ction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice.
The adverse drug reactions (ADRs) described in this section were identified from Trial 1 and Trial 2 [see Clinical Studies (14)]. In Trial 1, treatment naive patients with unresectable or metastatic melanoma (n=675) were allocated to ZELBORAF 960 mg orally twice daily or to dacarbazine 1000 mg/m2 intravenously every 3 weeks. In Trial 2, (n=132) patients with metastatic melanoma and failure of at least one prior systemic therapy received treatment with ZELBORAF 960 mg orally twice daily. Adverse reactions reported in at least 10% of patients treated with ZELBORAF are presented in Table 2. The most common adverse reactions of any grade (≥ 30% in either study) reported in ZELBORAF-treated patients were arthralgia, rash, alopecia, fatigue, photosensitivity reaction, nausea, pruritus and skin papilloma. The most common (≥ 5%) Grade 3 adverse reactions were cuSCC and rash. The incidence of Grade 4 adverse reactions was ≤ 4% in both studies.
The incidence of adverse events resulting in permanent discontinuation of study medication in Trial 1 was 7% for the ZELBORAF arm and 4% for the dacarbazine arm. In Trial 2, the incidence of adverse events resulting in permanent discontinuation of study medication was 3% in ZELBORAF-treated patients. The median duration of study treatment was 4.2 months for ZELBORAF and 0.8 months for dacarbazine in Trial 1, and 5.7 months for ZELBORAF in Trial 2.
Table 2 Adverse Reactions Reported in ≥ 10% of Patients Treated with ZELBORAF* Trial 1: Treatment Naive Patients Trial 2: Patients with Failure of at Least One Prior Systemic Therapy
ZELBORAF
n= 336 Dacarbazine
n= 287 ZELBORAF
n= 132
ADRs All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Skin and subcutaneous tissue disorders
Rash 37 8 - 2 - - 52 7 -
Photosensitivity reaction 33 3 - 4 - - 49 3 -
Alopecia 45 <1 - 2 - - 36 - -
Pruritus 23 1 - 1 - - 30 2 -
Hyperkeratosis 24 1 - <1 - - 28 - -
Rash maculo-papular 9 2 - <1 - - 21 6 -
Actinic keratosis 8 - - 3 - - 17 - -
Dry skin 19 - - 1 - - 16 - -
Rash papular 5 <1 - - - - 13 - -
Erythema 14 - - 2 - - 8 - -
Musculoskeletal and connective tissue disorders
Arthralgia 53 4 - 3 <1 - 67 8 -
Myalgia 13 <1 - 1 - - 24 <1 -
Pain in extremity 18 <1 - 6 2 - 9 - -
Musculoskeletal pain 8 - - 4 <1 - 11 - -
Back pain 8 <1 - 5 <1 - 11 <1 -
General disorders and administration site conditions
Fatigue 38 2 - 33 2 - 54 4 -
Edema peripheral 17 <1 - 5 - - 23 - -
Pyrexia 19 <1 - 9 <1 - 17 2 -
Asthenia 11 <1 - 9 <1 - 2 - -
Gastrointestinal disorders
Nausea 35 2 - 43 2 - 37 2 -
Diarrhea 28 <1 - 13 <1 - 29 <1 -
Vomiting 18 1 - 26 1 - 26 2 -
Constipation 12 <1 - 24 - - 16 - -
Nervous system disorders
Headache 23 <1 - 10 - - 27 - -
Dysgeusia 14 - - 3 - - 11 - -
Neoplasms benign, malignant and unspecified (includes cysts and polyps) &nb |
