ASH Clinical News April 2016 | Page 64
Care Path of Least Resistance
images should be obtained and when, what laboratory
values are needed, the preferred initial treatment plan,
which drug regimen to use and how often, and what
surveillance strategy should be used. Critical to this process is identifying the evidence that supports these decisions. Care paths can be developed at an institutional
level, or by a committee of experts at a medical society
or national level, ideally using standardized methodology in identifying preferred treatment strategies in the
absence of any conflict of interest.
“There are many ways to treat cancers – more than
ever – and by coming up with a
common approach, there is a simple
reduction in variability that reduces
people ordering whatever they want,
whenever they want, without the
data to back up those decisions,” Dr.
Bolwell said. “Things get standardized and fewer resources are
consumed.”
At Cleveland Clinic, Dr. Bolwell
said that multidisciplinary teams
meet several times a year to keep
these care paths current, incorporating the newest technology or drugs.
They also embed quality metrics
into the paths to track their use and
efficacy.
“For example, for some cancers
treated by surgery, the number of
lymph nodes sampled is a quality metric,” he explained. “Or for
B-cell lymphoma, a quality metric
might measure whether or not the
patient got a pretreatment PET
scan.” By tracking these metrics,
the institution can track adherence
to a pathway and identify areas for
improvement.
Increased Value
According to Dr. Longworth, data
that back up the idea that clinical
care paths provide value and save
resources are only beginning to
emerge. Most of the evidence at this
point is anecdotal.
At the 2014 ASH Annual Meeting, Dr. Bolwell and colleague s
presented early data from a study
conducted at Cleveland Clinic about
the care path for upfront treatment
of patients with myeloma, finding
that most patients achieved uniform
disease control using fewer drugs
than the standard approach.1
In the pathway, patients with
multiple myeloma were started on
a two-drug regimen (lenalidomide
and dexamethasone) as opposed to
a three-drug regimen (bortezomib,
lenalidomide, and dexamethasone),
both of which may be considered standards of care. Care-path
developers selected the two-drug
regimen to avoid the higher risk for
side effects (including peripheral
neuropathy), and higher costs associated with the three-drug regimen,
without a clear-cut improvement in
overall survival. If patients did not
have at least a minimal response (<50% decrease in M
protein) after the first treatment cycle, or at least partial
response (>50% decrease in M protein) after the second
cycle, treatment could be adapted with sequential addition of agents.
After 15 months of implementation, the 24 patients
who were treated following the care path achieved
minimal response or better, with 60 percent of patients
requiring treatment with only two drugs. “Overall
survival will be the ultimate assessment of the utility of
this approach, but response assessments to date support
ongoing utilization of the care path,” the authors wrote.
In addition, compared with standard use of the threedrug regimen, an adapted approach reduced the risk of
peripheral neuropathy and lowered costs, with a savings
in drug costs alone of more than $4,000 per treatment
cycle.
More recently, at the 2015 American Society of
Clinical Oncology (ASCO) Annual Meeting, Cleveland
Clinic researchers presented data from an evaluation
of a clinical care path’s effect on treatment decisions
and health-care costs for non-small cell lung cancer.2 In
INDICATION AND IMPORTANT SAFETY INFORMATION
INDICATION
KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with
relapsed or refractory multiple myeloma who have received one to three lines of therapy.
IMPORTANT SAFETY INFORMATION
Cardiac Toxicities: New onset or worsening of pre-existing cardiac
failure (e.g., congestive heart failure, pulmonary edema, decreased
ejection fraction), restrictive cardiomyopathy, myocardial ischemia,
and myocardial infarction including fatalities have occurred following
administration of KYPROLIS. Some events occurred in patients with
normal baseline ventricular function. Death due to cardiac arrest has
occurred within one day of KYPROLIS administration.
• Monitor patients for clinical signs or symptoms of cardiac failure or
cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected.
Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until
recovery, and consider whether to restart KYPROLIS at 1 dose level
reduction based on a benefit/risk assessment.
• While adequate hydration is required prior to each dose in Cycle 1,
monitor all patients for evidence of volume overload, especially
patients at risk for cardiac failure. Adjust total fluid intake as clinically
appropriate in patients with baseline cardiac failure or who are at risk
for cardiac failure.
• Patients ≥ 75 years, the risk of cardiac failure is increased. Patients
with New York Heart Association Class III and IV heart failure,
recent myocardial infarction, conduction abnormalities, angina, or
arrhythmias may be at greater risk for cardiac complications and
should have a comprehensive medical assessment (including blood
pressure and fluid management) prior to starting treatment with
KYPROLIS and remain under close follow-up.
Acute Renal Failure: Cases of acute renal failure and renal insufficiency
adverse events (including renal failure) have occurred in patients
receiving KYPROLIS. Acute renal failure was reported more frequently in
patients with advanced relapsed and refractory multiple myeloma who
received KYPROLIS monotherapy. Monitor renal function with regular
measurement of the serum creatinine and/or estimated creatinine
clearance. Reduce or withhold dose as appropriate.
Tumor Lysis Syndrome: Cases of Tumor Lysis Syndrome (TLS),
including fatal outcomes, have occurred in patients receiving KYPROLIS.
Patients with multiple myeloma and a high tumor burden should be
considered at greater risk for TLS. Adequate hydration is required prior
to each dose in Cycle 1, and in subsequent cycles as needed. Consider
uric acid lowering drugs in patients at risk for TLS. Monitor for evidence
of TLS during treatment and manage promptly. Withhold KYPROLIS until
TLS is resolved.
Pulmonary Toxicity: Acute Respiratory Distress Syndrome (ARDS),
acute respiratory failure, and acute diffuse infiltrative pulmonary disease
such as pneumonitis and interstitial lung disease have occurred in
patients receiving KYPROLIS. Some events have been fatal. In the event
of drug-induced pulmonary toxicity, discontinue KYPROLIS.
Pulmonary Hypertension: Pulmonary arterial hypertension (PAH)
was reported in patients treated with KYPROLIS. Evaluate with cardiac
imaging and/or other tests as indicated. Withhold KYPROLIS for PAH
until resolved or returned to baseline and consider whether to restart
KYPROLIS based on a benefit/risk assessment.
Dyspnea: Dyspnea was reported in patients treated with KYPROLIS.
Evaluate dyspnea to exclude cardiopulmonary conditions including
cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3 or
4 dyspnea until resolved or returned to baseline. Consider whether
to restart KYPROLIS based on a benefit/risk assessment.
Hypertension: Hypertension, including hypertensive crisis and
hypertensive emergency, has been observed with KYPROLIS. Some
of these events have been fatal. Monitor blood pressure regularly in
all patients. If hypertension cannot be adequately controlled, withhold
KYPROLIS and evaluate. Consider whether to restart KYPROLIS based
on a benefit/risk assessment.
Venous Thrombosis: Venous thromboembolic events (including deep
venous thrombosis and pulmonary embolism) have bee n observed with
KYPROLIS. Thromboprophylaxis is recommended for patients being
treated with the combination of KYPROLIS with dexamethasone or with
lenalidomide plus dexamethasone. The thromboprophylaxis regimen
should be based on an assessment of the patient’s underlying risks.
• Patients using oral contraceptives or a hormonal method of contraception
associated with a risk of thrombosis should consider an alternative
method of effective contraception during treatment with KYPROLIS in
combination with dexamethasone or lenalidomide plus dexamethasone.
Infusion Reactions: Infusion reactions, including life-threatening
reactions, have occurred in patients receiving KYPROLIS. Symptoms
include fever, chills, arthralgia, myalgia, facial flushing, facial edema,
vomiting, weakness, shortness of breath, hypotension, syncope, chest
tightness, or angina. These reactions can occur immediately following
or up to 24 hours after administration of KYPROLIS. Premedicate
with dexamethasone to reduce the incidence and severity of infusion
reactions. Inform patients of the risk and of symptoms of an infusion
reaction and to contact a physician immediately if they occur.
Thrombocytopenia: KYPROLIS causes thrombocytopenia with
recovery to baseline platelet count usually by the start of the next
cycle. Thrombocytopenia was reported in patients receiving KYPROLIS.
Monitor platelet counts frequently during treatment with KYPROLIS.
Reduce or withhold dose as appropriate.
Hepatic Toxicity and Hepatic Failure: Cases of hepatic failure,
including fatal cases, have been reported during treatment with
KYPROLIS. KYPROLIS can cause increased serum transaminases.
Monitor liver enzymes regularly regardless of baseline values.
Reduce or withhold dose as appropriate.
Thrombotic Microangiopathy: Cases of thrombotic microangiopathy,
including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
(TTP/HUS), including fatal outcome have occurred in patients receiving
KYPROLIS. Monitor for signs and symptoms of TTP/HUS. Discontinue
KYPROLIS if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded,
KYPROLIS may be restarted. The safety of reinitiating KYPROLIS therapy
in patients previously experiencing TTP/HUS is not known.
Posterior Reversible Encephalopathy Syndrome (PRES): Cases of
PRES have occurred in patients receiving KYPROLIS. PRES was formerly
known as Reversible Posterior Leukoencephalopathy Syndrome.
Consider a neuro-radiological imaging (MRI) for onset of visual or
neurological symptoms. Discontinue KYPROLIS if PRES is suspected
and evaluate. The safety of reinitiating KYPROLIS therapy in patients
previously experiencing PRES is not known.
Embryo-fetal Toxicity: KYPROLIS can cause fetal harm when
administered to a pregnant woman based on its mechanism of action
and findings in animals.
• Females of reproductive potential should be advised to avoid becoming
pregnant while being treated with KYPROLIS. Males of reproductive
potential should be advised to avoid fathering a child while being
treated with KYPROLIS. If this drug is used during pregnancy, or
if pregnancy occurs while taking this drug, the patient should be
apprised of the potential hazard to the fetus.
ADVERSE REACTIONS
• The most common adverse reactions occurring in at least 20% of
patients treated with KYPROLIS in the combination therapy trials:
anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia,
pyrexia, insomnia, muscle spasm, cough, upper respiratory tract
infection, hypokalemia.
You are encouraged to report negative side effects of prescription
drugs to the FDA. Visit MedWatch or call 1-800-FDA-1088.
Please see Brief Summary of full Prescribing Information on adjacent pages.
©2016 Onyx Pharmaceuticals, Inc., an Amgen Inc. subsidiary, Thousand Oaks, CA USA-171-120752 February 2016 Printed in USA
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ASH Clinical News