Choose ALUNBRIG® (brigatinib): A Well-Established Safety Profile

Chart showing adverse reactions reported by participants in ALTA 1L.
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.

Serious adverse reactions occurred in 33% of patients receiving ALUNBRIG.1

The most common serious adverse reactions in ALTA 1L were pneumonia (4.4%), ILD/pneumonitis (3.7%), pyrexia (2.9%), dyspnea (2.2%), pulmonary embolism (2.2%), and asthenia (2.2%).1

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%).1

Laboratory Abnormalities in ≥20% (All Gradesa) of Patients by Arm in ALTA 1L (N=273)1

Chart showing laboratory abnormalities reported by participants in ALTA 1L.
aPer NCI CTCAE v4.03.
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.

Interstitial Lung Disease/Pneumonitis1

  • In the first-line phase 3 trial, ILD/pneumonitis occurred in 5.1% of patients receiving ALUNBRIG, with Grade 3 or 4 reactions occurring in 2.2% of patients1,2

Recommendations for Management1

  • Monitor for new or worsening respiratory symptoms (eg, dyspnea, cough, etc), particularly in the first week of initiating treatment with ALUNBRIG
  • Withhold ALUNBRIG in any patient with new or worsening respiratory symptoms, and promptly evaluate for ILD/pneumonitis or other causes of respiratory symptoms (eg, pulmonary embolism, tumor progression, and infectious pneumonia)
  • For Grade 1-2 adverse reactions, either resume ALUNBRIG with dose reduction as recommended after recovery to baseline or permanently discontinue ALUNBRIG
  • Permanently discontinue ALUNBRIG for Grade 3 or 4 ILD/pneumonitis or recurrence of Grade 1 or 2 ILD/pneumonitis

Dose reductions occurred in 38% of patients receiving ALUNBRIG.1

The most common adverse reactions in ALTA 1L that led to dose reduction were 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%).1

13% of patients permanently discontinued ALUNBRIG due to adverse reactions.1

The most frequent adverse reactions in ALTA 1L that led to discontinuation were ILD/pneumonitis (3.7%) and pneumonia (2.2%).1

Learn about the Safety and Tolerability profile of ALUNBRIG when treating ALK+ mNSCLC patients

Dr. Vijay K. Gunuganti, Oncologist at Texas Oncology, discusses adverse reactions, dose modifications, therapy duration, and the importance of the safety and long-term tolerability profile of ALUNBRIG when treating ALK+ patients in the first line.

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Dr. Vijay K. Gunuganti:

Hi, I’m Dr. Vijay Gunuganti, a practicing medical oncologist, in San Antonio, Texas part of Texas Oncology.

Liz is a 62-year-old woman who recently underwent evaluation after presenting with bloody sputum and productive cough. Other comorbid conditions were anxiety, depression and hypertension, and current medications include an SSRI, beta blocker and thiazide diuretic. A CT scan showed pulmonary nodules and a biopsy revealed non-small cell lung cancer adenocarcinoma. MRI of the brain showed evidence of intracranial metastases. Molecular biomarker testing revealed positive results for anaplastic lymphoma kinase (ALK) rearrangement. Once the diagnosis of stage IV ALK-positive metastatic non-small cell lung cancer was established, Liz was started on first-line therapy with ALUNBRIG 90 mg once daily tablet for 7 days with or without food, then increased to 180 mg tablet once daily. 

After 2 months, CT scans performed to evaluate response to treatment showed stable pulmonary disease. The patient tolerated the treatment well but developed mild to moderate blurred vision. ALUNBRIG was withheld for 5 days with complete resolution of symptoms and then was resumed at a slight dose reduction of 120 mg. She had constipation that was managed with dietary fiber and hydration. Currently Liz has completed a second cycle, tolerating ALUNBRIG 120 mg well with no recurrence of visual symptoms and stable pulmonary and intracranial disease without evidence of progression.

I have treated many patients on ALUNBRIG. I have seen that patients tolerate the treatment well. The results of ALTA 1L demonstrated a median duration of treatment with ALUNBRIG of 24.3 months and a median relative dose intensity of 97%, underscoring the long-term tolerability of ALUNBRIG.1 In addition, for patients receiving ALUNBRIG in ALTA 1L, dose reductions occurred in 38% and permanent discontinuation due to adverse reactions occurred in 13%.1

Because Liz has a medical history of anxiety and depression as well as baseline brain metastases, central nervous system efficacy and minimizing central nervous system effects are an important treatment consideration.2

ALTA-1L was a randomized, open-label, multicenter phase 3 trial designed to assess the efficacy, safety and tolerability of ALUNBRIG compared with crizotinib.1,4 The primary endpoint result of ALTA-1L demonstrated significantly longer median progression-free survival (PFS) of 24.0 months with ALUNBRIG treatment compared with 11.0 months with crizotinib.1 In addition, ALUNBRIG treatment was associated with a significantly higher confirmed overall response rate compared with crizotinib.1 And the ALUNBRIG responses were durable, with a median duration of response that was about 2.5 times longer with ALUNBRIG vs. crizotinib through 40.4 months of median follow-up at the final analysis.1,3

In a post hoc subgroup analysis of patients in ALTA-1L with any brain metastases at baseline, the median PFS was longer with ALUNBRIG treatment vs. crizotinib, with PFS of 24 months for ALUNBRIG vs. 5.6 months for crizotinib.4 Also, the intracranial response rate was three times higher with ALUNBRIG at 78% (14 of 18 patients) vs. 26% (6 of 23 patients) for crizotinib, among patients with measurable brain metastases at baseline in the ALTA-1L study.1 And 64% of responders (9 of 14) achieved an intracranial response duration of 24 or more months with ALUNBRIG treatment in the brain metastases population of the ALTA-1L study; the duration of intracranial response was not estimable for crizotinib.4

Reference List:

  1. ALUNBRIG. Prescribing information. Takeda Pharmaceuticals America, Inc; 2022. 
  2. Guérin A, Sasane M, Zhang J, et al. Brain metastases in patients with ALK+ non-small cell lung cancer: clinical symptoms, treatment patterns and economic burden. J Med Econ. 2015;18(4):312-322. 
  3. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK inhibitor–naive advanced ALK-positive NSCLC: final results of phase 3 ALTA-1L trial. J Thorac Oncol. 2021;16(12):20912108. 
  4. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in advanced ALK inhibitor-naïve ALK-positive non-small cell lung cancer: second interim analysis of the phase III ALTA-1L trial. J Clin Oncol. 2020;38(31):3592-3603.

Dose Modifications

Review recommended dose adjustments for adverse reactions

Patient Brochure

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1L, first-line; ALK, anaplastic lymphoma kinase; ALK+, ALK-positive; CTCAE, Common Terminology Criteria for Adverse Events; ILD, interstitial lung disease; mNSCLC, metastatic NSCLC; NCI, National Cancer Institute; NSCLC, non-small cell lung cancer.