VIZIMPRO SIDE EFFECTS
- Generic Name: dacomitinib
- Brand Name: Vizimpro
- Drug Class: Antineoplastics EGFR Inhibitors, Antineoplastic Tyrosine Kinase Inhibitors
SIDE EFFECTS
The following adverse drug reactions are described elsewhere in the labeling:
- Interstitial Lung Disease.
- Diarrhea.
- Dermatologic Adverse Reactions.
Clinical Trials 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data in the Warnings and Precautions section reflect exposure to VIZIMPRO in 394 patients with first-line or previously treated NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations who received VIZIMPRO at the recommended dose of 45 mg once daily in 4 randomized, active-controlled trials [ARCHER 1050 (N=227), Study A7471009 (N=38), Study A7471011 (N=83), and Study A7471028 (N=16)] and one single-arm trial [Study A7471017 (N=30)]. The median duration of exposure to VIZIMPRO was 10.8 months (range 0.07-68).
The data described below reflect exposure to VIZIMPRO in 227 patients with EGFR mutation-positive, metastatic NSCLC enrolled in a randomized, active-controlled trial (ARCHER 1050); 224 patients received gefitinib 250 mg orally once daily in the active control arm. Patients were excluded if they had a history of ILD, interstitial pneumonitis, or brain metastases. The median duration of exposure to VIZIMPRO was 15 months (range 0.07-37).
The most common (>20%) adverse reactions in patients treated with VIZIMPRO were diarrhea (87%), rash (69%), paronychia (64%), stomatitis (45%), decreased appetite (31%), dry skin (30%), decreased weight (26%), alopecia (23%), cough (21%), and pruritus (21%).
Serious adverse reactions occurred in 27% of patients treated with VIZIMPRO. The most common (≥1%) serious adverse reactions were diarrhea (2.2%) and interstitial lung disease (1.3%). Dose interruptions occurred in 57% of patients treated with VIZIMPRO. The most frequent (>5%) adverse reactions leading to dose interruptions were rash (23%), paronychia (13%), and diarrhea (10%). Dose reductions occurred in 66% of patients treated with VIZIMPRO. The most frequent (>5%) adverse reactions leading to dose reductions were rash (29%), paronychia (17%), and diarrhea (8%).
Adverse reactions leading to permanent discontinuation of VIZIMPRO occurred in 18% of patients. The most common (>0.5%) adverse reactions leading to permanent discontinuation of VIZIMPRO were: rash (2.6%), interstitial lung disease (1.8%), stomatitis (0.9%), and diarrhea (0.9%).
Tables 1 and 2 summarize the most common adverse reactions and laboratory abnormalities, respectively, in ARCHER 1050. ARCHER 1050 was not designed to demonstrate a statistically significant difference in adverse reaction rates for VIZIMPRO or for gefitinib for any adverse reaction or laboratory value listed in Table 1 or 2.
Table 1. Adverse Reactions Occurring in ≥10% of Patients Receiving VIZIMPRO in ARCHER 1050*
| Adverse Reaction | VIZIMPRO (N=227) |
Gefitinib (N=224) |
||
| All Gradesa % |
Grades 3 and 4 % |
All Grades % |
Grades 3 and 4 % |
|
| Gastrointestinal | ||||
| Diarrheab | 87 | 8 | 56 | 0.9 |
| Stomatitisc | 45 | 4.4 | 19 | 0.4 |
| Nausea | 19 | 1.3 | 22 | 0.4 |
| Constipation | 13 | 0 | 14 | 0 |
| Mouth ulceration | 12 | 0 | 6 | 0 |
| Skin and Subcutaneous Tissue | ||||
| Rashd | 69 | 23 | 47 | 0.4 |
| Paronychiae | 64 | 8 | 21 | 1.3 |
| Dry skinf | 30 | 1.8 | 19 | 0.4 |
| Alopecia | 23 | 0.4 | 13 | 0 |
| Pruritusg | 21 | 0.9 | 15 | 1.3 |
| Palmar-plantar erythrodysesthesia syndrome | 15 | 0.9 | 3.1 | 0 |
| Dermatitis | 11 | 1.8 | 4 | 0.4 |
| Metabolism and Nutrition | ||||
| Decreased appetite | 31 | 3.1 | 25 | 0.4 |
| Decreased weight | 26 | 2.2 | 17 | 0.4 |
| Respiratory | ||||
| Cough | 21 | 0 | 19 | 0.4 |
| Nasal mucosal disorderh | 19 | 0 | 4.9 | 0 |
| Dyspnea | 13 | 2.2 | 13 | 1.8 |
| Upper respiratory tract infection | 12 | 1.3 | 13 | 0 |
| Chest pain | 10 | 0 | 14 | 0 |
| Eye | ||||
| Conjunctivitis | 19 | 0 | 4 | 0 |
| Musculoskeletal | ||||
| Pain in extremity | 14 | 0 | 12 | 0 |
| Musculoskeletal pain | 12 | 0.9 | 13 | 0 |
| General | ||||
| Asthenia | 13 | 2.2 | 13 | 1.3 |
| Psychiatric | ||||
| Insomnia | 11 | 0.4 | 15 | 0 |
| * National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03. a Grades 1 through 5 are included in All Grades. b One Grade 5 (fatal) event in the VIZIMPRO arm. c Stomatitis includes mucosal inflammation and stomatitis. d Rash includes dermatitis acneiform, rash, and rash maculo-papular. e Paronychia includes nail infection, nail toxicity, onychoclasis, onycholysis, onychomadesis, paronychia. f Dry skin includes dry skin, xerosis. g Pruritus includes pruritus, pruritus generalized, rash pruritic. h Nasal mucosal disorder includes epistaxis, nasal inflammation, nasal mucosal disorder, nasal mucosal ulcer, rhinitis. |
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Additional adverse reactions (All Grades) that were reported in <10% of patients who received VIZIMPRO in ARCHER 1050 include:
General: fatigue 9%
Skin and subcutaneous tissue: skin fissures 9%, hypertrichosis 1.3%, skin exfoliation/exfoliative skin reactions 3.5%
Gastrointestinal: vomiting 9%
Nervous system: dysgeusia 7%
Respiratory: interstitial lung disease 2.6%
Ocular: keratitis 1.8%
Metabolism and nutrition: dehydration 1.3%
Table 2. Laboratory Abnormalities Worsening from Baseline in >20% of Patients in ARCHER 1050*
| Laboratory Test Abnormalitya | VIZIMPRO | Gefitinib | ||
| Change from Baseline All Grades (%) |
Change from Baseline to Grade 3 or Grade 4 (%) |
Change from Baseline All Grades (%) |
Change from Baseline to Grade 3 or Grade 4 (%) |
|
| Hematology | ||||
| Anemia | 44 | 0.9 | 26 | 2.7 |
| Lymphopenia | 42 | 6 | 35 | 2.7 |
| Chemistry | ||||
| Hypoalbuminemia | 44 | 0 | 34 | 0 |
| Increased ALT | 40 | 1.4 | 63 | 13 |
| Hyperglycemia | 36 | 1.0 | 38 | 2.5 |
| Increased AST | 35 | 0.5 | 57 | 8 |
| Hypocalcemia | 33 | 1.4 | 28 | 2.0 |
| Hypokalemia | 29 | 7 | 18 | 2.8 |
| Hyponatremia | 26 | 2.9 | 20 | 1.5 |
| Increased creatinine | 24 | 0 | 16 | 0.5 |
| Increased alkaline phosphatase | 22 | 0.5 | 21 | 2.0 |
| Hypomagnesemia | 22 | 0.5 | 9 | 0 |
| Hyperbilirubinemia | 16 | 0.5 | 22 | 0.5 |
| ALT=alanine aminotransferase; AST=aspartate aminotransferase. *NCI CTCAE v4.03, except for increased creatinine which only includes patients with creatinine increase based on upper limit of normal definition. a Based on the number of patients with available baseline and at least one on-treatment laboratory test. |
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SRC: NLM .