-Mediated HepatitisKEYTRUDA can cause
immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of
patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%),
and 4 (<0.1%). Monitor patients for changes in liver function.
Administer corticosteroids for Grade 2 or greater hepatitis and,
based on severity of liver enzyme elevations, withhold or
discontinue KEYTRUDA.
Immune-Mediated EndocrinopathiesKEYTRUDA can cause
hypophysitis, thyroid disorders, and type 1 diabetes mellitus.
Hypophysitis occurred in 0.6% (17/2799) of patients, including
Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred
in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3
(0.1%). The incidence of new or worsening hypothyroidism was higher
in patients with HNSCC occurring in 15% (28/192) of patients.
Hyperthyroidism occurred in 3.4% (96/2799) of patients, including
Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6%
(16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes
mellitus, including diabetic ketoacidosis, occurred in 0.2%
(6/2799) of patients.
Monitor patients for signs and symptoms of hypophysitis
(including hypopituitarism and adrenal insufficiency), thyroid
function (prior to and periodically during treatment), and
hyperglycemia. For hypophysitis, administer corticosteroids and
hormone replacement as clinically indicated. Withhold KEYTRUDA for
Grade 2 and withhold or discontinue for Grade 3 or 4 hypophysitis.
Administer hormone replacement for hypothyroidism and manage
hyperthyroidism with thionamides and beta-blockers as appropriate.
Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.
Administer insulin for type 1 diabetes, and withhold KEYTRUDA and
administer antihyperglycemics in patients with severe
hyperglycemia.
Immune-Mediated Nephritis and Renal DysfunctionKEYTRUDA
can cause immune-mediated nephritis. Nephritis occurred in 0.3%
(9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%),
3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7%
(7/405) of patients receiving KEYTRUDA in combination with
pemetrexed and platinum chemotherapy. Monitor patients for changes
in renal function. Administer corticosteroids for Grade 2 or
greater nephritis. Withhold KEYTRUDA for Grade 2; permanently
discontinue for Grade 3 or 4 nephritis.
Immune-Mediated Skin ReactionsImmune-mediated rashes,
including Stevens-Johnson syndrome (SJS), toxic epidermal
necrolysis (TEN) (some cases with fatal outcome), exfoliative
dermatitis, and bullous pemphigoid, can occur. Monitor patients for
suspected severe skin reactions and based on the severity of the
adverse reaction, withhold or permanently discontinue KEYTRUDA and
administer corticosteroids. For signs or symptoms of SJS or TEN,
withhold KEYTRUDA and refer the patient for specialized care for
assessment and treatment. If SJS or TEN is confirmed, permanently
discontinue KEYTRUDA.
Other Immune-Mediated Adverse ReactionsImmune-mediated
adverse reactions, which may be severe or fatal, can occur in any
organ system or tissue in patients receiving KEYTRUDA and may also
occur after discontinuation of treatment. For suspected
immune-mediated adverse reactions, ensure adequate evaluation to
confirm etiology or exclude other causes. Based on the severity of
the adverse reaction, withhold KEYTRUDA and administer
corticosteroids. Upon improvement to Grade 1 or less, initiate
corticosteroid taper and continue to taper over at least 1 month.
Based on limited data from clinical studies in patients whose
immune-related adverse reactions could not be controlled with
corticosteroid use, administration of other systemic
immunosuppressants can be considered. Resume KEYTRUDA when the
adverse reaction remains at Grade 1 or less following
corticosteroid taper. Permanently discontinue KEYTRUDA for any
Grade 3 immune-mediated adverse reaction that recurs and for any
life-threatening immune-mediated adverse reaction.
The following clinically significant immune-mediated adverse
reactions occurred in less than 1% (unless otherwise indicated) of
2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barré
syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic
anemia, sarcoidosis, and encephalitis. In addition, myelitis and
myocarditis were reported in other clinical trials and
postmarketing use.
Treatment with KEYTRUDA may increase the risk of rejection in
solid organ transplant recipients. Consider the benefit of
treatment vs the risk of possible organ rejection in these
patients.
Infusion-Related ReactionsKEYTRUDA can cause severe or
life-threatening infusion-related reactions, including
hypersensitivity and anaphylaxis, which have been reported in 0.2%
(6/2799) of patients. Monitor patients for signs and symptoms of
infusion-related reactions. For Grade 3 or 4 reactions, stop
infusion and permanently discontinue KEYTRUDA.
Complications of Allogeneic Hematopoietic Stem Cell
Transplantation (HSCT)Immune-mediated complications, including
fatal events, occurred in patients who underwent allogeneic HSCT
after treatment with KEYTRUDA. Of 23 patients with cHL who
proceeded to allogeneic HSCT after KEYTRUDA, 6 developed
graft-versus-host disease (GVHD) (1 fatal case) and 2 developed
severe hepatic veno-occlusive disease (VOD) after reduced-intensity
conditioning (1 fatal case). Cases of fatal hyperacute GVHD after
allogeneic HSCT have also been reported in patients with lymphoma
who received a PD-1 receptor–blocking antibody before
transplantation. Follow patients closely for early evidence of
transplant-related complications such as hyperacute
graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD,
steroid-requiring febrile syndrome, hepatic veno-occlusive disease
(VOD), and other immune-mediated adverse reactions.
In patients with a history of allogeneic HSCT, acute GVHD
(including fatal GVHD) has been reported after treatment with
KEYTRUDA. Patients who experienced GVHD after their transplant
procedure may be at increased risk for GVHD after KEYTRUDA.
Consider the benefit of KEYTRUDA vs the risk of GVHD in these
patients.
Increased Mortality in Patients With Multiple MyelomaIn
clinical trials in patients with multiple myeloma, the addition of
KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in
increased mortality. Treatment of these patients with a PD-1 or
PD-L1 blocking antibody in this combination is not recommended
outside of controlled clinical trials.
Embryofetal ToxicityBased on its mechanism of action,
KEYTRUDA can cause fetal harm when administered to a pregnant
woman. If used during pregnancy, or if the patient becomes pregnant
during treatment, apprise the patient of the potential hazard to a
fetus. Advise females of reproductive potential to use highly
effective contraception during treatment and for 4 months after the
last dose of KEYTRUDA.
Adverse ReactionsIn KEYNOTE-006, KEYTRUDA was
discontinued due to adverse reactions in 9% of 555 patients with
advanced melanoma; adverse reactions leading to permanent
discontinuation in more than one patient were colitis (1.4%),
autoimmune hepatitis (0.7%), allergic reaction (0.4%),
polyneuropathy (0.4%), and cardiac failure (0.4%). The most common
adverse reactions (≥20%) with KEYTRUDA were fatigue (28%), diarrhea
(26%), rash (24%), and nausea (21%).
In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed
and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA
was discontinued due to adverse reactions in 20% of 405 patients.
The most common adverse reactions resulting in permanent
discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney
injury (2%). The most common adverse reactions (≥20%) with KEYTRUDA
were nausea (56%), fatigue (56%), constipation (35%), diarrhea
(31%), decreased appetite (28%), rash (25%), vomiting (24%), cough
(21%), dyspnea (21%), and pyrexia (20%).
In KEYNOTE-407, when KEYTRUDA was administered with carboplatin
and either paclitaxel or nab-paclitaxel in metastatic squamous
NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of
101 patients. The most frequent serious adverse reactions reported
in at least 2% of patients were febrile neutropenia, pneumonia, and
urinary tract infection. Adverse reactions observed in KEYNOTE-407
were similar to those observed in KEYNOTE-189 with the exception
that increased incidences of alopecia (47% vs 36%) and peripheral
neuropathy (31% vs 25%) were observed in the KEYTRUDA and
chemotherapy arm compared to the placebo and chemotherapy arm in
KEYNOTE-407.
In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to
adverse reactions in 8% of 682 patients with metastatic NSCLC. The
most common adverse event resulting in permanent discontinuation of
KEYTRUDA was pneumonitis (1.8%). The most common adverse reactions
(≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%),
and nausea (20%).
In KEYNOTE-012, KEYTRUDA was discontinued due to adverse
reactions in 17% of 192 patients with HNSCC. Serious adverse
reactions occurred in 45% of patients. The most frequent serious
adverse reactions reported in at least 2% of patients were
pneumonia, dyspnea, confusional state, vomiting, pleural effusion,
and respiratory failure. The most common adverse reactions (≥20%)
were fatigue, decreased appetite, and dyspnea. Adverse reactions
occurring in patients with HNSCC were generally similar to those
occurring in patients with melanoma or NSCLC who received KEYTRUDA
as a monotherapy, with the exception of increased incidences of
facial edema and new or worsening hypothyroidism.
In KEYNOTE-087, KEYTRUDA was discontinued due to adverse
reactions in 5% of 210 patients with cHL. Serious adverse reactions
occurred in 16% of patients; those ≥1% included pneumonia,
pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two
patients died from causes other than disease progression; 1 from
GVHD after subsequent allogeneic HSCT and 1 from septic shock. The
most common adverse reactions (≥20%) were fatigue (26%), pyrexia
(24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and
rash (20%).
In KEYNOTE-170, KEYTRUDA was discontinued due to adverse
reactions in 8% of 53 patients with PMBCL. Serious adverse
reactions occurred in 26% of patients and included arrhythmia (4%),
cardiac tamponade (2%), myocardial infarction (2%), pericardial
effusion (2%), and pericarditis (2%). Six (11%) patients died
within 30 days of start of treatment. The most common adverse
reactions (≥20%) were musculoskeletal pain (30%), upper respiratory
tract infection and pyrexia (28% each), cough (26%), fatigue (23%),
and dyspnea (21%).
In KEYNOTE-052, KEYTRUDA was discontinued due to adverse
reactions in 11% of 370 patients with locally advanced or
metastatic urothelial carcinoma. Serious adverse reactions occurred
in 42% of patients; those ≥2% were urinary tract infection,
hematuria, acute kidney injury, pneumonia, and urosepsis. The most
common adverse reactions (≥20%) were fatigue (38%), musculoskeletal
pain (24%), decreased appetite (22%), constipation (21%), rash
(21%), and diarrhea (20%).
In KEYNOTE-045, KEYTRUDA was discontinued due to adverse
reactions in 8% of 266 patients with locally advanced or metastatic
urothelial carcinoma. The most common adverse reaction resulting in
permanent discontinuation of KEYTRUDA was pneumonitis (1.9%).
Serious adverse reactions occurred in 39% of KEYTRUDA-treated
patients; those ≥2% were urinary tract infection, pneumonia,
anemia, and pneumonitis. The most common adverse reactions (≥20%)
in patients who received KEYTRUDA were fatigue (38%),
musculoskeletal pain (32%), pruritus (23%), decreased appetite
(21%), nausea (21%), and rash (20%).
Adverse reactions occurring in patients with gastric cancer were
similar to those occurring in patients with melanoma or NSCLC who
received KEYTRUDA as a monotherapy.
In KEYNOTE-158, KEYTRUDA was discontinued due to adverse
reactions in 8% of 98 patients with recurrent or metastatic
cervical cancer. Serious adverse reactions occurred in 39% of
patients receiving KEYTRUDA; the most frequent included anemia
(7%), fistula, hemorrhage, and infections [except urinary tract
infections] (4.1% each). The most common adverse reactions (≥20%)
were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%),
pain and abdominal pain (22% each), and decreased appetite
(21%).
Adverse reactions occurring in patients with HCC were generally
similar to those in patients with melanoma or NSCLC who received
KEYTRUDA as a monotherapy, with the exception of increased
incidences of ascites (8% Grades 3-4) and immune-mediated hepatitis
(2.9%). Laboratory abnormalities (Grades 3-4) that occurred at a
higher incidence were elevated AST (20%), ALT (9%), and
hyperbilirubinemia (10%).
LactationIt is not known whether KEYTRUDA is excreted in
human milk. Because many drugs are excreted in human milk, instruct
women to discontinue nursing during treatment with KEYTRUDA and for
4 months after the final dose.
Pediatric UseThere is limited experience in pediatric
patients. In a study in 40 pediatric patients with advanced
melanoma, lymphoma, or PD-L1–positive advanced, relapsed, or
refractory solid tumors, the safety profile was similar to that
seen in adults treated with KEYTRUDA. Toxicities that occurred at a
higher rate (≥15% difference) in these patients when compared to
adults under 65 years of age were fatigue (45%), vomiting (38%),
abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia
(18%).
Merck’s Focus on CancerOur goal is to translate
breakthrough science into innovative oncology medicines to help
people with cancer worldwide. At Merck, the potential to bring new
hope to people with cancer drives our purpose and supporting
accessibility to our cancer medicines is our commitment. As part of
our focus on cancer, Merck is committed to exploring the potential
of immuno-oncology with one of the largest development programs in
the industry across more than 30 tumor types. We also continue to
strengthen our portfolio through strategic acquisitions and are
prioritizing the development of several promising oncology
candidates with the potential to improve the treatment of advanced
cancers. For more information about our oncology clinical trials,
visit www.merck.com/clinicaltrials.
About MerckFor more than a century, Merck, a leading
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The company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause
results to differ materially from those described in the
forward-looking statements can be found in the company’s 2017
Annual Report on Form 10-K and the company’s other filings with the
Securities and Exchange Commission (SEC) available at the SEC’s
Internet site (www.sec.gov).
Please see Prescribing Information for KEYTRUDA
at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and
Medication Guide for KEYTRUDA
at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf
View source
version on businesswire.com: https://www.businesswire.com/news/home/20181114005229/en/
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Investors:Teri Loxam(908) 740-1986
Michael DeCarbo908-740-1807
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