atigue, nausea, alopecia, constipation, peripheral neuropathy, abdominal pain, and pyrexia. The most common (≥5%) Grade 3-4 laboratory abnormalities reported in patients receiving HALAVEN were neutropenia, hypokalemia, and hypocalcemia. The most common serious adverse reactions reported in patients receiving HALAVEN were neutropenia (4.9 %) and pyrexia (4.5%). Permanent discontinuation of HALAVEN for adverse reactions occurred in 8% of patients. The most common adverse reactions resulting in discontinuation of HALAVEN were fatigue and thrombocytopenia (0.9% each). Twenty-six percent of patients required at least one dose reduction. The most frequent adverse reactions that led to dose reduction were neutropenia (18%) and peripheral neuropathy (4.0%).
Table 3 summarizes the incidence of adverse reactions occurring in at least 10% of patients in the HALAVEN-treated arm in Study 2.
Table 3: Adverse Reactionsa Occurring in ≥10% (all Grades) of Patients Treated on the HALAVEN arm and at a Higher Incidence than in the Dacarbazine Arm (Between Arm Difference of ≥5% for All Grades or ≥2% for Grades 3 and 4) (Study 2)b
Adverse Reaction HALAVEN
n=223 Dacarbazine
n=221
All Grades Grades 3-4 All Grades Grades 3-4
Nervous system disorders
Peripheral Neuropathyc 29% 3.1% 8% 0.5%
Headache 18% 0% 10% 0%
General disorders
Pyrexia 28% 0.9% 14% 0.5%
Gastrointestinal disorders
Constipation 32% 0.9% 26% 0.5%
Abdominal paind 29% 1.8% 23% 4.1%
Stomatitis 14% 0.9% 5% 0.5%
Skin and subcutaneous tissue disorders
Alopecia 35% NAe 2.7% NAe
Infections
Urinary tract infection 11% 2.2% 5% 0.5%
a Adverse reactions were graded per National Cancer Institute Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03).
b Safety data from one study site enrolling six patients were excluded.
cIncludes peripheral neuropathy, peripheral sensorimotor neuropathy, peripheral motor neuropathy, polyneuropathy, peripheral sensory neuropathy, and paraesthesia
d Includes abdominal pain, upper abdominal pain, lower abdominal pain, abdominal discomfort
e Not applicable; (grading system does not specify > Grade 2 for alopecia)
Other clinically important adverse reactions occurring in ≥10% of the HALAVEN-treated patients were:
Gastrointestinal Disorders: nausea (41%); vomiting (19%), diarrhea (17%)
General Disorders: asthenia/fatigue (62%); peripheral edema (12%)
Metabolism and Nutrition Disorders: decreased appetite (19%)
Musculoskeletal and Connective Tissue Disorders: arthralgia/myalgia (16%); back pain (16%)
Respiratory Disorders: cough (18%)
Less Common Adverse Reactions: The following additional clinically important adverse reactions were reported in ≥5% to <10% of the HALAVEN-treated group:
Blood and Lymphatic System Disorders: thrombocytopenia
Eye Disorders: increased lacrimation
Gastrointestinal Disorders: dyspepsia
Metabolism and Nutrition Disorders: hyperglycemia
Musculoskeletal and Connective Tissue Disorders: muscle spasms, musculoskeletal pain
Nervous System Disorders: dizziness, dysgeusia
Psychiatric Disorders: insomnia, anxiety
Respiratory, Thoracic, and Mediastinal Disorders: oropharyngeal pain
Vascular Disorders: hypotension
Table 4: Laboratory Abnormalities Occurring in ≥10% (all Grades) of Patients Treated on the HALAVEN arm and at a H |
