Choose ALUNBRIG® (brigatinib) for Proven First-Line CNS Efficacy1

In an ALTA 1L study post hoc subgroup analysis of patients with brain mets at baseline, ALUNBRIG demonstrated durable intracranial responses and extended mPFS vs crizotinib.1,2

ALUNBRIG delivered durable intracranial response1,2

Confirmed Intracranial Overall Response Rates:
Patients with Measurablea Brain Metastases at Baseline1,2

Visualization of intracranial overall response rates, including PR and CR with ALUNBRIG® and PR with crizotinib.
  • In patients with any brain metastases at baseline, ALUNBRIG demonstrated 45% complete intracranial response (n=21/47) vs 4% (n=2/49) with crizotinib2

Study Limitation: ALTA 1L was not powered to detect differences across subgroups.

Brain metastases populationa (post hoc subgroup analysis)

75% Reduction in Risk of Progression or Death vs Crizotinib2,3

Systemic BIRC-assessed PFS in patients with any brain metastases at baseline2,3

Graph of PFS in patients with any brain metastases at baseline. The median PFS with ALUNBRIG® was 24 months, the median PFS with crizotinib was 5.6 months.
  • The INV-assessed median PFS was not reached with ALUNBRIG (95% CI: 18.4, NR) vs 5.9 months (95% CI: 3.7, 7.5) with crizotinib2

Study Limitation: ALTA 1L was not powered to detect differences across subgroups.

ITT population (final analysis with 40.4 months of median follow-up)

ALUNBRIG demonstrated durable intracranial PFS of ~4 years4

Intracranial PFS in the ITT population

Intracranial PFS in the ITT population. Median intracranial PFS with ALUNBRIG® was 44.1 months vs 21.2 months with crizotinib.
  • 3-year intracranial PFS probability in the ITT population (BIRC-assessed): 56% for ALUNBRIG (n=137) vs 38% for crizotinib (n=138)4 
  • In patients with any brain metastases at baseline, the median intracranial PFS was 24.0 months (95% CI: 12.9, 30.8) with ALUNBRIG vs 5.5 months (95% CI: 3.7, 7.5) with crizotinib4 

Intracranial PFS was not part of the statistical testing hierarchy. The clinical relevance of these data is unknown, as only brain lesions were reviewed. Patients were counted as having an event if there was radiologic progression, radiotherapy to the brain, or death.

Study Limitation: ALTA 1L was not powered to detect differences across subgroups; results are presented descriptively.

Brain metastases populationa (post hoc subgroup analysis)

57% Reduction in the Risk of Death vs Crizotinib4

OS in Patients with Measurable Brain Metastases at Baseline4

Graph of OS in patients with any brain metastases at baseline, comparing ALUNBRIG® and crizotinib.

Study Limitation: ALTA 1L was not powered to detect differences across subgroups.

  • The 4-year KM-estimated OS rate was 71% (95% CI: 53%, 84%) with ALUNBRIG vs 44% (95% CI: 28%, 59%) with crizotinib4

Discover how first-line ALUNBRIG could treat a hypothetical ALK+ patient with brain mets at baseline

Dr. Vijay K. Gunuganti, an Oncologist at Texas Oncology, discusses patient evaluation, the significance of biomarkers and brain mets, and using ALUNBRIG as a 1L treatment option for ALK+ mNSCLC.

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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.

Cindy is a 43-year-old white female preschool teacher, never-smoker, without significant medical history or family history of cancer. She was diagnosed with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer with asymptomatic brain metastases. ALUNBRIG was initiated at 90 mg once daily tablet for 7 days with or without food, and increased to 180 mg tablet once daily per the recommended/approved dosing. After 2 months of treatment, she had partial systemic and intracranial responses, based on the CT scans of the chest, abdomen; and pelvis and MRI of the brain. She experienced a few manageable adverse events that included grade 1 rash on the lower face that was treated with topical steroid cream. She also experienced light hair thinning and a mild increase in creatine phosphokinase. Otherwise, her treatment was well-tolerated. After completion of 24 cycles, almost 2 years after initiation of ALUNBRIG 180 mg tablets, Cindy remained on treatment with good tolerability. She had a sustained systemic response with further decrease in the tumors in the chest and a complete intracranial response.

I'd like to highlight that not all patients are alike and other patients sometimes may experience other side effects. In the ALTA 1L clinical trial, serious adverse reactions occurred in 33% of patients receiving Alunbrig. The most common adverse reactions were pneumonia, ILD/pneumonitis, pyrexia, dyspnea, pulmonary embolism, and asthenia. Fatal ARs occurred in 2.9% of patients and included pneumonia, cerebrovascular accident, and multiple organ dysfunction syndrome. 

Please see additional safety information of ALUNBRIG at the end of this video.

Initially when I see a patient with lung cancer, I conduct testing for the mutations recommended by the National Comprehensive Cancer Network (NCCN), including analysis for mutations or alterations in EGFR, ALK, KRAS, ROS1, BRAF, NTRK1/2/3, METex14 skipping, RET, ERBB2 (HER2) and PD-L1.1†‡ I know that it may be difficult to conduct biomarker testing due to a paucity of tissue, but I try hard to get at least these targetable mutations. I conduct next-generation sequencing that encompasses all of these. In the meantime, I also perform a liquid biopsy if I do not have sufficient tissue to make sure that we do not miss anything.

It is very important to conduct biomarker testing.1†‡ In 2022, the oral segment accounted for about 60% of the cancer biological therapy market and many of these oral agents are targeted therapies.2 Now that efficacious oncologic treatments that target specific tumor mutations or biomarkers are available, biomarker testing results help guide my treatment selection. However, physicians who are not testing for all of the NCCN recommended biomarkers may not be aware of such guideposts. Identification of Cindy’s ALK+ status for her metastatic non-small cell lung cancer tumor indicated that she could benefit from an ALK inhibitor.1†‡

In my experience, ALUNBRIG is well-tolerated and has good intracranial response, which I have seen in many of my patients and will discuss later. In ALTA-1L, the median duration of treatment with ALUNBRIG was 24.3 months with a median relative dose intensity of 97%, supporting that it’s well tolerated.3 That's why I feel ALUNBRIG was the choice for her.

Intracranial disease is very important to control in addition to systemic disease. Patients who had baseline brain mets achieved better responses with ALUNBRIG vs crizotinib. If you look at the intracranial responses that were seen in the ALTA-1L trial that compared ALUNBRIG with crizotinib. 78% of patients that is, 14 out of 18, treated with ALUNBRIG had a confirmed intracranial response compared with 26% of patients or 6 out of 23 treated with crizotinib, demonstrating an intracranial response rate three times higher with ALUNBRIG. In the ALUNBRIG group, 28% of patients or, 5 out of 18, had a complete response compared with no patients in the crizotinib group. And 64% of responders or, 9 out of 14, in the ALUNBRIG group had a confirmed intracranial response of 24 months or longer, while the duration of intracranial response was not estimable for crizotinib.3 In addition, the median progression free survival for patients with brain metastases at baseline was longer with ALUNBRIG at 24 months compared with 5.6 months for crizotinib.4

In my opinion, Cindy is a strong candidate for ALUNBRIG as she has ALK+ mNSCLC disease, which means we should be using a targeted approach. Second, she has asymptomatic brain metastases, so we want an ALK TKI with good intracranial efficacy, which narrows options down. ALUNBRIG is one of those options.

The NCCN Guidelines® for NSCLC provide recommendations for individual biomarkers that should be tested and recommend testing techniques, but do not endorse any specific commercially available biomarker assays or commercial laboratories.See the NCCN Guidelines for detailed recommendations, including other preferred treatment options.

Reference List:

  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.3. 2023. © National Comprehensive Cancer Network, Inc. All rights reserved. Accessed March 13, 2023. To view the most recent and complete version of the guideline, go online to NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 
  2. Precedence Research. Cancer biological therapy market size to reach USD 213.6 bn by 2032. March 01, 2023. Accessed March 09, 2023. 
  3. ALUNBRIG. Prescribing information. Takeda Pharmaceuticals America, Inc; 2022. 
  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. 
  5. Takeda Pharmaceuticals U.S.A., Inc. Data on file.

Quality of Life

Explore how ALUNBRIG may impact a patient's quality of life

aPatients with brain metastases ≥10 mm in longest diameter at baseline.
bDuration of intracranial response was measured from date of first intracranial response until intracranial disease progression (new lesions, intracranial target lesion diameter growth ≥20% from nadir, or unequivocal progression of intracranial nontarget lesions) or death.

BIRC, blinded independent review committee; CI, confidence interval; CNS, central nervous system; CR, complete response; DOR, duration of response; HR, hazard ratio; INV, investigator; ITT, intent-to-treat; KM, Kaplan- Meier; mPFS, median PFS; NE, not estimable; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response.