KEYTRUDA® (pembrolizumab) Demonstrated Improved Health-Related Quality of Life Compared to Chemotherapy in First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer (NSCLC)
December 7, 2016 2:45 am ET
First Presentation of Patient-Reported Outcomes from KEYNOTE-024 Study of Patients with Metastatic NSCLC Whose Tumors Have High PD-L1 Expression (Tumor Proportion Score [TPS] of 50 Percent or More)
Findings Presented in Plenary Session at 17 th World Conference on Lung Cancer
KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced positive health-related quality of life (HRQoL) findings
from an exploratory analysis from the phase 3 KEYNOTE-024 study
investigating the use of KEYTRUDA® (pembrolizumab), the
company’s anti-PD-1 therapy, compared to standard of care (SOC)
platinum-containing chemotherapy for the treatment of patients with
metastatic non-small cell lung cancer (NSCLC) whose tumors express high
levels of PD-L1 (tumor proportion score [TPS] of 50 percent or more).
Specifically, patient-reported outcomes showed clinically meaningful
improvement with KEYTRUDA compared to chemotherapy. Findings will be
presented today at the 17th World Conference on Lung Cancer
(WCLC) hosted by the International Association for the Study of Lung
Cancer.
“The patient-reported quality of life outcomes we are seeing in the
KEYNOTE-024 study are very encouraging and, coupled with previously
reported clinical data from this study, including a survival benefit,
are important in understanding the robust clinical profile for KEYTRUDA
compared to chemotherapy,” said Dr. Roger Dansey, senior vice president
and therapeutic area head, oncology late-stage development, Merck
Research Laboratories.
Dr. Julie Brahmer of the Johns Hopkins Kimmel Cancer Center will present
these findings as part of a plenary session at WCLC in Vienna, Austria
at 8:45 a.m. CET (Abstract #PL04a.01).
“For people living with lung cancer, who often face serious health
challenges brought on by the disease, quality of life is a major concern
when determining treatment and the data presented today help us further
understand the potential clinical benefit for KEYTRUDA in these
patients,” said Dr. Martin Reck, head of the thoracic oncology
department, LungenClinic Grosshansdorf, Germany.
The KEYTRUDA (pembrolizumab) clinical development program includes more
than 30 tumor types in nearly 400 clinical trials, including more than
200 trials that combine KEYTRUDA with other cancer treatments. Merck has
an expansive research program in NSCLC and is currently advancing
multiple registration-enabling studies with KEYTRUDA as monotherapy and
in combination with other treatments.
Findings from KEYNOTE-024
KEYNOTE-024 is a randomized, open-label, phase 3 study investigating
KEYTRUDA monotherapy compared to SOC platinum-containing chemotherapy
for the first-line treatment of patients with metastatic NSCLC. The
study enrolled 305 patients who had not received prior systemic
chemotherapy for their metastatic disease and whose tumors had high
PD-L1 expression (TPS of 50 percent or more) with no EGFR or ALK
aberrations. Patients were randomized to receive a 200 mg fixed dose of
KEYTRUDA every three weeks (n=154) or four to six cycles of
investigator’s choice platinum-based chemotherapy (n=151). The primary
outcome measure was progression-free survival. Key secondary outcomes
were overall survival, overall response rate and safety; exploratory
outcomes were duration of response and patient-reported outcomes.
The HRQoL data presented at WCLC were based on change from baseline to
week 15 as assessed by two European Organization for Research and
Treatment of Cancer (EORTC) Core Quality of Life Questionnaires
measuring global health status (such as physical, emotional, cognitive,
and social functioning as well as fatigue and pain) (QLQ-C30) and time
to deterioration (measuring symptoms such as cough, chest pain,
alopecia, and dyspnea) (QLQ-LC13). Across treatment arms,
patient-reported outcome compliance was greater than 90 percent at
baseline and approximately 80 percent at week 15.
The findings showed that HRQoL and symptoms were improved or maintained
to a greater degree with KEYTRUDA compared to chemotherapy (based on 299
patients who completed at least one questionnaire). Specifically, the
improvement in global health status from baseline to week 15 (difference
in least squares) for KEYTRUDA was 6.9 (95% CI, 3.3-10.6) compared to
-0.9 (95% CI, -4.8-3.0) in the chemotherapy arm. Analysis based on
specific functioning and symptoms showed more patients treated with
KEYTRUDA (pembrolizumab) reporting an improvement in global health
status and/or quality of life, fatigue, and pain compared to patients
treated with chemotherapy. Fewer patients in the KEYTRUDA arm
experienced deterioration compared to chemotherapy (30.5% and 39.2%,
respectively), with a prolonged time to deterioration also observed in
the KEYTRUDA arm (hazard ratio: 0.66 [95% CI, 0.44-0.97; p=0.029]).
About KEYTRUDA
®
(pembrolizumab)
KEYTRUDA is a humanized monoclonal antibody that works by increasing the
ability of the body’s immune system to help detect and fight tumor
cells. KEYTRUDA 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.
KEYTRUDA is administered as an intravenous infusion over 30 minutes
every three weeks for the approved indications. KEYTRUDA for injection
is supplied in a 100 mg single use vial.
KEYTRUDA Indications and Dosing
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma at a dose of 2 mg/kg every three weeks until disease
progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA 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 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.
In metastatic NSCLC, KEYTRUDA (pembrolizumab) 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.
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.
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 (pembrolizumab) for Grade 2; withhold or
discontinue for Grade 3 or 4 hypophysitis.
KEYTRUDA 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. 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
KEYTRUDA can cause other clinically important immune-mediated adverse
reactions. 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%), exfoliative dermatitis, bullous pemphigoid, rash
(1.4%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis,
vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising
in a patient with inflammatory foci in brain parenchyma.
KEYTRUDA can cause severe or life-threatening infusion-related
reactions, 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.
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.
KEYTRUDA 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%).
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.
Safety and effectiveness of KEYTRUDA have not been established in
pediatric patients.
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 that includes nearly 400 clinical trials 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 125 years, Merck has been a global health care leader working to
help the world be well. Merck is known as MSD outside the United States
and Canada. 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.
For more information, visit www.merck.com
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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
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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
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including obtaining regulatory approval; the company’s ability to
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and other protections for innovative products; and the exposure to
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The company undertakes no obligation to publicly update any
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to differ materially from those described in the forward-looking
statements can be found in the company’s 2015 Annual Report on Form 10-K
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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
.
Merck
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