Choose ALUNBRIG^® (brigatinib): Download Helpful Resources for Patients

[Meghan]
Eric and I have been married for about 10 years, we have a pretty vibrant life. 
A lung cancer diagnosis made no sense to us. 
Often people say it's like having the rug pulled out from underneath you, when you get a diagnosis like that. I correct them. And I say it's like the whole floor, coming out from underneath you.
When we got that phone call or news from the physician of his cancer diagnosis, I knew it would be a major inflection point in our life.

[Eric]
Prior to diagnosis, my health started to change in such a way that I was having difficulty breathing. And I was coughing quite a bit.
The symptoms that I had, definitely felt like someone standing on my chest. I was also having difficulty sleeping on my back, which led me to a lot more sleepless nights.
It came up in a conversation with my wife and after she said, “Hey, I'm concerned that your coughing is becoming uncontrollable. I think it's time for you to visit your primary care physician.”
It was a very short period of time, I was able to go from an x-ray to a CT in the same day. And then within two days, I was doing a biopsy.
The first time that I heard the word cancer, from my physician. I will never forget those words.
At age 41. I was diagnosed with stage four ALK positive non-small cell lung cancer. Receiving a diagnosis of this sort, made no sense to me.

[Meghan]
We've obviously subsequently learned that anyone with lungs can get lung cancer.

[Eric]
It took me a while to understand the impact of having brain metastases. And at that point, I was honestly so defeated and downtrodden.
As my treatment options were explained to me, I had the choice of a few different TKIs. I consulted with my family, my oncologists and other primary care specialists to pick the best option for me based on the side effects and the dosing. And for me, that choice was ALUNBRIG.
ALUNBRIG is a prescription medicine used to treat adults with non-small cell lung cancer, NSCLC, that has a certain type of abnormal anaplastic lymphoma kinase, ALK, gene and that has spread to other parts of your body. It is not known if ALUNBRIG is safe and effective in children.
The most important factor when selecting ALUNBRIG was how it would impact my life. And I looked at the side effects and the dosage. And those two combined, made it feel that it would be the least impactful to my everyday life.
I've experienced bradycardia nausea and stomach pain while taking ALUNBRIG. But these are not all of the possible side effects. And everyone is different.
Speak to your healthcare provider about all the potential side effects with ALUNBRIG.

[Meghan]
The treatment was very easy to incorporate into our lives. Being able to take one pill a day was of a significant benefit to him as well.

[Eric]
I started ALUNBRIG on the seven-day starter dosage of 90 milligrams, after which I increased to 180 milligrams, which I currently take.

[Meghan]
From my perspective, Eric has responded really well to ALUNBRIG.
Fortunately, it had a rapid reduction in his tumor volume. He was able to tolerate the medicine.

[Eric]
After reading my scan reports, one of the terms frequently used is “unremarkable”.  That effectively means that while my tumors are still present, they're not growing or spreading. So, I will happily claim to be an “unremarkable cancer patient”.

[Meghan]
When Eric was first diagnosed with lung cancer, he was given a prognosis of nine to 12 months. That timing then aligned with our 10-year wedding anniversary. So, our goal became to make it to the anniversary.
And as we did, we elected to have a vow renewal ceremony with a number of family and friends.
We're able to take less of the focus on his treatment and the worry and put it more so into creating memories together.

[Eric]
The best piece of advice that I've received from my care is that you don't have to hit a homerun your first at bat. You have to get on base. You have to stay healthy enough to take advantage of technology and its advances.
And that's what gives me hope.

[Barbara]
When I do watercolor, I don't think about anything else. I just fall into the painting itself and in this way, I don't have to think about anything negative that's happened in my life. I don't think about my cancer. I don't think about the loss of my husband. I just have a wonderful time relaxing and enjoying the moment.

Hi, I'm Barbara. I was diagnosed with ALK positive metastatic non-small cell lung cancer in 2019. 
In late 2015, I caught a cold. It developed into a very bad cough, which I thought might be pneumonia, so I went to have an X-ray and they discovered that there was something in my lung. They decided to send me for surgery. I had surgery on my right, upper lung and they discovered that it was a malignant tumor.

It was unbelievable that I had lung cancer because I had never smoked a day in my life. I just didn't understand how that was even possible. Most people in my family have passed away from heart-related diseases. Nobody had cancer in my family, so I was doubly shocked that I had cancer, and particularly that it was lung cancer.

They treated me with four rounds of chemotherapy, which seemed to work for a while.

When my cancer came back, I was absolutely devastated.

I underwent four rounds of chemotherapy concurrently with 37 days of radiation. That was to be followed by immunotherapy. Before the immunotherapy started, my oncologist tested my tumor, and that's when I found out that I had the ALK positive mutation.

The fact that I was ALK positive meant that immunotherapy was not going to be called for in my case, and so I guess I was kind of happy that he discovered that I had this mutation, and that was even before I found out that there was a medication that could benefit me.

My doctor mentioned that there was a pill that I would be eligible to take called Alunbrig.

ALUNBRIG is a prescription medicine used to treat adults with non-small cell lung cancer (NSCLC): that has a certain type of abnormal anaplastic lymphoma kinase (ALK) gene, and that has spread to other parts of your body.

It is not known if ALUNBRIG is safe and effective in children.

He said that I would take this once daily in pill form.

When I first started, I was taking 90 milligrams daily. Once I tolerated that, they switched me to 180 milligrams a day, and I've been taking that ever since.

Once I started taking Alunbrig, it just fit so nicely into my lifestyle.

I really like the once daily dosing. I take it in the morning with breakfast and some other medications that I'm taking, and then I don't have to think about it for the rest of the day. That's it.

I have a very active lifestyle. I have loads of hobbies, and I love to travel. Taking one pill once a day works for me.

I have experienced diarrhea, nausea, pains in my legs and hands, as well as changes in the foods I enjoy eating while taking Alunbrig, but these are not all the possible side effects and everyone is different.

Speak to your healthcare provider about all the potential side effects with Alunbrig.

Alunbrig has worked for me, but everyone is different. To anyone living with the same diagnosis, I suggest you speak with your physician to see what would be the best treatment plan for you.

[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.

Kayla Haines, MSN, APRN, FNP-C:

Hi, I’m Kayla Haines, and I work at Florida Cancer Specialists & Research Institute. Today, I’d like to discuss the treatment of metastatic non-small cell lung cancer. 

Non-small cell lung cancer, or NSCLC, is the most common type of lung cancer.

Lung cancer is the leading cause of cancer death worldwide, and the 5-year relative survival rate for metastatic NSCLC is as low as 9%. NSCLC also has a broad molecular profile with several known genetic mutations, also called oncogenic biomarkers, known to cause the disease. Rearrangements in the anaplastic lymphoma kinase, or ALK gene are found in 3%-5% of patients with NSCLC.

ALK-positive NSCLC is more commonly seen in women and younger patients, never or light smokers, and patients with adenocarcinoma histology. 

Patients also tend to be younger, as the median age of diagnosis for ALK-positive NSCLC is 51 years.

ALK rearrangements are usually mutually exclusive with other common biomarkers in NSCLC, such as EGFR and KRAS. 

As with most cases of NSCLC, 5-year survival rates for metastatic disease remain low for ALK-positive patients. ALK-positive metastatic NSCLC can be treated with tyrosine kinase inhibitors, or TKIs, a class of therapy that can deliver positive outcomes to many patients.

Patients with ALK-positive metastatic NSCLC are likely to experience metastases in the brain. Brain metastases affect up to 35% of patients with ALK-positive metastatic NSCLC at the time of diagnosis. These pose many issues for patients, including psychological problems, like depression, anxiety, and cognitive issues as well as symptoms such as headaches and seizures.

Additionally, brain metastases may introduce a financial burden on patients and caregivers, with the average monthly cost per patient almost quadrupling after a diagnosis of brain metastases.

In my experience, I’ve seen that brain metastases can impact patients in a multitude of ways. Frequently I see patients with brain metastases suffer from edema, which often requires treatment with corticosteroids. Dizziness and lack of coordination are also common. More severe symptoms like seizures may also occur, and management often requires an interdisciplinary approach involving neuro-oncologists, neurologists, and neurosurgeons.

Brain metastases may affect a patient’s ability to perform fundamental tasks—how they think, how they walk, and how they take in sensory information. Due to the severity of these symptoms, there’s also a taxing psychological component that comes with a diagnosis of brain metastases. 

Patients become anxious about how brain metastases will impact them in the future, and often question whether they’ll still be able to walk and talk, or if they will experience mood changes over time. The prospect of having a seizure is also extremely daunting for patients and their care teams. This diagnosis alone brings a significant amount of anxiety and fear.

Ultimately, if a treatment option can deliver intracranial efficacy, you may avoid the need to administer additional therapy, like radiation, which can cause cognitive impairment, fatigue, and hair loss. Additionally, by offering an option with intracranial efficacy, you may be able to provide some benefit to patients if their metastases go into remission.

One of the most important things you can do for your patients is to give them the ability to participate in major life milestones, whether that means attending their daughter’s wedding or their grandson’s graduation. Intracranial efficacy may make that possible.

Therefore, given the affinity for ALK-positive metastatic NSCLC to metastasize to the brain, intracranial efficacy is a crucial consideration when determining a treatment. With the advent of ALK TKIs, patient outcomes have improved in recent years. With patients spending more time on therapy, pill burden also becomes an increasingly important consideration when determining a therapy.

High pill burden can negatively impact adherence, and may contribute to poor quality of life. Patients with cancer frequently have comorbid conditions and must often balance multiple complex dosing schedules, resulting in a high pill burden. Additionally, patients may find it challenging to integrate multiple dosing schedules and accommodate the dietary requirements of other treatments, such as with food or on an empty stomach.

From my experience, I’ve seen how important pill burden is, especially for my elderly patients. These patients may have difficulty swallowing or may be on other therapies, so having a low pill burden is important to them. This is also important when it comes to adherence. With an increasing number of required daily pills comes an increasing likelihood of a missed dose. Therefore, prioritizing treatment options with a lower pill burden may help optimize your patient’s treatment journey.

ALK-positive metastatic NSCLC is a unique type of lung cancer affecting a smaller group of patients, and its treatment involves some unique challenges. When making a treatment decision, it’s important to consider clinical aspects like systemic and intracranial efficacy, as well as practical considerations like treatment burden and patient adherence.

I would now like to highlight a treatment option for ALK-positive metastatic NSCLC that may be appropriate for your next eligible patient.

Today, I’d like to discuss ALUNBRIG for the first-line treatment of ALK-positive metastatic NSCLC.

ALUNBRIG is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. 

ALUNBRIG can offer the following key benefits for patients with ALK-positive metastatic NSCLC. Let’s discuss the results of the first-line trial, ALTA 1L. 

ALTA 1L was a Phase 3 trial designed to assess the efficacy, safety, and tolerability of ALUNBRIG for patients with ALK-positive metastatic NSCLC who had not previously received treatment with an ALK inhibitor. Patients were randomized to receive ALUNBRIG 180 mg orally once daily with a 7‐day lead‐in at 90 mg once daily or crizotinib 250 mg orally twice daily. The primary endpoint was PFS according to RECIST v1.1 as evaluated by a Blinded Independent Review Committee, or BIRC. Additional endpoints included BIRC-assessed ORR, DOR, intracranial ORR, and intracranial DOR. Patients with a history of interstitial lung disease, drug‐related pneumonitis, or radiation pneumonitis were excluded from the trial.

ALTA 1L reflected real-world ALK-positive metastatic NSCLC, as patients in the trial exhibited common, real-world characteristics like high rates of adenocarcinoma, presence of brain metastases at baseline, and a preponderance of patients in their 50s. 

Now, let’s take a look at how patients did while receiving ALUNBRIG. 

ALUNBRIG met the primary endpoint of ALTA 1L, doubling the median PFS vs crizotinib in the ITT population. ALUNBRIG lowered the risk of progression or death by 51% vs crizotinib and delivered a median PFS of 24 months vs 11 months with crizotinib. In the ITT population, the median OS was not reached for either arm. Additional OS data are presented here.

ALUNBRIG also demonstrated intracranial efficacy in ALTA 1L. 

In a post hoc subgroup analysis of patients with any brain metastases at baseline, the median PFS was longer with ALUNBRIG vs crizotinib, and the risk of progression or death was reduced by 75%. A post hoc subgroup survival analysis was also conducted in patients with measurable brain metastases at baseline. In these patients, ALUNBRIG reduced the risk of death vs crizotinib by 57%. 

I’ve seen first-hand how intracranial efficacy can impact patients’ lives. For example, when a patient learns that their brain metastases are in remission, it can be like a weight lifted off their shoulders, as they may no longer need to worry about the symptoms associated with brain metastases.

Additionally, in ALTA 1L, ALUNBRIG demonstrated a well-established safety profile. Serious adverse reactions occurred in 33% of patients receiving ALUNBRIG. 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%). 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%).

Please take a moment to review key laboratory abnormalities seen in the ALTA 1L trial.

ALUNBRIG also demonstrated long-term tolerability in ALTA 1L, which is an important consideration in a treatment setting where patients frequently receive long-term therapy. 

The median duration of treatment with ALUNBRIG was 24.3 months and the median relative dose intensity was 97%. Permanent discontinuation due to adverse reactions occurred in 13% of patients receiving ALUNBRIG. Furthermore, patients who took ALUNBRIG reported better quality of life as measured by delayed median time to worsening in the Global Health Score/Quality of Life scale. There were several study limitations. These patient-reported outcome endpoints were exploratory and not prespecified. The improvement in QoL scores and delay in worsening of GHS/QoL may be an overestimation, because patients were not blinded to treatment assignment. These differences in global QoL could reflect differences in efficacy on disease-related symptoms and in treatment-related adverse events.

Quality of life is crucial, especially for younger patients with metastatic disease who require long-term therapy. Quality of life is important because metastatic NSCLC is a life-long disease. We want to make sure patients are living the best life that they can. Additionally, many of our patients want to avoid the psychological component of feeling sick and having to go to the clinic for IV infusions. The ability to offer patients as few pills a day as possible can make a positive difference in their lives. This offers a fitting transition in our discussion to the dosing and administration of ALUNBRIG.

Dosing with ALUNBRIG is simple, and can be worked into your patients’ schedules with ease. The recommended dosage of ALUNBRIG is 1 tablet, once daily. It can be taken at any time of the day either with or without food.

Once-daily dosing can substantially reduce a patient’s pill burden. Consider, for example, the yearly number of pills a patient may take under more complex dosing schedules, such as those involving 2 or 4 pills daily. The dosage of ALUNBRIG is 90 mg once daily for the first 7 days. This dosage is then increased to 180 mg once daily and administered until disease progression or unacceptable toxicity occurs.

In my experience of treating ALK-positive metastatic NSCLC, I’ve seen that 1-tablet, once-daily dosing provides patients with a convenient option. The 90-mg and 180-mg doses each involve just 1 pill per day, making it easier to change the dosage if we need to, and for patients to adhere to their prescribed dosing schedule. 

Patients can start treatment with the help of the ALUNBRIG Initiation Pack, which conveniently provides the first month’s tablets. The instructions are clear and detailed, helping to reinforce a patient’s knowledge on how to properly start therapy.

As we’ve seen, when you choose ALUNBRIG for first-line ALK-positive metastatic NSCLC, you can offer systemic efficacy, efficacy in patients with brain metastases at baseline, tolerability over long-term treatment, and simple, once-daily dosing, which can help alleviate pill burden. 

In the ALK-positive setting, the ability to offer an option with strong intracranial efficacy can make a real impact on patients’ lives.

As an experienced clinician, I know how brain metastases can take a toll on patients. I’ve seen the pain they cause, as well as the effects on behavior and mood. I also know what intracranial efficacy can mean for patients. Remission of brain metastases can offer cathartic relief, giving cause for celebration. You may offer your next patient that same chance for systemic and intracranial efficacy, and it’s available as a once-daily oral therapy that is easy for patients to take, and tolerable over the long term.

I hope that you will consider first-line ALUNBRIG for your next patient with ALK-positive metastatic NSCLC.
 

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.

Annotations:
^† 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.org. 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. https://www.globenewswire.com/news-release/2023/03/01/2618622/0/en/Cancer-Biological-Therapy-Market-Size-to-Reach-USD-213-6-BN-by-2032.html 
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.
    

Dr. Vijay K. Gunuganti:

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

Carl is a 50-year-old Hispanic male, factory sales representative, never-smoker, with a history of diabetes, hypertension and obesity. He recently developed a pleural effusion associated with a 6-cm left lower lobe mass and analysis of the fluid showed non-small cell lung cancer. MRI of the brain identified multiple small focal lesions consistent with metastatic lung cancer, although he was asymptomatic. Molecular biomarker testing revealed positive results for anaplastic lymphoma kinase (ALK) rearrangement. The rest of the biomarker testing was negative. PD-L1 expression was 70%. Carl was diagnosed with stage IV ALK-positive non-small cell lung cancer and started on first-line therapy with ALUNBRIG 90 mg once daily tablet for 7 days with or without food, then the dose was increased to 180 mg tablet once daily.

After two cycles of treatment, Carl had a reduction in the size of the pulmonary mass. At cycle 4, he had a considerable reduction in the pulmonary mass with a complete intracranial response based on an MRI scan. Overall, he tolerated the treatment well. However, he did have an episode of grade 3 hypertension at week 2 while taking the 180 mg dose of ALUNBRIG, despite coadministration of two antihypertensive agents. ALUNBRIG was temporarily withheld, dietary changes were suggested, and home monitoring of blood pressure was arranged. Blood pressure normalized and ALUNBRIG was resumed at the usual dose without incident. Currently, after six cycles of treatment, Carl remains on ALUNBRIG 180 mg with stable partial systemic response, complete intracranial response, and a good blood pressure control. 

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.

Carl's treatment plan with ALUNBRIG needs to include appropriate monitoring of his comorbid conditions of diabetes, obesity, and hypertension. In ALTA-1L, grade 3 episodes of hypertension occurred in 13% of participants and grade 3 hyperglycemia in 7.5% of participants.¹ Periodic assessment of blood pressure and fasting glucose are recommended with ALUNBRIG therapy.¹

Drug-drug interactions are important to consider. We need to look at all the medications patients are taking to assess for potential interactions that can impact ALUNBRIG efficacy and manage patients accordingly. Some medications, such as CYP3A inducers, can decrease the efficacy or concentration of ALUNBRIG.¹ Alternatively, CYP3A inhibitors can increase the concentration of ALUNBRIG.¹ Usually, I defer to my pharmacist to ensure that we go through each drug-drug interaction before I prescribe ALUNBRIG.

When considering dosage adjustments, it is important to note that in ALTA-1L, 13% of patients permanently discontinued ALUNBRIG for adverse reactions, and 38% of patients required a dose reduction due to adverse reactions.¹ Dose adjustments of ALUNBRIG are recommended in the case of systolic blood pressure ≥160 mm HG or diastolic blood pressure ≥100 mm Hg, or blood sugar >250 mg/dL.¹

Reference List:

1. ALUNBRIG. Prescribing information. Takeda Pharmaceuticals America, Inc; 2022. 
2. Drugs.com. Drug interactions between ALUNBRIG and atorvastatin. Updated January 2023. Accessed January 15, 2023. https://www.drugs.com/interactionscheck.php?drug_list=380618473,276- 0&types%5B%5D=major&types%5B%5D=minor&types%5B%5D=moderate&types%5B%5D=food &types%5B%5D=therapeutic_duplication 
3. Takeda Pharmaceuticals U.S.A., Inc. Data on file; 20USO-BRG-0647 5/23

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.