TAZVERIK SIDE EFFECTS

  • Generic Name: tazemetostat tablets
  • Brand Name: Tazverik
  • Drug Class: EZH2 Inhibitors
Last updated on MDtodate: 10/12/2022

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in labeling:

  • Secondary Malignancies

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.

Epithelioid Sarcoma

The safety of TAZVERIK was evaluated in a cohort (Cohort 5) of Study EZH-202 that enrolled patients with epithelioid sarcoma. Patients received TAZVERIK 800 mg orally twice daily (n=62). Among patients who received TAZVERIK, 44% were exposed for 6 months or longer and 24% were exposed for greater than one year.

Serious adverse reactions occurred in 37% of patients who received TAZVERIK. Serious adverse reactions in ≥3% of patients who received TAZVERIK were hemorrhage, pleural effusion, skin infection, dyspnea, pain, and respiratory distress.

One patient (2%) permanently discontinued TAZVERIK due to an adverse reaction of altered mood.

Dosage interruptions due to an adverse reaction occurred in 34% of patients who received TAZVERIK. The most frequent adverse reactions requiring dosage interruptions in ≥3% were hemorrhage, increased alanine aminotransferase (ALT), and increased aspartate aminotransferase (AST).

Dose reduction due to an adverse reaction occurred in one (2%) patient who received TAZVERIK; the dose was reduced in this patient for decreased appetite.

The most common adverse reactions (≥20%) were pain, fatigue, nausea, decreased appetite, vomiting, and constipation.

Table 1 presents adverse reactions in patients with epithelioid sarcoma in Cohort 5 of Study EZH-202.

Table 1: Adverse Reactions (≥10%) in Patients with Epithelioid Sarcoma Who Received TAZVERIK in Cohort 5 of Study EZH-202

Adverse Reaction TAZVERIK
N=62
All Grades (%) Grade 3 or 4 (%)
General
Paina 52 7
Fatigueb 47 1.6
Gastrointestinal
Nausea 36 0
Vomiting 24 0
Constipation 21 0
Diarrhea 16 0
Abdominal painc 13 1.6
Metabolism and nutrition
Decreased appetite 26 4.8
Respiratory, thoracic and mediastinal
Cough 18 0
Dyspnead 16 4.8
Vascular
Hemorrhagee 18 4.8
Nervous system
Headache 18 0
Investigations
Weight decreased 16 7
a Includes tumor pain, pain in extremity, non-cardiac chest pain, flank pain, back pain, arthralgia, bone pain, cancer pain, musculoskeletal pain, myalgia, neck pain
b Includes fatigue and asthenia
c Includes abdominal pain, gastrointestinal pain, abdominal pain lower
d Includes dyspnea and dyspnea exertional
e Includes wound hemorrhage, rectal hemorrhage, pulmonary hemorrhage, hemorrhage intracranial, cerebral hemorrhage, hemoptysis

 

Table 2 summarizes select laboratory abnormalities in patients with epithelioid sarcoma in Cohort 5 of Study EZH-202.

Table 2: Select Laboratory Abnormalities (≥ 10%) Worsening from Baseline in Patients with Epithelioid Sarcoma Who Received TAZVERIK in Cohort 5 of Study EZH-202

Laboratory Abnormality TAZVERIK*
All Grades (%) Grade 3 or 4 (%)
Hematology
Decreased hemoglobin 49 15
Decreased lymphocytes 36 13
Decreased white blood cell count 19 0
Chemistry
Increased triglycerides 36 3.3
Increased glucose 33 1.6
Decreased sodium 30 1.7
Decreased phosphate 28 1.7
Decreased albumin 23 0
Increased alkaline phosphatase 23 1.7
Decreased potassium 20 1.7
Increased aspartate aminotransferase 18 3.5
Decreased calcium 16 0
Decreased glucose 16 0
Increased partial thromboplastin time 15 5
Increased alanine aminotransferase 14 3.4
Increased creatinine 12 0
Increased potassium 12 0
*The denominator used to calculate the rate varied from 39 to 61 based on the number of patients with a baseline value and at least one post-treatment value.

 

Relapsed Or Refractory Follicular Lymphoma

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. 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 3 presents adverse reactions in patients with relapsed or refractory follicular lymphoma in Cohorts 4 and 5 of Study E7438-G000-101.

Table 3: 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 TAZVERIK
N=99
All Grades (%) Grade 3 or 4 (%)
General
Fatiguea 36 5
Pyrexia 10 0
Infections
Upper respiratory tract infectionb 30 0
Lower respiratory tract infectionc 17 0
Urinary tract infectiond 11 2
Gastrointestinal
Nausea 24 1
Abdominal paine 20 3
Diarrhea 18 0
Vomiting 12 1
Musculoskeletal and connective tissue
Musculoskeletal painf 22 1
Skin and subcutaneous tissue
Alopecia 17 0
Rashg 15 0
Respiratory and mediastinal system
Coughh 17 0
Nervous system
Headachei 13 0
a Includes fatigue and asthenia
b Includes laryngitis, nasopharyngitis, pharyngitis, rhinitis, sinusitis, upper repiratory tract infection, viral upper respiratory tract infection
c Includes bronchitis, lower respiratory tract infection, tracheobronchitis
d Includes cystitis, urinary tract infection, urinary tract infection staphylococcal
e Includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper
f Includes back pain, limb discomfort, musculoskeletal chest pain, musculoskeletal discomfort, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain in extremity, pain in jaw, spinal pain
g Includes erythema, rash, rash erythematous, rash generalized, rash maculo-papular, rash pruritic, rash pustular, skin exfoliation
h Includes cough and productive cough
i Includes headache, migraine, sinus headache

 

Clinically relevant adverse reactions occurring in <10% of patients who received TAZVERIK included:

  • Infection: sepsis (2%), pneumonia (2%), and herpes zoster (2%)

Table 4 summarizes select laboratory abnormalities in patients with follicular lymphoma in Cohorts 4 and 5 of Study E7438-G000-101.

Table 4: Select Laboratory Abnormalities (≥10%) Worsening from Baseline in Patients with Relapsed or Refractory Follicular Lymphoma Who Received TAZVERIK in Cohorts 4 and 5 of Study E7438-G000-101

Laboratory Abnormality TAZVERIK*
All Grades (%) Grade 3 or 4 (%)
Hematology
Decreased lymphocytes 57 18
Decreased hemoglobin 50 8
Decreased platelets 50 7
Decreased white blood cells 41 9
Decreased neutrophils 20 7
Chemistry
Increased glucose 53 10
Increased aspartate aminotransferase 24 0
Increased alanine aminotransferase 21 2.3
Increased alkaline phosphatase 18 1.0
Increased creatinine 17 0
*The denominator used to calculate the rate varied from 88 to 96 based on the number of patients with a baseline value and at least one post-treatment value.

 

SRC: NLM .