Adverse Reactions in ≥10% (All Gradesa) or ≥2% (Grades 3-4) of Patients by Arm in ALTA 1L (N=273)
|Gastroesophageal reflux disease||0.7||0||11||0|
|Skin and Subcutaneous Tissue Disorders|
|Respiratory, Thoracic and Mediastinal Disorders|
|General Disorders and Administration Site Conditions|
|Musculoskeletal and Connective Tissue Disorders|
|Pain in extremity||5.1||0||15||0.7|
|Nervous System Disorders|
|Increased blood cholesterolm||13||0||0.7||0|
|Infections and Infestations|
|Upper respiratory tract infectionp||12||0||10||0|
|Urinary tract infection||5.9||0.7||8.8||2.2|
|Metabolism and Nutrition Disorders|
aPer National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
bIncludes abdominal discomfort, abdominal distension, abdominal pain, abdominal pain lower, abdominal pain upper, and epigastric discomfort.
cIncludes aphthous ulcer, mouth ulceration, oral mucosal blistering and stomatitis.
dIncludes dermatitis, dermatitis acneiform, dermatitis bullous, dermatitis contact, drug eruption, erythema, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, toxic skin eruption, urticaria.
eIncludes pruritus, allergic pruritus, and generalized pruritus.
fIncludes dyspnea and exertional dyspnea.
gIncludes hypertension and systolic hypertension.
hIncludes asthenia and fatigue.
iIncludes angioedema, eye swelling, eyelid edema, face edema, generalized edema, lip swelling, peripheral edema, periorbital edema, peripheral swelling, skin swelling, swelling and swelling face.
jIncludes muscle spasms, muscle twitching, musculoskeletal discomfort, musculoskeletal pain, and myalgia.
kIncludes headache and migraine.
lIncludes burning sensation, dysesthesia, hyperesthesia, hypoesthesia, neuralgia, peripheral neuropathy, paraesthesia, peripheral sensory neuropathy and polyneuropathy.
mIncludes blood cholesterol increased, hypercholesterolemia.
nIncludes bradycardia, heart rate decreased, sinus bradycardia.
oIncludes lower respiratory tract infection, lung infection, pneumonia, aspiration pneumonia, and cryptococcal pneumonia.
pIncludes upper respiratory tract infection and viral upper respiratory tract infection.
qIncludes cataract, glaucoma, hypermetropia, night blindness, papilloedema, photophobia, photopsia, blurred vision, reduced visual acuity, visual field defect, visual impairment, and vitreous floaters.
rIncludes Grade 5 events.
Laboratory Abnormalities in ≥20% (All Gradesa) of Patients by Arm in ALTA 1L (N=273)
|Increased creatine phosphokinase||81||24||68||4.8|
|Increased aspartate aminotransferase||72||4.5||70||5.2|
|Increased alanine aminotransferase||52||5.2||77||13|
|Increased alkaline phosphatase||36||3||49||1.5|
|Lymphocyte count decreased||42||9.3||30||5.4|
|Neutrophil count decreased||12||0||34||6.8|
aPer NCI CTCAE v4.0.
bDenominator for each laboratory parameter may vary and is defined as the number of patients who had both baseline and post-baseline test.
cElevated blood insulin was also observed in both arms.
Serious adverse reactions occurred in 33% of patients receiving ALUNBRIG® (brigatinib). The most common serious adverse reactions were pneumonia (4.4%), ILD/pneumonitis (3.7%), pyrexia (2.9%), dyspnea (2.2%), pulmonary embolism (2.2%), and asthenia (2.2%). Fatal adverse reactions occurred in 2.9% of patients and included pneumonia (1.5%), cerebrovascular accident (0.7%), and multiple organ dysfunction syndrome (0.7%).
In ALTA 1L, 13% of patients receiving ALUNBRIG permanently discontinued ALUNBRIG for adverse reactions. The most frequent adverse reactions that led to discontinuation were ILD/pneumonitis (3.7%) and pneumonia (2.2%).
In ALTA 1L, 38% of patients required a dose reduction due to adverse reactions. The most common adverse reaction that led to dose reduction was increased creatine phosphokinase (15%), increased lipase (6.6%), increased amylase (4.4%), increased aspartate aminotransferase (2.2%), ILD/pneumonitis (2.2%) and hypertension (2.2%).
The median duration of treatment with ALUNBRIG was 24.3 months.
The median relative dose intensity was 97% for ALUNBRIG.
Interstitial lung disease/pneumonitis
- In the first-line phase 3 trial (ALTA 1L): ILD/pneumonitis occurred in 5.1% of patients receiving ALUNBRIG. ILD/pneumonitis occurred within 8 days of initiation of ALUNBRIG in 2.9% of patients, with Grade 3 to 4 reactions occurring in 2.2% of patients
- In the post-crizotinib phase 2 trial (ALTA): ILD/pneumonitis occurred in 9.1% of patients. Adverse reactions consistent with possible ILD/pneumonitis occurred within
9 daysof initiation of ALUNBRIG (median onset was 2 days) in 6.4% of patients, with Grade 3 to 4 reactions occurring in 2.7%