Updated Data from Phase 3 KEYNOTE-045 Trial
to Be Presented at ESMO 2017 Congress
Merck (NYSE: MRK), known as MSD outside the United States and
Canada, today announced updated results from the phase 3
KEYNOTE-045 trial evaluating KEYTRUDA® (pembrolizumab), the
company’s anti-PD-1 therapy, in patients with locally advanced or
metastatic urothelial carcinoma (a type of bladder cancer) with
disease progression on or after platinum-containing chemotherapy
(post-platinum failure). Updated data show that with median
follow-up of 22.5 months, KEYTRUDA continues to demonstrate an
overall survival (OS) benefit over investigator’s choice of
paclitaxel, docetaxel or vinflunine as a second-line therapy,
post-platinum failure, regardless of PD-L1 expression (HR, 0.70
[95% CI, 0.57-0.86], p=0.0003). Findings are being presented at the
European Society for Medical Oncology (ESMO) 2017 Congress in
Madrid, Spain, on Sunday, Sept. 10 (poster from 2:45 – 4:15 p.m.
CEST; discussion: 3:15 – 3:45 p.m. CEST) (Location: Cordoba
Auditorium) (Abstract #LBA37_PR).
“These data at ESMO provide further insights and greater
understanding in using KEYTRUDA in select second-line advanced
urothelial carcinoma treatment settings, and importantly,
demonstrate an overall survival advantage with KEYTRUDA compared to
standard chemotherapy agents vinflunine, docetaxel and paclitaxel,
which are common in clinical practice for the treatment of this
disease,” said professor Ronald de Wit, M.D., Ph.D., group leader
experimental systemic therapy of urogenital cancers, Erasmus MC
Cancer Institute. “For previously treated patients, post-platinum
failure, these findings are also encouraging as they show an
overall survival benefit regardless of PD-L1 status or choice of
commonly used chemotherapy.”
“With nearly two years follow-up, these updated phase 3 data
continue to show an overall survival benefit with KEYTRUDA in
patients with advanced urothelial carcinoma whose cancer has
progressed after receiving previous treatment for their disease,”
said Dr. Roger Dansey, senior vice president and therapeutic area
head, oncology late-stage development, Merck Research Laboratories.
“We are pleased that, with the approval in the U.S. and recent
approval of KEYTRUDA in the EU, more patients now have an important
treatment option available to them.”
Currently, Merck also has the largest immuno-oncology clinical
development program in bladder cancer, with 29 trials underway
involving KEYTRUDA (pembrolizumab) as monotherapy and in
combination, including four registration-enabling studies.
Data in Second-Line Post-Platinum Failure Patients,
KEYNOTE-045
KEYNOTE-045 is an open-label, randomized phase 3 trial of
KEYTRUDA compared to investigator’s choice of chemotherapy
(paclitaxel, docetaxel or vinflunine) in patients with locally
advanced or metastatic urothelial cancer with disease progression
on or after platinum-containing chemotherapy. The trial was
prematurely stopped after a pre-planned interim analysis
demonstrated significantly longer OS with KEYTRUDA compared to
chemotherapy (median follow-up, 14.1 months). Efficacy was assessed
in the overall study population (n=542), as well as in patients
with PD-L1 expression – defined as a combined positive score of 10
or more (CPS ≥10) (KEYTRUDA arm: n=74/270; chemotherapy arm;
n=90/272) (additional details on the trial design are provided
below).
Data presented at ESMO (Abstract #LBA37_PR) include four months
of additional follow-up (data cut-off, May 19, 2017; median follow
up, 22.5 months) and continue to show a superior OS advantage with
KEYTRUDA compared to chemotherapy in the second-line setting,
regardless of PD-L1 expression. In the overall study population,
data show a 30 percent reduction in the risk of death with KEYTRUDA
(HR, 0.70 [95% CI, 0.57-0.86], p=0.0003), the median OS was 10.3
months with KEYTRUDA (95% CI, 8.0-12.3) and 7.4 months with
chemotherapy (95% CI, 6.3-8.3), and the 18-month OS rate was 33.2
percent with KEYTRUDA compared to 19.7 percent with chemotherapy.
Analysis of OS based on PD-L1 expression show a 42 percent
reduction in the risk of death with KEYTRUDA (HR, 0.58 [95% CI,
0.39-0.86], p=0.0029) in patients whose tumors expressed PD-L1 (CPS
≥10), the median OS was 8.0 months with KEYTRUDA (95% CI, 5.0-12.3)
and 5.2 months with chemotherapy (95% CI, 4.2-7.5), and the
18-month OS rate was 30.0 percent with KEYTRUDA compared to 16.9
percent with chemotherapy.
As previously reported, there was no significant difference in
progression-free-survival (PFS) between treatment arms in the
overall study population (HR, 0.96 [95% CI, 0.79-1.16], p=0.32).
The median PFS was 2.1 months with KEYTRUDA (95% CI, 2.0-2.2) and
3.3 months with chemotherapy (95% CI, 2.4-3.5); the 18-month PFS
rate was 15.3 percent with KEYTRUDA (pembrolizumab) compared to 4.8
percent with chemotherapy. In patients whose tumors expressed PD-L1
(CPS ≥10), the median PFS was 2.1 months with KEYTRUDA (95% CI,
1.9-2.1) and 3.2 months with chemotherapy (95% CI, 2.2-3.5); the
18-month PFS rate was 16.3 percent with KEYTRUDA compared to 5.3
percent with chemotherapy (HR, 0.93 [95% CI, 0.65-1.33],
p=0.32).
Analyses of the secondary endpoints showed nearly double the
overall response rate (ORR) with KEYTRUDA compared to chemotherapy
in the overall study population, with an ORR of 21.1 percent in the
KEYTRUDA arm (complete response rate (CR) of 7.8 percent and a
partial response rate (PR) of 13.3 percent) and 11.0 percent in the
chemotherapy arm (CR of 2.9 percent and a PR of 8.1 percent). The
median time to response was 2.1 months in both treatment arms; 57.9
percent of responses in the KEYTRUDA arm were ongoing at the time
of analysis compared to 20.0 percent in the chemotherapy arm.
Median duration of response in patients with partial or complete
responses had not yet been reached in the KEYTRUDA arm at the time
of analysis (range: 1.6+ to 24.6+) with 67.0 percent of responses
ongoing at 12 months (calculated per Kaplan-Meier curve); in the
chemotherapy arm, the median duration of response was 4.4 months
(range: 1.4+ to 24.0+) with 35.0 percent of responses ongoing at 12
months (calculated per Kaplan-Meier curve).
In patients whose tumors expressed PD-L1, the ORR was 20.3
percent in the KEYTRUDA arm (CR of 6.8 percent and a PR of 13.5
percent) and 6.7 percent in the chemotherapy arm (CR of 2.2 percent
and a PR of 4.4 percent). The median time to response was 2.0
months in the KEYTRUDA arm and 2.1 months in the chemotherapy arm;
73.3 percent of responses in the KEYTRUDA arm were ongoing at the
time of analysis compared to 33.3 percent in the chemotherapy arm.
The median duration of response in patients with partial or
complete responses had not yet been reached in the KEYTRUDA arm at
the time of analysis (range: 1.6+ to 23.5+) with 77.0 percent of
responses ongoing at 12 months (calculated per Kaplan-Meier curve);
in the chemotherapy arm, the median duration of response was 4.4
months (range: 1.5+ to 20.8+) with 40.0 percent of responses
ongoing at 12 months (calculated per Kaplan-Meier curve).
A second abstract including a subgroup analysis from KEYNOTE-045
(Abstract #851PD) was also accepted as a poster at ESMO and
provides greater insight into the OS advantage with KEYTRUDA
compared to the individual chemotherapy agents. The retrospective
analysis showed a 27 percent reduction in the risk of death versus
paclitaxel (HR, 0.73 [95% CI, 0.55-0.96]), a 21 percent reduction
in the risk of death versus docetaxel (HR, 0.79 [95% CI,
0.59-1.07]), and a 35 percent reduction in the risk of death versus
vinflunine (HR, 0.65 [95% CI, 0.49-0.87]). No statistically
significant difference in PFS was seen between KEYTRUDA and each
chemotherapy agent. Analyses of the secondary endpoints showed an
ORR of 11.9 percent, 6.0 percent, and 17.2 percent with paclitaxel,
docetaxel, and vinflunine, respectively, compared to 21.1 percent
in the KEYTRUDA (pembrolizumab) arm.
The safety profile of KEYTRUDA was consistent with that observed
in previously reported studies. Treatment-related adverse events
(TRAEs) of any grade occurred in 62.0 percent in the KEYTRUDA arm
and 90.6 percent in the chemotherapy arm. Grade 3 or higher TRAEs
occurred in 16.5 percent and 50.2 percent of KEYTRUDA and
chemotherapy patients, respectively. Immune-mediated adverse events
occurred in 19.5 percent of patients in the KEYTRUDA arm and 7.5
percent in the chemotherapy arm. The discontinuation rate due to
treatment-related adverse events was 7.1 percent of patients in the
KEYTRUDA arm and 12.5 percent of patients in the chemotherapy arm.
Deaths due to treatment-related adverse events occurred in four
patients treated with KEYTRUDA, one patient treated with
paclitaxel, and three patients treated with vinflunine.
About KEYNOTE-045
In KEYNOTE-045, patients were randomized to receive either
KEYTRUDA 200 mg every three weeks (n=270) or investigator’s choice
of any of the following chemotherapy regimens, all given
intravenously, every three weeks (n=272): paclitaxel 175 mg/m2,
docetaxel 75 mg/m2, or vinflunine 320 mg/m2. The dual primary
endpoints were OS and PFS, as assessed by blinded independent
central review (BICR) per RECIST (Response Evaluation Criteria in
Solid Tumors) v1.1; key secondary endpoints included ORR, as
assessed by BICR per RECIST 1.1, duration of response and safety.
Efficacy was assessed in all patients, as well as in patients with
PD-L1 expression.
About KEYTRUDA® (pembrolizumab) Injection
100mg
KEYTRUDA 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.
Studies of KEYTRUDA – from the largest immuno-oncology program
in the industry with more than 550 trials – include a wide variety
of cancers and treatment settings. The KEYTRUDA clinical program
seeks to understand factors that predict a patient’s likelihood of
benefitting from treatment with KEYTRUDA, including the exploration
of several different biomarkers across a broad range of tumors.
KEYTRUDA (pembrolizumab) Indications and
Dosing
Melanoma
KEYTRUDA 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 Cancer
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 also 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.
KEYTRUDA, in combination with pemetrexed and carboplatin, is
indicated for the first-line treatment of patients with metastatic
nonsquamous NSCLC. This indication is approved under accelerated
approval based on tumor response rate and progression-free
survival. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials.
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 pemetrexed
and carboplatin.
Head and Neck Cancer
KEYTRUDA 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 Lymphoma
KEYTRUDA (pembrolizumab) is indicated for the treatment of adult
and pediatric patients with refractory classical Hodgkin lymphoma
(cHL), or who have relapsed after three 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.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma who are not eligible
for cisplatin-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
the confirmatory trials.
KEYTRUDA is also indicated for the treatment of patients with
locally advanced or metastatic urothelial carcinoma 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) Cancer
KEYTRUDA 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 (pembrolizumab) 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 pediatric patients 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.
Selected Important Safety Information for
KEYTRUDA® (pembrolizumab)
KEYTRUDA can cause immune-mediated pneumonitis, including fatal
cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients receiving
KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%),
and 5 (0.1%) pneumonitis, 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.
KEYTRUDA can cause immune-mediated colitis. Colitis occurred in
48 (1.7%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.4%), 3 (1.1%), and 4 (<0.1%) colitis. 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.
KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred
in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.1%), 3 (0.4%), and 4 (<0.1%) hepatitis. 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.
KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17
(0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. Monitor patients
for signs and symptoms of hypophysitis (including hypopituitarism
and adrenal insufficiency). Administer corticosteroids and hormone
replacement as clinically indicated. Withhold KEYTRUDA for Grade 2;
withhold or discontinue for Grade 3 or 4 hypophysitis.
KEYTRUDA (pembrolizumab) can cause thyroid disorders, including
hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism
occurred in 96 (3.4%) of 2799 patients receiving KEYTRUDA,
including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism.
Hypothyroidism occurred in 237 (8.5%) of 2799 patients receiving
KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The
incidence of new or worsening hypothyroidism was higher in patients
with HNSCC, occurring in 28 (15%) of 192 patients with HNSCC,
including Grade 3 (0.5%) hypothyroidism. Thyroiditis occurred in 16
(0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.3%) thyroiditis. Monitor patients for changes in thyroid
function (at the start of treatment, periodically during treatment,
and as indicated based on clinical evaluation) and for clinical
signs and symptoms of thyroid disorders. Administer replacement
hormones for hypothyroidism and manage hyperthyroidism with
thionamides and beta-blockers as appropriate. Withhold or
discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.
KEYTRUDA can cause type 1 diabetes mellitus, including diabetic
ketoacidosis, which have been reported in 6 (0.2%) of 2799
patients. Monitor patients for hyperglycemia or other signs and
symptoms of diabetes. Administer insulin for type 1 diabetes, and
withhold KEYTRUDA and administer antihyperglycemics in patients
with severe hyperglycemia.
KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred
in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for
changes in renal function. Administer corticosteroids for Grade 2
or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently
discontinue KEYTRUDA for Grade 3 or 4 nephritis.
Immune-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 and
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.
KEYTRUDA can cause other clinically important immune-mediated
adverse reactions. These immune-mediated reactions may occur in any
organ system. 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
(pembrolizumab) 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, and partial seizures arising in a patient with inflammatory
foci in brain parenchyma. In addition, myelitis and myocarditis
were reported in other clinical trials, including classical Hodgkin
lymphoma, and postmarketing use.
Solid organ transplant rejection has been reported in
postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase
the risk of rejection in solid organ transplant recipients.
Consider the benefit of treatment with KEYTRUDA vs the risk of
possible organ rejection in these patients.
KEYTRUDA can cause severe or life-threatening infusion-related
reactions, including hypersensitivity and anaphylaxis, which have
been reported in 6 (0.2%) of 2799 patients. Monitor patients for
signs and symptoms of infusion-related reactions, including rigors,
chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia,
and fever. For Grade 3 or 4 reactions, stop infusion and
permanently discontinue KEYTRUDA.
Immune-mediated complications, including fatal events, occurred
in patients who underwent allogeneic hematopoietic stem cell
transplantation (HSCT) after being treated with KEYTRUDA. Of 23
patients with cHL who proceeded to allogeneic HSCT after treatment
with KEYTRUDA on any trial, 6 patients (26%) developed
graft-versus-host-disease (GVHD), one of which was fatal, and 2
patients (9%) developed severe hepatic veno-occlusive disease (VOD)
after reduced-intensity conditioning, one of which was fatal. 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. 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.
Based 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.
In KEYNOTE-006, KEYTRUDA was discontinued due to adverse
reactions in 9% of 555 patients with advanced melanoma; adverse
reactions leading to 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%). Adverse
reactions leading to interruption of KEYTRUDA (pembrolizumab)
occurred in 21% of patients; the most common (≥1%) was diarrhea
(2.5%). The most common adverse reactions with KEYTRUDA vs
ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA),
rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding
incidence rates are listed for ipilimumab only for those adverse
reactions that occurred at the same or lower rate than with
KEYTRUDA.
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%). Adverse reactions leading to interruption
of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were
diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme
elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%).
The most common adverse reactions (occurring in at least 20% of
patients and at a higher incidence than with docetaxel) were
decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea
(20% vs 18%).
When KEYTRUDA was administered in combination with carboplatin
and pemetrexed (carbo/pem), KEYTRUDA was discontinued in 10% of 59
patients. The most common adverse reaction resulting in
discontinuation of KEYTRUDA (≥2%) was acute kidney injury (3.4%).
Adverse reactions leading to interruption of KEYTRUDA occurred in
39% of patients; the most common (≥2%) were fatigue (8%),
neutrophil count decreased (8%), anemia (5%), dyspnea (3.4%), and
pneumonitis (3.4%).The most common adverse reactions (≥20%) with
KEYTRUDA compared to carbo/pem alone were fatigue (71% vs 50%),
nausea (68% vs 56%), constipation (51% vs 37%), rash (42% vs 21%),
vomiting (39% vs 27%), dyspnea (39% vs 21%), diarrhea (37% vs 23%),
decreased appetite (31% vs 23%), headache (31% vs 16%), cough (24%
vs 18%), dizziness (24% vs 16%), insomnia (24% vs 15%), pruritus
(24% vs 4.8%), peripheral edema (22% vs 18%), dysgeusia (20% vs
11%), alopecia (20% vs 3.2%), upper respiratory tract infection
(20% vs 3.2%), and arthralgia (15% vs 24%). This study was not
designed to demonstrate a statistically significant difference in
adverse reaction rates for KEYTRUDA as compared to carbo/pem alone
for any specified adverse reaction.
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 (reported in at least 20% of patients)
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, with the exception of
increased incidences of facial edema (10% all Grades; 2.1% Grades 3
or 4) and new or worsening hypothyroidism.
KEYTRUDA (pembrolizumab) was discontinued due to adverse
reactions in 5% of 210 patients with cHL, and treatment was
interrupted due to adverse reactions in 26% of patients. Fifteen
percent (15%) of patients had an adverse reaction requiring
systemic corticosteroid therapy. Serious adverse reactions occurred
in 16% of patients. The most frequent serious adverse reactions
(≥1%) included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and
herpes zoster. Two patients died from causes other than disease
progression; one from GVHD after subsequent allogeneic HSCT and one
from septic shock. The most common adverse reactions (occurring in
≥20% of patients) were fatigue (26%), pyrexia (24%), cough (24%),
musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
In KEYNOTE-052, KEYTRUDA was discontinued due to adverse
reactions in 11% of 370 patients with locally advanced or
metastatic urothelial carcinoma. The most common adverse reactions
(in≥20% of patients) were fatigue (38%), musculoskeletal pain
(24%), decreased appetite (22%), constipation (21%), rash (21%),
and diarrhea (20%). Eighteen patients (5%) died from causes other
than disease progression. Five patients (1.4%) who were treated
with KEYTRUDA experienced sepsis which led to death, and 3 patients
(0.8%) experienced pneumonia which led to death. Adverse reactions
leading to interruption of KEYTRUDA occurred in 22% of patients;
the most common (≥1%) were liver enzyme increase, diarrhea, urinary
tract infection, acute kidney injury, fatigue, joint pain, and
pneumonia. Serious adverse reactions occurred in 42% of patients,
the most frequent (≥2%) of which were urinary tract infection,
hematuria, acute kidney injury, pneumonia, and urosepsis.
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%).
Adverse reactions leading to interruption of KEYTRUDA occurred in
20% of patients; the most common (≥1%) were urinary tract infection
(1.5%), diarrhea (1.5%), and colitis (1.1%). The most common
adverse reactions (20%) in patients who received KEYTRUDA vs those
who received chemotherapy were fatigue (38% vs 56%),
musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%), decreased
appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs 13%).
Serious adverse reactions occurred in 39% of KEYTRUDA-treated
patients, the most frequent (≥2%) of which were urinary tract
infection, pneumonia, anemia, and pneumonitis.
There is limited experience in pediatric patients. Efficacy for
pediatric patients was extrapolated from the results in the adult
cHL population. In a study of 40 pediatric patients with advanced
melanoma, PD-L1–positive advanced, relapsed, or refractory solid
tumors or lymphoma, patients were treated with KEYTRUDA
(pembrolizumab) for a median of 43 days (range 1-414 days), with 24
patients (60%) receiving treatment for 42 days or more. The safety
profile in pediatric patients 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%).
It 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.
Our Focus on Cancer
Our goal is to translate breakthrough science into innovative
oncology medicines to help people with cancer worldwide. At Merck,
helping people fight cancer is our passion and supporting
accessibility to our cancer medicines is our commitment. Our focus
is on pursuing research in immuno-oncology and we are accelerating
every step in the journey – from lab to clinic – to potentially
bring new hope to people with cancer.
As part of our focus on cancer, Merck is committed to exploring
the potential of immuno-oncology with one of the fastest-growing
development programs in the industry. We are currently executing an
expansive research program evaluating our anti-PD-1 therapy across
more than 30 tumor types. We also continue to strengthen our
immuno-oncology portfolio through strategic acquisitions and are
prioritizing the development of several promising immunotherapeutic
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 Merck
For more than a century, Merck, a leading global
biopharmaceutical company known as MSD outside of the United States
and Canada, has been inventing for life, bringing forward medicines
and vaccines for many of the world’s most challenging diseases.
Through our prescription medicines, vaccines, biologic therapies
and animal health products, we work with customers and operate in
more than 140 countries to deliver innovative health solutions. We
also demonstrate our commitment to increasing access to health care
through far-reaching policies, programs and partnerships. Today,
Merck continues to be at the forefront of research to advance the
prevention and treatment of diseases that threaten people and
communities around the world - including cancer, cardio-metabolic
diseases, emerging animal diseases, Alzheimer’s disease and
infectious diseases including HIV and Ebola. For more information,
visit www.merck.com and connect with us
on Twitter, Facebook, Instagram, YouTube
and LinkedIn.
Forward-Looking Statement of Merck & Co., Inc.,
Kenilworth, N.J., USA
This news release of Merck & Co., Inc., Kenilworth, N.J.,
USA (the “company”) includes “forward-looking statements” within
the meaning of the safe harbor provisions of the U.S. Private
Securities Litigation Reform Act of 1995. These statements are
based upon the current beliefs and expectations of the company’s
management and are subject to significant risks and uncertainties.
There can be no guarantees with respect to pipeline products that
the products will receive the necessary regulatory approvals or
that they will prove to be commercially successful. If underlying
assumptions prove inaccurate or risks or uncertainties materialize,
actual results may differ materially from those set forth in the
forward-looking statements.
Risks and uncertainties include but are not limited to, general
industry conditions and competition; general economic factors,
including interest rate and currency exchange rate fluctuations;
the impact of pharmaceutical industry regulation and health care
legislation in the United States and internationally; global trends
toward health care cost containment; technological advances, new
products and patents attained by competitors; challenges inherent
in new product development, including obtaining regulatory
approval; the company’s ability to accurately predict future market
conditions; manufacturing difficulties or delays; financial
instability of international economies and sovereign risk;
dependence on the effectiveness of the company’s patents and other
protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory
actions.
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 2016
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
(pembrolizumab)
at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and
Patient Information/Medication Guide for KEYTRUDA
at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20170910005046/en/
MerckMedia:Pamela Eisele, 267-305-3558orCourtney Ronaldo,
908-740-6132orInvestorsTeri Loxam, 908-740-1986orAmy Klug,
908-740-1898
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