For the Treatment of ALK+ mNSCLC 
Choose ALUNBRIG^® (brigatinib) 
for first-line (1L) efficacy and 
long-term tolerability^1,2,a

[Dr. Mohammad Jahanzeb]

My name is Mohammad Jahanzeb. I started practicing oncology more than 30 years ago. Back then, there were no targeted approved drugs for use in lung cancer. We now have a wider range of drugs, including those dedicated to targeting actionable mutations.

For decades, the average survival for a patient with stage IV NSCLC without treatment was only a few months from diagnosis. Now in 2024, thanks to advancements in the treatment landscape, we’re measuring survival rates in years instead of months.

To me, the most important consideration when treating patients with ALK-positive NSCLC of course is efficacy of the treatment, followed by its side effect profile, and lastly, its convenience or ease of administration.

In my experience, quality of life is of paramount importance in these patients. The length of survival makes it imperative that they lead as normal a life as possible for their remaining time, especially in first-line treatment. They want to be able to continue with their jobs as well as activities of daily living and take care of their dependent children. It is wonderful when patients are able to work full-time, as a majority of them are relatively young, with a median age that's younger by about two decades compared with other lung cancer patients. From my experience, when patients receive a diagnosis, they want the most effective and least toxic therapy for themselves.

Brain metastasis can be very symptomatic in patients and often leads to complications, including changes in behavior and personality. It is not uncommon for these patients to present to the emergency room with a seizure or a stroke. At that point, it becomes apparent upon brain imaging that there is a tumor or multiple lesions in the brain and the primary tumor is uncovered with subsequent imaging. A cerebrovascular accident could lead to weakness or paralysis of different parts of the body as well as speech impairments and cognitive deficiencies. That is why prompt discovery of and intervention for brain metastases remain very important.

About 35% of patients present with brain metastases and up to 75% will develop metastatic disease in the brain over the course of their illness. I find it is very important to start with agents that penetrate the central nervous system whether a patient has brain metastases or not. In my experience, patients without brain metastases tend to have better outcomes than those with brain metastases.

Although only 3% to 7% of patients with NSCLC harbor rearrangement of the ALK gene in their tumors, my specialized interest in lung cancer has allowed me to see quite a few ALK-positive patients in my practice. I also participated in the ALTA1 randomized trial, which compared ALUNBRIG (also known as brigatinib) with crizotinib in the first-line setting.

I have seen great results overall in many of my patients with ALUNBRIG, as the efficacy is strong and responses are durable. The BIRC assessment showed 24 months of median progression-free survival with ALUNBRIG versus 11.1 months with crizotinib, while the investigator assessment demonstrated 30.8 months versus 9.2 months, respectively.

I have a patient who was diagnosed with ALK-positive metastatic NSCLC in 2019 after her initial stage II NSCLC recurred. This patient was 68 years old and retired at the time. She had never smoked; had no family history of cancer; and had an active lifestyle, enjoying long walks, traveling, and painting. Upon learning of her ALK-positive diagnosis, her goals were to remain active, self-sufficient, and to spend time with her family. She also expressed a preference for an oral treatment with a manageable safety profile and convenient dosing in order to maintain her quality of life.

My strong preference for this patient’s first-line therapy was ALUNBRIG based on her goals, her progressive disease, and my own experiences. I wanted to give her something effective, and I knew that it could potentially delay intracranial progression. In the ALTA-1L study, patients taking ALUNBRIG, regardless of whether they had brain metastases, saw 44.1 months of median intracranial progression-free survival, while patients in the crizotinib group experienced 21.2 months.

I was familiar with ALUNBRIG and comfortable with it.

Prior to beginning therapy, my patient’s PET scans revealed lymphadenopathy and metastases below the diaphragm. I initiated ALUNBRIG at 90 mg once daily and escalated her dose to 180 mg once daily after 7 days to achieve the optimal dose with manageable side effects.

I ordered follow-up PET scans 2 months after ALUNBRIG initiation and every 3 months subsequently until 2 years, every 4 months subsequently until 4 years, then every 6 months. I also ordered an MRI of the brain every 6 months to monitor her disease.

This patient experienced impressive results with ALUNBRIG, including a rapid response and stable disease, and has remained on therapy since 2019. Her PET scans have shown improvement and her tumors have shrunk.

My selection of ALUNBRIG for this patient would have remained the same if she had presented with brain metastases at diagnosis. This is supported by the ALTA-1L study, which showed longer lasting intracranial responses versus crizotinib in patients with any brain metastases. Patients with brain metastases at baseline taking ALUNBRIG had a median intracranial progression-free survival of 24 months versus 5.5 months. Intracranial complete response rates in this population were also higher at 45% with ALUNBRIG versus 2% with crizotinib.

My selection was also supported by the overall survival results from ALTA-1L. In the ITT population, median OS was not reached for either arm; however, longer OS was seen in patients with measurable brain metastases versus crizotinib.

In my experience, ALUNBRIG has shown effective CNS penetration, thereby potentially saving patients from the prospect of whole brain irradiation or even Gamma Knife radiosurgery in many cases. Many of my patients have been able to continue their active lifestyle without a significant decrease in their quality of life. I have seen responses quickly, usually at the first radiographic evaluation after 2 months of treatment. However, many of my patients have told me that they notice symptomatic improvement a lot sooner than that.

Although individual experiences may differ, my patient has experienced some GI toxicity, nausea, and diarrhea, which were managed through dietary changes. She did not require any dose reductions, and she has been able to retain her quality of life and active lifestyle.

In terms of adverse events, I usually educate my patients thoroughly about the prospect of early-onset pneumonitis and have our nurses call them multiple times during the first week of treatment. In the rare occurrence of this complication, it is necessary to institute treatment with high doses of steroids promptly and then taper steroids gradually, while withholding ALUNBRIG until recovery.

Other common side effects include gastrointestinal events, increased blood CPK, cough, and increased aminotransferases. Based on my personal experiences, none of my patients on ALUNBRIG have experienced early-onset pneumonitis. I typically start them on the initiation pack to reduce the probability for this type of AE. Some of my patients have had minor nausea and diarrhea or blood pressure elevations, which are easily managed. I have had many patients take ALUNBRIG and have not had to discontinue it because of poor tolerance.

Treatment dosing definitely influences my choice of therapy, because many of these patients are on these pills for many years. I find that my patients prefer once-daily dosing, as many of them are on other medications and supplements.

When my patients are first diagnosed with ALK-positive metastatic NSCLC, they typically express shock. Ideally, they want to be cured, but that’s not possible with stage IV disease. That is perhaps the most difficult reality to impress upon them even after they have received the good news that, due to the availability of numerous targeted treatment options, like ALUNBRIG, they may potentially live longer than their counterparts with other forms of lung cancer that lack targeted treatment options.

Overall, I consider ALUNBRIG to be a great option for the first-line treatment of ALK-positive mNSCLC because of its strong systemic and intracranial efficacy and tolerability profile.