NEWS
responses were improved in both treatment arms, but
QoL appeared better in the zanubrutinib group.
In the MYD88 WT group, the major response rate with
zanubrutinib was 50% and the VGPR rate was 26.9%; CRs
were not observed. PFS at 12 months was 72%.
“True to our study hypothesis,” said Dr. Tam, “zanubrutinib,
being a more targeted drug, may be associated
with fewer side effects and better tolerability.”
The authors disclosed interests with BeiGene,
which funded the study.
Reference
Tam C, Opat S, D’Sa S, et al. ASPEN: Results of a phase III randomized trial of
zanubrutinib versus ibrutinib for patients with Waldenström macroglobulinemia
(WM). Abstract 8007. Presented as part of the ASCO20 Virtual Scientific
Program. May 29-31, 2020.
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TAZVERIK (tazemetostat) tablets 200mg BRIEF SUMMARY OF PRESCRIBING
INFORMATION
CONSULT THE PACKAGE INSERT FOR COMPLETE PRESCRIBING INFORMATION.
INDICATIONS AND USAGE
• TAZVERIK™ (tazemetostat) is indicated for the treatment of adult patients with
relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2
mutation as detected by an FDA-approved test and who have received at least 2 prior
systemic therapies.
• TAZVERIK is indicated for the treatment of adult patients with relapsed or refractory
follicular lymphoma who have no satisfactory alternative treatment options.
These indications are approved under accelerated approval based on overall response
rate and duration of response [see Clinical Studies]. Continued approval for these
indications may be contingent upon verification and description of clinical benefit in
a confirmatory trial(s).
DOSAGE AND ADMINISTRATION
Patient Selection - Select patients with relapsed or refractory (R/R) follicular
lymphoma (FL) for treatment with TAZVERIK based on the presence of EZH2 mutation
of codons Y646, A682, or A692 in tumor specimens [see Clinical Studies]. Information
on FDA-approved tests for the detection of EZH2 mutation in relapsed or refractory
follicular lymphoma is available at: http://www.fda.gov/CompanionDiagnostics.
Recommended Dosage - The recommended dosage of TAZVERIK is 800 mg orally
twice daily with or without food until disease progression or unacceptable toxicity.
Swallow tablets whole. Do not cut, crush, or chew tablets. Do not take an additional
dose if a dose is missed or vomiting occurs after TAZVERIK, but continue with the
next scheduled dose.
Dosage Modifications for Adverse Reactions - Table 1 summarizes the recommended
dose reductions, and Table 2 summarizes the recommended dosage modifications of
TAZVERIK for adverse reactions.
Table 1. Recommended Dose Reductions of TAZVERIK for Adverse Reactions
Dose Reduction
First
Second
Dosage
600 mg orally twice daily
400 mg orally twice daily*
*Permanently discontinue TAZVERIK in patients who are unable to tolerate 400 mg orally
twice daily.
Table 2. Recommended Dosage Modifications of TAZVERIK for Adverse Reactions
Adverse Reaction Severity Dosage Modification
Neutropenia [see
Adverse Reactions]
Thrombocytopenia
[see Adverse
Reactions]
Anemia
[see Adverse
Reactions]
Other adverse
reactions
[see Adverse
Reactions]
Neutrophil
count less
than 1 x 10 9 /L
Platelet count
less than
50 x 10 9 /L
Hemoglobin
less than
8 g/dL
Grade 3
Grade 4
• Withhold until neutrophil count is greater
than or equal to 1 x 10 9 /L or baseline.
• For first occurrence, resume at same dose.
• For second and third occurrence, resume
at reduced dose.
• Permanently discontinue after fourth
occurrence.
• Withhold until platelet count is greater
than or equal to 75 x 10 9 /L or baseline.
• For first and second occurrence, resume
at reduced dose.
• Permanently discontinue after third
occurrence.
• Withhold until improvement to at least
Grade 1 or baseline, then resume at
same or reduced dose.
• Withhold until improvement to at least
Grade 1 or baseline.
• For first and second occurrence, resume
at reduced dose.
• Permanently discontinue after third
occurrence.
• Withhold until improvement to at least
Grade 1 or baseline.
• For first occurrence, resume at
reduced dose.
• Permanently discontinue after second
occurrence.
Dosage Modifications for Drug Interactions
Strong and Moderate CYP3A Inhibitors - Avoid coadministration of TAZVERIK with strong
or moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot
be avoided, reduce the TAZVERIK dose as shown in Table 3 below. After discontinuation of
the moderate CYP3A inhibitor for 3 elimination half-lives, resume the TAZVERIK dose that
was taken prior to initiating the inhibitor [see Drug Interactions, Clinical Pharmacology].
Table 3. Recommended Dose Reductions of TAZVERIK for Moderate CYP3A Inhibitors
Current Dosage
Adjusted Dosage
800 mg orally twice daily 400 mg orally twice daily
600 mg orally twice daily
400 mg for first dose and 200 mg
for second dose
400 mg orally twice daily 200 mg orally twice daily
CONTRAINDICATIONS - None.
WARNINGS AND PRECAUTIONS
Secondary Malignancies - The risk of developing secondary malignancies is increased
following treatment with TAZVERIK. Across clinical trials of 729 adults who received
TAZVERIK 800 mg twice daily, myelodysplastic syndrome (MDS) or acute myeloid
leukemia (AML) occurred in 0.7% of patients. One pediatric patient developed T-cell
lymphoblastic lymphoma (T-LBL). Monitor patients long-term for the development of
secondary malignancies.
Embryo-Fetal Toxicity - Based on findings from animal studies and its mechanism of
action, TAZVERIK can cause fetal harm when administered to pregnant women. There
are no available data on TAZVERIK use in pregnant women to inform the drug-associated
risk. Administration of tazemetostat to pregnant rats and rabbits during organogenesis
resulted in dose-dependent increases in skeletal developmental abnormalities in both
species beginning at maternal exposures approximately 1.5 times the adult human
exposure (area under the plasma concentration time curve [AUC 0-45h]) at the 800 mg
twice daily dose. Advise pregnant women of the potential risk to a fetus. Advise females
of reproductive potential to use effective contraception during treatment with TAZVERIK
and for 6 months after the final dose. Advise males with female partners of reproductive
potential to use effective contraception during treatment with TAZVERIK and for 3 months
after the final dose [see Use in Specific Populations].
ADVERSE REACTIONS - The following clinically significant adverse reactions are
described elsewhere in labeling: Secondary Malignancies [see Warnings and Precautions].
Clinical Trial Experience - Because clinical trials are conducted under widely varying
conditions, adverse reaction rates observed in the clinical trials of a drug cannot be
directly compared with rates in the clinical trials of another drug and may not reflect the
rates observed in practice. The safety of TAZVERIK was evaluated in two cohorts (Cohorts
4 and 5) of Study E7438-G000-101 that enrolled patients with relapsed or refractory
follicular lymphoma [see Clinical Studies]. Patients received TAZVERIK 800 mg orally twice
daily (n=99). Among patients who received TAZVERIK, 68% were exposed for 6 months
or longer, 39% were exposed for 12 months or longer, and 21% were exposed for 18
months or longer. The median age was 62 years (range 36 to 87 years), 54% were male,
and 95% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
The median number of prior therapies was 3 (range 1 to 11). Patients were required have
a creatinine clearance ≥40 mL/min per the Cockcroft and Gault formula. Serious adverse
reactions occurred in 30% of patients who received TAZVERIK. Serious adverse reactions
in ≥2% of patients who received TAZVERIK were general physical health deterioration,
abdominal pain, pneumonia, sepsis, and anemia. Permanent discontinuation due
to an adverse reaction occurred in 8% of patients who received TAZVERIK. Adverse
reaction resulting in permanent discontinuation in ≥2% of patients was second primary
malignancy. Dosage interruptions due to an adverse reaction occurred in 28% of patients
who received TAZVERIK. Adverse reactions requiring dosage interruptions in ≥3% of
patients were thrombocytopenia and fatigue. Dose reduction due to an adverse reaction
occurred in 9% of patients who received TAZVERIK. The most common adverse reactions
(≥20%) were fatigue, upper respiratory tract infection, musculoskeletal pain, nausea, and
abdominal pain. Table 6 presents adverse reactions in patients with relapsed or refractory
follicular lymphoma in Cohorts 4 and 5 of Study E7438-G000-101.
Table 6. Adverse Reactions (≥10%) in Patients with Relapsed or Refractory Follicular
Lymphoma Who Received TAZVERIK in Cohorts 4 and 5 of Study E7438-G000-101
Adverse Reaction
General
TAZVERIK N=99
All Grades (%) Grade 3 or 4 (%)
Fatigue a 36 5
Pyrexia 10 0
Infections
Upper respiratory tract infection b 30 0
Lower respiratory tract infection c 17 0
Urinary tract infection d 11 2
Gastrointestinal
Nausea 24 1
Abdominal pain e 20 3
Diarrhea 18 0
Vomiting 12 1
Musculoskeletal and connective tissue
Musculoskeletal pain f 22 1
Skin and subcutaneous tissue
Alopecia 17 0
Rash g 15 0
Respiratory and mediastinal system
Cough h 17 0
Nervous system
Headache i 13 0
Table 6 continues on the next page