Patient-Reported Quality of Life with ALUNBRIG^® (brigatinib)

Dr. Vijay K. Gunuganti:

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

Jim is a 49-year-old Asian male construction worker, never-smoker, without significant medical history or family history of cancer. He was diagnosed with stage IV metastatic non-small cell lung cancer. PD-L1 expression was 50%. MRI of the brain showed no evidence of brain metastases. The patient was found to have anaplastic lymphoma kinase (ALK)-positive disease. The rest of the oncogenic driver mutations, such as EGFR, KRAS and ROS1, were negative. Jim’s Asian ethnicity is well-represented in the ALTA-1L trial, since more than 40% of the participants treated with ALUNBRIG were of Asian descent, as were 36% of patients treated with crizotinib.¹ 

After his diagnosis, Jim began 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. Just 2 months after starting treatment, he had a good reduction in the size of the pulmonary and liver masses. After 2 years of treatment and 24 cycles of ALUNBRIG, Jim had a sustained pulmonary response. At 28 months, there was minimal CT evidence of any previous mass. 

One of the adverse events he had was grade 1 elevation of aspartate aminotransferase (AST) at 2 months of treatment that was resolved after 4 months of treatment without any dose reduction. He experienced some mild fatigue and nausea and a little bit of photosensitivity with occupational sun exposure since he's a construction worker. Otherwise, he tolerated the treatment well. 

In the ALTA 1L clinical trial, serious adverse reactions occurred in 33% of patients receiving Alunbrig. The most common serious ARs 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.

While results vary among patients, Jim just completed 30 cycles of ALUNBRIG 180 mg, and he currently has a complete pulmonary response based on CT scans that are performed every 4 months. Annual MRI follow-up studies have not revealed intracranial metastatic disease.

Jim is a good candidate for ALUNBRIG for the following reasons: he has been diagnosed with ALK+ disease but he is also young with an active lifestyle. Patients, like Jim, with an active lifestyle and desire to continue working, need effective treatment with a dosing regimen that fits their lifestyle. When looking at medications, we always look at efficacy, safety and tolerability. For me, efficacy is an important factor. ALUNBRIG is efficacious, for both systemic and intracranial disease.² ALTA-1L showed that ALUNBRIG was associated with a doubled median progression-free survival of about 24 months vs. 11 months, a higher confirmed overall response rate and about 2.5 times longer median duration of response vs. crizotinib.²

Quality of life is important for patients with stage IV non-small cell lung cancer. Treatment with next-generation ALK inhibitors is often prolonged, especially for younger patients,³ so the effects of treatment on health-related quality of life may be particularly important. These patient-reported outcome endpoints in ALTA-1L trial were exploratory and not prespecified. The improvement in QoL scores and delay in worsening of GHS/ quality of life may be an overestimation, because patients were not blinded to treatment assignment. And ALTA-1L showed that patients taking ALUNBRIG reported better quality of life compared to crizotinib across multiple functional and symptom scales.^4,5

Hepatotoxicity can occur with ALUNBRIG.² That's why we keep monitoring the liver enzymes in these patients, especially for the first several months, as well as throughout treatment. If you see an increase in terms of grade 3 or grade 4 toxicity without significant elevation of bilirubin, then we must hold the drug. If the patient experiences grade 4 toxicity and the bilirubin is elevated in the absence of cholestasis or hemolysis, then we must discontinue it.²

Reference List:

1. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018;379(21):2027-2039. 
2. ALUNBRIG. Prescribing information. Takeda Pharmaceuticals America, Inc; 2022.
3. Pacheco JM, Gao D, Smith D, et al. Natural history and factors associated with overall survival in Stage IV ALK-rearranged non-small cell lung cancer. J Thorac Oncol. 2019;14(4):691-700. 
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.