WebMD Help
delivers an efficient and accountable digital media + direct relationship management platform with the unique ability to enable hospitals to build physician practices, grow admissions, differentiate their brands, and improve the health of their populations.
Sunday, December 6, 2015
Takeda Reports Five-Year Overall Survival Data for ADCETRIS® (Brentuximab Vedotin) Demonstrate Durable Remissions in Relapsed/Refractory Hodgkin Lymphoma
ORLANDO, Fla.--(BUSINESS WIRE)--Takeda Pharmaceutical Company Limited (TSE:4502)
announced post-treatment follow up data from the pivotal phase 2 study
of single-agent brentuximab vedotin for the treatment of relapsed or
refractory Hodgkin lymphoma following autologous stem cell
transplantation (ASCT). Lamisil (Terbinafine) with free prescription The data demonstrated that the estimated
five-year overall survival (OS) rate among ADCETRIS-treated patients was
41 percent (95% CI: 31%, 51%); median OS was 40.5 months (95% CI: 28.7,
61.9 [range 1.8 to 72.9+]) and median progression-free survival (PFS)
was 9.3 months (95% CI: 7.1 to 12.2 months). Mobic (Meloxicam) with no prescription The safety profile of
ADCETRIS was generally consistent with the existing prescribing
information. Buy Ashwafera () with free Rx These results were presented today at the 57th
American Society of Hematology (ASH) annual meeting in Orlando, FL.
“The five year overall survival rates reported in this pivotal trial are
very promising in improving the long-term outlook for patients in this
setting as outcomes have historically been very poor,” said Professor
Andreas Engert, M.D., University Hospital of Cologne, Germany. Buy Invagesic without Rx “These
data further reinforce the emergence of ADCETRIS as a standard of care
for patients with Hodgkin lymphoma who experience relapse or disease
progression following salvage therapy and ASCT.”
Also presented today at the ASH annual meeting, data from the phase 3
AETHERA trial of brentuximab vedotin consolidation therapy in Hodgkin
lymphoma patients at high risk of relapse following ACST demonstrated
that after three years of follow-up, patients treated with brentuximab
vedotin continued to show a significant improvement in PFS per
investigator assessment (61%; 95% CI:53%, 68% HR 0.52) compared to
placebo (43%; 95% CI:36%, 51% HR 0.52). Buy Capoten (Captopril) with no Rx The safety profile of ADCETRIS
was generally consistent with the existing prescribing information.
ADCETRIS (brentuximab vedotin) is an antibody-drug conjugate (ADC)
directed to CD30, a defining marker of classical Hodgkin lymphoma. Buy Huperzine online
ADCETRIS is currently approved in more than 55 countries for the
treatment of relapsed or refractory Hodgkin lymphoma and systemic
anaplastic large cell lymphoma (sALCL). http://cholesterolreviews.wordpress.com The utility of ADCETRIS is
currently being explored across a number of types of cancer, and data
from six studies in the ADCETRIS clinical trial program were presented
at the ASH meeting, including four as oral presentations.
“With more than 45 clinical trials across multiple lines of therapy
underway and ongoing research focused on understanding the underlying
pathogenesis of Hodgkin lymphoma, our commitment to advancing the care
of people battling this disease is far-reaching,” said Dirk Huebner,
M.D., Executive Medical Director, Oncology Therapeutic Area Unit, Takeda
Pharmaceutical Company. “The positive long-term results from these two
pivotal studies are very important in our work to advance the care of
people living with Hodgkin lymphoma whose disease has progressed.”
About the Studies
Study 1: Five-year Survival Data Demonstrating Durable Responses
from a Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with
Relapsed or Refractory Hodgkin Lymphoma [Abstract 2736, presented
December 6, 2015]
Five-year follow up data from the pivotal phase 2 study evaluating the
safety and efficacy of brentuximab vedotin in heavily pre-treated
patients with relapsed/refractory Hodgkin lymphoma post-ASCT were
presented as a poster by Robert Chen, M.D., City of Hope National
Medical Center, California. In the study, the 102 enrolled patients
received 1.8 mg/kg brentuximab vedotin once every three weeks as a 30
minute outpatient intravenous (IV) infusion for up to 16 cycles. The
primary endpoint was the objective response rate (ORR) per independent
review according to the Revised Response Criteria for Malignant Lymphoma
(Cheson 2007). Key secondary endpoints included complete response (CR)
rate, duration of response, PFS, OS, safety and tolerability. Survival
and disease status were assessed every three months for two years and
then every six months through year five. A study protocol amendment
removed the requirement of routine CT scanning during follow up, and so
disease status was assessed by the investigator. At the time of the
amendment, 18 patients were still being assessed for progression; these
patients had been in long-term follow-up for a median of over 30 months.
Patients received a median of nine cycles (range, 1-16) of brentuximab
vedotin. The study met its primary endpoint demonstrating 72 percent ORR
and a CR rate of 33 percent. The most common treatment-related adverse
events were peripheral sensory neuropathy, nausea, fatigue, neutropenia,
and diarrhea. Grade 3 or higher adverse events occurred in >=5 percent of
patients and included neutropenia, peripheral sensory neuropathy,
thrombocytopenia, and anemia.
Fifteen of the 102 enrolled patients remained in follow-up and in
remission at study closure. Of the 15 patients, six received
consolidative allogeneic SCT and nine received no further therapy since
completing treatment with brentuximab vedotin.
Study 2: Updated Efficacy and Safety Data from the AETHERA Trial
of Consolidation with Brentuximab Vedotin After Autologous Stem Cell
Transplant (ASCT) in Hodgkin Lymphoma Patients at High Risk of Relapse
[Abstract 3172, presented December 6, 2015]
Updated efficacy and safety data from the phase 3 AETHERA trial were
presented as a poster by John Sweetenham, M.D., Huntsman Cancer
Institute, University of Utah. The AETHERA trial was designed to
evaluate the potential of single-agent brentuximab vedotin to extend PFS
post-ASCT in patients with Hodgkin lymphoma with at least one risk
factor for progression. In addition to the primary endpoint of PFS,
secondary endpoints included OS, safety and tolerability. Eligible
patients must have had a history of refractory Hodgkin lymphoma, have
relapsed within one year from receiving frontline chemotherapy and/or
had extranodule disease at the time of pre-ASCT relapse. These factors
are consistently reported to be associated with poor prognosis after
transplant. Patients received brentuximab vedotin or placebo every three
weeks for up to approximately one year. This international multi-center
trial was conducted at 78 sites in the United States, Eastern and
Western Europe and Russia.
A total of 329 Hodgkin lymphoma patients at risk of relapse were
enrolled, including 165 on the brentuximab vedotin arm and 164 on the
placebo arm. Patients received a median of 15 cycles of treatment on
both arms.
As reported at the ASH annual meeting in 2014, the AETHERA trial met its
primary endpoint, demonstrating significant improvement in PFS among
patients who received brentuximab vedotin compared to patients who
received placebo (median of 43 months versus 24 months, respectively;
HR=0.57; p=0.001). Approximately three years after the last patient was
randomized, consolidation therapy with ADCETRIS continued to show an
improvement in PFS. At three years, PFS was 61 percent (95% CI:53–68)
for patients in the brentuximab vedotin arm compared to 43 percent (95%
CI 36-51) for the placebo arm.
At three years, treatment-emergent peripheral neuropathy resolved for
most patients, and no additional secondary malignancies were observed in
either treatment arm.
Among the 112 patients in the brentuximab vedotin arm who experienced
treatment-emergent peripheral neuropathy, 99 patients (88%)
experienced some improvement (23%) or complete resolution (65%) of
neuropathy symptoms at the time of analysis.
Secondary malignancies were comparable between the two treatment arms
(n=4 brentuximab vedotin, n=2 placebo).
Discontinuation of treatment due to an adverse event (AE) occurred in
54 patients (33%) who received ADCETRIS, most commonly due to
peripheral sensory and motor neuropathies (14% and 7%, respectively).
Patients who discontinued brentuximab vedotin treatment as a result of
an AE received a median of 9.5 cycles (range, 1 to 15). The two-year
PFS rate in these patients was 69 percent (95% CI 54–79) versus 82
percent (95% CI 71–89) for patients who completed all 16 treatment
cycles.
Six PFS events (2 progressions and 4 deaths) were recorded after the
24-month evaluation period in the brentuximab vedotin arm versus three
in the placebo arm (2 progressions and 1 death). The hazard ratio (HR)
for PFS per independent review was 0.57 (95% CI 0.41–0.82).
About ADCETRIS®
ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody attached
by a protease-cleavable linker to a microtubule disrupting agent,
monomethyl auristatin E (MMAE). The ADC employs a linker system that is
designed to be stable in the bloodstream but to release MMAE upon
internalization into CD30-expressing tumor cells.
ADCETRIS was granted conditional marketing authorization by the European
Commission in October 2012 for two indications: (1) for the treatment of
adult patients with relapsed or refractory CD30-positive Hodgkin
lymphoma following autologous stem cell transplant (ASCT), or following
at least two prior therapies when ASCT or multi-agent chemotherapy is
not a treatment option, and (2) the treatment of adult patients with
relapsed or refractory sALCL. ADCETRIS has received marketing
authorization by regulatory authorities in more than 55 countries. See
important safety information below.
ADCETRIS for intravenous injection has received approval from the FDA
for three indications: (1) regular approval for the treatment of
patients with classical Hodgkin lymphoma after failure of autologous
hematopoietic stem cell transplantation (auto-HSCT) or after failure of
at least two prior multi-agent chemotherapy regimens in patients who are
not auto-HSCT candidates, (2) regular approval for the treatment of
classical Hodgkin lymphoma patients at high risk of relapse or
progression as post-auto-HSCT consolidation, and (3) accelerated
approval for the treatment of patients with systemic anaplastic large
cell lymphoma (sALCL) after failure of at least one prior multi-agent
chemotherapy regimen. The sALCL indication is approved under accelerated
approval based on overall response rate. Continued approval for the
sALCL indication may be contingent upon verification and description of
clinical benefit in confirmatory trials. Health Canada granted ADCETRIS
approval with conditions for relapsed or refractory Hodgkin lymphoma and
sALCL.
ADCETRIS is being evaluated broadly in more than 30 ongoing clinical
trials, including the phase 3 ALCANZA trial and two additional phase 3
studies, one in frontline classical Hodgkin lymphoma and one in
frontline mature T-cell lymphomas, as well as trials in many additional
types of CD30-expressing malignancies, including B-cell lymphomas.
Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the
terms of the collaboration agreement, Seattle Genetics has U.S. and
Canadian commercialization rights and Takeda has rights to commercialize
ADCETRIS in the rest of the world. Seattle Genetics and Takeda are
funding joint development costs for ADCETRIS on a 50:50 basis, except in
Japan where Takeda is solely responsible for development costs.
ADCETRIS Global Important Safety Information
ADCETRIS® is indicated for the treatment of adult patients with relapsed
or refractory (r/r) CD30+ Hodgkin lymphoma (HL):
1. Following autologous stem cell transplant or
2. Following at least 2 prior therapies when autologous stem cell
transplantation is not a treatment option
ADCETRIS is indicated for the treatment of adult patients with relapsed
or refractory systemic anaplastic large cell lymphoma (sALCL).
ADCETRIS is contraindicated for patients who are hypersensitive to
ADCETRIS. In addition, combined use of bleomycin and ADCETRIS causes
pulmonary toxicity, and is contraindicated.
ADCETRIS can cause serious side effects, including:
Progressive multifocal leukoencephalopathy (PML): John
Cunningham virus (JCV) reactivation resulting in PML and death has
been reported in patients treated with ADCETRIS. Patients should be
closely monitored for new or worsening neurological, cognitive, or
behavioral signs or symptoms, which may be suggestive of PML.
Pancreatitis: Acute pancreatitis has been observed in patients
treated with ADCETRIS. Fatal outcomes have been reported. Patients
should be closely monitored for new or worsening abdominal pain.
Pulmonary Toxicity: Cases of pulmonary toxicity have been
reported in patients receiving ADCETRIS. In the event of new or
worsening pulmonary symptoms (e.g., cough, dyspnoea), a prompt
diagnostic evaluation should be performed.
Serious infections and opportunistic infections: Serious
infections such as pneumonia, staphylococcal bacteraemia,
sepsis/septic shock (including fatal outcomes), and herpes zoster, and
opportunistic infections such as Pneumocystis jiroveci pneumonia and
oral candidiasis have been reported in patients treated with ADCETRIS.
Patients should be carefully monitored during treatment for emergence
of possible serious and opportunistic infections.
Infusion-related reactions: Immediate and delayed
infusion-related reactions, as well as anaphylaxis, have occurred with
ADCETRIS. Patients should be carefully monitored during and after an
infusion.
Tumor lysis syndrome (TLS): TLS has been reported with
ADCETRIS. Patients with rapidly proliferating tumor and high tumor
burden are at risk of TLS and should be monitored closely and managed
according to best medical practice.
Peripheral neuropathy (PN): ADCETRIS treatment may cause PN
that is predominantly sensory. Cases of peripheral motor neuropathy
have also been reported. Patients should be monitored for symptoms of
PN, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a
burning sensation, neuropathic pain, or weakness.
Hematological toxicities: Grade 3 or Grade 4 anemia,
thrombocytopenia, and prolonged (equal to or greater than one week)
Grade 3 or Grade 4 neutropenia can occur with ADCETRIS. Complete blood
counts should be monitored prior to administration of each dose.
Febrile neutropenia: Febrile neutropenia has been reported.
Patients should be monitored closely for fever and managed according
to best medical practice.
Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): SJS
and TEN have been reported. Fatal outcomes have been reported.
Hyperglycemia: Hyperglycemia has been reported during trials in
patients with an elevated body mass index (BMI) with or without a
history of diabetes mellitus. Any patient who experiences an event of
hyperglycemia should have their serum glucose closely monitored.
Renal and hepatic impairment: There is limited experience
in patients with renal and hepatic impairment. Population
pharmacokinetic analysis indicated that MMAE clearance might be
affected by moderate and severe renal impairment, and by low serum
albumin concentrations. Elevations in alanine aminotransferase (ALT)
and aspartate aminotransferase (AST) have been reported. Liver
function should be routinely monitored in patients receiving
brentuximab vedotin.
Sodium content in excipients: This medicinal product contains a
maximum of 2.1 mmol (or 47mg) of sodium per dose. To be taken into
consideration for patients on a controlled sodium diet.
Serious adverse drug reactions were: neutropenia, thrombocytopenia,
constipation, diarrhea, vomiting, pyrexia, peripheral motor neuropathy
and peripheral sensory neuropathy, hyperglycemia, demyelinating
polyneuropathy, tumor lysis syndrome, and Stevens-Johnson syndrome.
ADCETRIS was studied as monotherapy in 160 patients in two Phase 2
studies. Across both studies, adverse reactions defined as very common
(>=1/10) were: infections, neutropenia, peripheral sensory neuropathy,
diarrhea, nausea, vomiting, alopecia, pruritis, myalgia, fatigue,
pyrexia, and infusion-related reactions. Adverse reactions defined as
common (>=1/100 to <1/10) were: upper respiratory tract infection, herpes
zoster, pneumonia, anemia, thrombocytopenia, hyperglycemia, peripheral
motor neuropathy, dizziness, demyelinating polyneuropathy, cough,
dyspnea, constipation, rash, arthralgia, back pain, and chills.
These are not all of the possible side effects with ADCETRIS. Please
refer to Summary of Product Characteristics (SmPC) before prescribing.
About Takeda
Located in Osaka, Japan, Takeda (TSE:4502)
is a research-based global company with its main focus on
pharmaceuticals. As the largest pharmaceutical company in Japan and one
of the global leaders of the industry, Takeda is committed to strive
towards better health for people worldwide through leading innovation in
medicine.
Additional information about Takeda is available through its corporate
website, .takeda.com.
Subscribe to:
Posts (Atom)