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

Dr. Albino:

Hello, I am Dr. Miguel Albino, an oncologist at Texas Oncology. Today I will be discussing a first-line treatment option for patients with ALK+ mNSCLC with brain metastases.

For patients with ALK+ mNSCLC, quantity of life is increasing,^1-3 and QoL is also increasingly important. With survival outcomes improving in NSCLC, patients spend more time on therapy.³

It is important to note that more time on therapy increases the importance of treatment efficacy in the brain due to brain metastases,^1,4 long-term tolerability,³ and reduced pill burden.⁵

Because tumor types and treatment approaches can vary, I always perform comprehensive genomic testing to determine whether there is an actionable mutation. This helps guide my treatment recommendations. Next, I will discuss the clinical and safety data for ALUNBRIG^® (brigatinib), a treatment option for ALK+ mNSCLC.

ALUNBRIG is a kinase inhibitor 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.

Based on clinical data, the National Comprehensive Cancer Network^® (NCCN^®) recommends brigatinib as a Category 1 preferred first-line treatment option for ALK+ mNSCLC.^6,a,b,c Before I discuss the clinical data for ALUNBRIG, I would like to review the Warnings and Precautions.

Voiceover:

WARNINGS AND PRECAUTIONS: Interstitial Lung Disease (ILD)/Pneumonitis: Monitor for new or worsening respiratory symptoms, particularly during the first week of treatment. Withhold ALUNBRIG for new or worsening respiratory symptoms and promptly evaluate for ILD/pneumonitis. Upon recovery, either dose reduce or permanently discontinue ALUNBRIG. 

Hypertension: Monitor blood pressure after 2 weeks and then at least monthly during treatment. For severe hypertension, withhold ALUNBRIG, then dose reduce or permanently discontinue. 

Bradycardia: Monitor heart rate and blood pressure regularly during treatment. If symptomatic, withhold ALUNBRIG, then dose reduce or permanently discontinue. 

Visual Disturbance: Advise patients to report visual symptoms. Withhold ALUNBRIG and obtain ophthalmologic evaluation, then dose reduce or permanently discontinue ALUNBRIG. 

Creatine Phosphokinase (CPK) Elevation: Monitor CPK levels regularly during treatment. Based on the severity and with muscle pain or weakness, withhold ALUNBRIG, then resume or reduce dose.

Hepatotoxicity: Monitor alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin levels regularly during treatment. Based on severity, withhold dose, then resume at lower level. 

Pancreatic Enzyme Elevation: Monitor lipase and amylase levels regularly during treatment. Based on the severity, withhold ALUNBRIG, then resume or reduce dose. 

Hyperglycemia: Assess fasting serum glucose prior to starting ALUNBRIG and regularly during treatment. If not adequately controlled with optimal medical management, withhold ALUNBRIG, then consider dose reduction or permanently discontinue, based on severity. 

Photosensitivity: Advise patients to limit sun exposure. Based on severity withhold ALUNBRIG, then resume at the same dose, reduce the dose, or permanently discontinue. 

Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. 

Please see more information about each Warning and Precaution, along with additional Important Safety Information later in this presentation.

Dr. Albino:

Now, let’s take a look at the clinical trial that evaluated the efficacy, safety, and tolerability of ALUNBRIG.

ALTA 1L was a phase 3, randomized, open-label, multicenter trial in adult patients with locally advanced or metastatic ALK+ NSCLC who had not previously received an ALK-targeted therapy.^7,8 Eligible patients were allowed to have up to one prior regimen of chemotherapy.⁸ 

A total of 275 patients were randomized 1 to 1 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.⁸ 

Patients were stratified by the presence or absence of CNS metastases at baseline and by prior chemotherapy in the locally advanced or metastatic setting.⁸ 
It is important to note that crossover from ALUNBRIG was permitted after disease progression.⁸ 

The major efficacy outcome measure was PFS according to RECIST v1.1. Additional efficacy outcome measures included confirmed ORR, DOR, intracranial ORR, and intracranial DOR.⁸

At the time of the second interim analysis, the data cutoff was 22 months after the last patient was enrolled, with a median follow-up of 24.9 months for ALUNBRIG and 15.2 months for crizotinib.^7,9 The final analysis was conducted at a median follow-up of 40.4 months, and select efficacy data from the final analysis is included in this presentation.¹⁰

Patients in the ALTA 1L trial exhibited characteristics that were common among real-world patients with ALK+ mNSCLC. This included high rates of adenocarcinoma, a presence of brain metastases at baseline, and a median age of 59. Demographics and baseline factors were balanced between the treatment arms.¹¹

ALUNBRIG doubled the median PFS versus crizotinib in the ITT population. In the ALUNBRIG arm, the BIRC-assessed median PFS was 24 months versus 11 months in the crizotinib arm. Additionally, ALUNBRIG exhibited a 51% reduction in the risk of progression or death.⁸ The investigator-assessed median PFS was 29.4 months for ALUNBRIG versus 9.2 months for crizotinib.⁷

Additionally, high response rates and durable responses were seen with ALUNBRIG in the ITT population. ORR was 74% for ALUNBRIG compared with 62% for crizotinib. Fifteen percent of patients in the ALUNBRIG arm achieved a CR versus 9% in the crizotinib arm.⁸ 

At the final analysis, with 40.4 months of median follow-up, the median DOR was approximately 2.5 times longer with ALUNBRIG (at 33.1 months) than with crizotinib (13.8 months).^8,1

In a post-hoc subgroup analysis of patients with brain metastases at baseline, the median PFS was longer with ALUNBRIG versus crizotinib. The median PFS for patients was 24 months with ALUNBRIG versus 5.6 months with crizotinib. The hazard ratio for disease progression or death in patients with brain metastases at baseline was 0.25. This corresponds to a 75% reduction in risk of progression in patients treated with ALUNBRIG compared with crizotinib.^7,9 ALTA 1L was not powered to detect differences across subgroups.

In the patients with measurable brain metastases at baseline, the intracranial response rate was 3 times higher with ALUNBRIG versus crizotinib. Seventy-eight percent of patients treated with ALUNBRIG had a confirmed intracranial ORR compared with 26% of patients treated with crizotinib. Furthermore, 28% of patients in the ALUNBRIG arm had a CR compared with no patients in the crizotinib arm. ⁸ 

Additionally, 64% of responders achieved an intracranial response duration greater than or equal to 24 months with ALUNBRIG.⁸

In the final analysis of patients in the ITT population, intracranial PFS with ALUNBRIG was 44.1 months vs 21.2 months with crizotinib with a hazard ratio of 0.44. The 3-year intracranial PFS probability in the ITT population was 56% for ALUNBRIG and 38% for crizotinib.¹⁰ 

The secondary endpoint of intracranial PFS was not part of the statistical testing hierarchy. In addition, the clinical relevance of these data is unknown because they do not include disease status in the rest of the body; only brain lesions were reviewed. Patients were counted as having an event if there was radiologic progression, radiotherapy to the brain, or death. ALTA 1L was not powered to detect differences across subgroups; results are presented descriptively.

Intracranial PFS was defined as the time interval from the date of randomization until the first date at which CNS disease progression was objectively documented or death due to any cause, whichever occurred first.¹¹ 

In the final analysis of patients in the brain metastasis population, intracranial PFS with ALUNBRIG was 24.0 months vs 5.5 months with crizotinib with a hazard ratio of 0.29. The 3-year intracranial PFS probability in this population was 31% for ALUNBRIG and 9% for crizotinib.10 The hazard ratio for intracranial PFS in patients who did not have brain metastases at baseline was 0.703.⁹

OS was also assessed in all patients, including those with brain metastases at baseline. In the ITT population, the median OS was not reached for both arms8 —30% of patients in the ALUNBRIG arm expired versus 37% of patients in the crizotinib arm.^8,10 

The 3-year OS rate was 71% with ALUNBRIG and 68% with crizotinib. Forty-seven percent of patients in the crizotinib arm had crossed over to receive ALUNBRIG.¹⁰

In a post-hoc subgroup analysis of patients with measurable brain metastases at baseline, ALUNBRIG reduced the risk of death by 57% versus crizotinib, which corresponds to the hazard ratio of 0.43.¹⁰ As a reminder, this study was not powered to detect differences across subgroups.

Patients taking ALUNBRIG also reported better QoL compared with crizotinib. As a secondary endpoint, ALUNBRIG delayed time to worsening in GHS/QoL compared with crizotinib.⁷ 

Median time to worsening GHS/QoL was 26.7 months in the ALUNBRIG arm compared with 8.3 months in the crizotinib arm.⁷ The time to worsening was assessed by physical, emotional, cognitive, and social functioning scales as well as improvement of disease symptoms.⁹ 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. Among responders, the median duration of improvement in QoL had not been reached for ALUNBRIG versus 12 months for crizotinib.⁷

Next, let’s talk about the safety profile for ALUNBRIG. ALUNBRIG has a well-established safety profile.8 Serious ARs occurred in 33% of patients receiving ALUNBRIG. 

The most common serious ARs in ALTA 1L were pneumonia (at 4.4%), ILD/pneumonitis (3.7%), pyrexia (2.9%), dyspnea (2.2%), pulmonary embolism (2.2%), and asthenia (2.2%). Fatal ARs occurred in 2.9% of patients and included pneumonia (at 1.5%), cerebrovascular accident (at 0.7%), and multiple organ dysfunction syndrome (also at 0.7%).⁸

The table here shows ARs in greater than or equal to 10% for all grades or greater than or equal to 2% for grades 3 to 4 of patients by arm in ALTA 1L.⁸ 

ALUNBRIG was also well tolerated long-term, based on the median follow-up of 40.4 months in the ALUNBRIG arm of ALTA 1L.10 The median duration of treatment with ALUNBRIG was 24.3 months, with a median relative dose intensity of 97%.⁸ 

Dose reductions occurred in 38% of patients receiving ALUNBRIG. The most common ARs in ALTA 1L that led to dose reduction were increased creatinine phosphokinase (15%), increased lipase (6.6%), increased amylase (4.4%), increased aspartate aminotransferase (2.2%), ILD/pneumonitis (2.2%), and hypertension (at 2.2%).⁸

Permanent discontinuation due to ARs occurred in 13% of patients receiving ALUNBRIG.The most frequent ARs in ALTA 1L that led to discontinuation were ILD/pneumonitis (3.7%) and pneumonia (at 2.2%).⁸

This table shows the laboratory abnormalities greater than or equal to 20% (all grades) in patients by arm in ALTA 1L, with increased CPK and lipase being the most common grades 3 to 4 abnormalities.⁸

As I touched on earlier, high pill burden can negatively impact adherence and may contribute to poor quality of life.

The dosing for ALUNBRIG is 1 tablet once daily, with or without food. Once-daily dosing can substantially reduce a patient’s pill burden.⁸ For more detailed dosing information, please refer to the Prescribing Information for ALUNBRIG, available above this video.

In summary, consider ALUNBRIG as a first-line treatment option for patients with ALK+ metastatic NSCLC, as it offers systemic and brain mets efficacy, long-term tolerability, and once-daily dosing.⁸ 

Now please listen to the Important Safety Information.

Voiceover:

Important Safety Information: WARNINGS AND PRECAUTIONS: Interstitial Lung Disease (ILD)/Pneumonitis: Severe, life-threatening, and fatal pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis have occurred with ALUNBRIG. In ALTA 1L, ILD/pneumonitis occurred in 5.1% of patients receiving ALUNBRIG. ILD/pneumonitis occurred within 8 days of initiation of ALUNBRIG in 2.9% of patients, with Grade 3 to 4 reactions occurring in 2.2% of patients. In ALTA, ILD/pneumonitis occurred in 3.7% of patients in the 90 mg group (90 mg once daily) and 9.1% of patients in the 90→180 mg group (180 mg once daily with 7-day lead-in at 90 mg once daily). Adverse reactions consistent with possible ILD/pneumonitis occurred within 9 days of initiation of ALUNBRIG (median onset was 2 days) in 6.4% of patients, with Grade 3 to 4 reactions occurring in 2.7% of patients. Monitor for new or worsening respiratory symptoms (dyspnea, cough, etc.), particularly during the first week of initiating ALUNBRIG. Withhold ALUNBRIG in any patient with new or worsening respiratory symptoms, and promptly evaluate for ILD/pneumonitis or other causes of respiratory symptoms (e.g., pulmonary embolism, tumor progression, and infectious pneumonia). For Grade 1 or 2 ILD/pneumonitis, either resume ALUNBRIG with dose reduction according to Table 1 of the full Prescribing Information 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. 

Hypertension: In ALTA 1L, hypertension was reported in 32% of patients receiving ALUNBRIG; 13% of patients experienced Grade 3 hypertension. In ALTA, hypertension was reported in 11% of patients in the 90 mg group and 21% of patients in the 90→180 mg group. Grade 3 hypertension occurred in 5.9% of patients overall. Control blood pressure prior to treatment with ALUNBRIG. Monitor blood pressure after 2 weeks and at least monthly thereafter during treatment with ALUNBRIG. Withhold ALUNBRIG for Grade 3 hypertension despite optimal antihypertensive therapy. Upon resolution or improvement to Grade 1, resume ALUNBRIG at the same dose. Consider permanent discontinuation of treatment with ALUNBRIG for Grade 4 hypertension or recurrence of Grade 3 hypertension. Use caution when administering ALUNBRIG in combination with antihypertensive agents that cause bradycardia.

Bradycardia: In ALTA 1L, heart rates less than 50 beats per minute (bpm) occurred in 8.1% of patients receiving ALUNBRIG; one patient (0.7 %) experienced Grade 3 bradycardia. In ALTA, heart rates less than 50 beats per minute (bpm) occurred in 5.7% of patients in the 90 mg group and 7.6% of patients in the 90→180 mg group. One patient (0.9%) in the 90 mg group experienced Grade 2 bradycardia. Monitor heart rate and blood pressure during treatment with ALUNBRIG. Monitor patients more frequently if concomitant use of drug known to cause bradycardia cannot be avoided. For symptomatic bradycardia, withhold ALUNBRIG and review concomitant medications for those known to cause bradycardia. If a concomitant medication known to cause bradycardia is identified and discontinued or dose adjusted, resume ALUNBRIG at the same dose following resolution of symptomatic bradycardia; otherwise, reduce the dose of ALUNBRIG following resolution of symptomatic bradycardia. Discontinue ALUNBRIG for life -threatening bradycardia if no contributing concomitant medication is identified.

Visual Disturbance: In ALTA 1L, Grade 1 or 2 adverse reactions leading to visual disturbance, including blurred vision, photophobia, photopsia, and reduced visual acuity, were reported in 7.4% of patients receiving ALUNBRIG. In ALTA, adverse reactions leading to visual disturbance, including blurred vision, diplopia, and reduced visual acuity, were reported in 7.3% of patients treated with ALUNBRIG in the 90 mg group and 10% of patients in the 90→180 mg group. Grade 3 macular edema and cataract occurred in one patient each in the 90→180 mg group. Advise patients to report any visual symptoms. Withhold ALUNBRIG and obtain an ophthalmologic evaluation in patients with new or worsening visual symptoms of Grade 2 or greater severity. Upon recovery of Grade 2 or Grade 3 visual disturbances to Grade 1 severity or baseline, resume ALUNBRIG at a reduced dose. Permanently discontinue treatment with ALUNBRIG for Grade 4 visual disturbances.

Creatine Phosphokinase (CPK) Elevation: In ALTA 1L, creatine phosphokinase (CPK) elevation occurred in 81% of patients who received ALUNBRIG. The incidence of Grade 3 or 4 CPK elevation was 24%. Dose reduction for CPK elevation occurred in 15% of patients. In ALTA, CPK elevation occurred in 27% of patients receiving ALUNBRIG in the 90 mg group and 48% of patients in the 90→180 mg group. The incidence of Grade 3 to 4 CPK elevation was 2.8% in the 90 mg group and 12% in the 90→180 mg group. Dose reduction for CPK elevation occurred in 1.8% of patients in the 90 mg group and 4.5% of patients in the 90→180 mg group. Advise patients to report any unexplained muscle pain, tenderness, or weakness. Monitor CPK levels during ALUNBRIG treatment. Withhold ALUNBRIG for Grade 3 or 4 CPK elevation with Grade 2 or higher muscle pain or weakness. Upon resolution or recovery to Grade 1 CPK elevation or baseline, resume ALUNBRIG at the same dose or at a reduced dose per Table 2 of the full Prescribing Information. 

Pancreatic Enzyme Elevation: In ALTA 1L, amylase elevation occurred in 52% of patients and Grade 3 or 4 amylase elevation occurred in 6.8% of patients who received ALUNBRIG. Lipase elevations occurred in 59% of patients and Grade 3 or 4 lipase elevation occurred in 17% of patients. In ALTA, amylase elevation occurred in 27% of patients in the 90 mg group and 39% of patients in the 90→180 mg group. Lipase elevations occurred in 21% of patients in the 90 mg group and 45% of patients in the 90→180 mg group. Grade 3 or 4 amylase elevation occurred in 3.7% of patients in the 90 mg group and 2.7% of patients in the 90→180 mg group. Grade 3 or 4 lipase elevation occurred in 4.6% of patients in the 90 mg group and 5.5% of patients in the 90→180 mg group. Monitor lipase and amylase during treatment with ALUNBRIG. Withhold ALUNBRIG for Grade 3 or 4 pancreatic enzyme elevation. Upon resolution or recovery to Grade 1 or baseline, resume ALUNBRIG at the same dose or at a reduced dose.

Hepatotoxicity: In ALTA 1L, aspartate aminotransferase (AST) elevations occurred in 72% of patients and Grade 3 or 4 AST elevations occurred in 4.5% of patients who received ALUNBRIG. Alanine aminotransferase (ALT) elevations occurred in 52% of patients and Grade 3 or 4 ALT elevations occurred in 5.2% of patients. One patient (0.7%) had a serious adverse reaction of hepatocellular injury. In ALTA, AST elevations occurred in 38% of patients in the 90 mg group and 65% of patients in the 90→180 mg group. ALT elevations occurred in 34% of patients in the 90 mg group and 40% of patients in the 90→180 mg group. Grade 3 or 4 AST elevations occurred in 0.9% of patients in the 90 mg group and did not occur in any patients in the 90→180 mg group. Grade 3 or 4 ALT elevations did not occur in any patients in the 90 mg group and in 2.7% of patients in the 90→180 mg group. Monitor AST, ALT and total bilirubin during treatment with ALUNBRIG, especially during the first 3 months. Withhold ALUNBRIG for Grade 3 or 4 hepatic enzyme elevation with bilirubin less than or equal to 2 × ULN. Upon resolution or recovery to Grade 1 or less (less than or equal to 3 × ULN) or to baseline, resume ALUNBRIG at a next lower dose per Table 2 of the full Prescribing Information. Permanently discontinue ALUNBRIG for Grade 2 to 4 hepatic enzyme elevation with concurrent total bilirubin elevation greater than 2 times the ULN in the absence of cholestasis or hemolysis.

Hyperglycemia: In ALTA 1L, 56% of patients who received ALUNBRIG experienced new or worsening hyperglycemia. Grade 3 hyperglycemia, based on laboratory assessment of serum fasting glucose levels, occurred in 7.5% of patients. In ALTA, 43% of patients who received ALUNBRIG experienced new or worsening hyperglycemia. Grade 3 hyperglycemia, based on laboratory assessment of serum fasting glucose levels, occurred in 3.7% of patients. Two of 20 (10%) patients with diabetes or glucose intolerance at baseline required initiation of insulin while receiving ALUNBRIG. Assess fasting serum glucose prior to initiation of ALUNBRIG and monitor periodically thereafter. Initiate or optimize anti -hyperglycemic medications as needed. If adequate hyperglycemic control cannot be achieved with optimal medical management, withhold ALUNBRIG until adequate hyperglycemic control is achieved and consider reducing the dose of ALUNBRIG dosage per Table 1 of the full Prescribing Information or permanently discontinuing ALUNBRIG.

Photosensitivity: In ALTA 1L, 3.7% of patients who received ALUNBRIG experienced photosensitivity, with 0.7% of patients experiencing Grade 3 to 4 reactions. In ALTA, 0.9% of patients who received ALUNBRIG in the 90 mg group and 0.9% of patients in the 90→180 mg group experienced photosensitivity. 
Grade 3 to 4 photosensitivity was not reported in patients in the 90 mg group or in the 90→180 mg group. Advise patients to limit sun exposure while taking ALUNBRIG, and for at least 5 days after discontinuation of treatment. Advise patients, when outdoors, to wear a hat and protective clothing, and use a broad - spectrum Ultraviolet A (UVA)/ Ultraviolet B (UVB) sunscreen and lip balm (SPF ≥30) to help protect against sunburn. Based on the severity, withhold ALUNBRIG, then resume at the same dose, or reduce the dose, or permanently discontinue.

Embryo-Fetal Toxicity: Based on its mechanism of action and findings in animals, ALUNBRIG can cause fetal harm when administered to pregnant women. There are no clinical data on the use of ALUNBRIG in pregnant women. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ALUNBRIG and for at least 4 months following the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose of ALUNBRIG. 

ADVERSE REACTIONS 

The most common adverse reactions (≥25%) with ALUNBRIG were diarrhea, fatigue, nausea, rash, cough, myalgia, headache, hypertension, vomiting, and dyspnea. 

DRUG INTERACTIONS 

CYP3A Inhibitors: Avoid coadministration of ALUNBRIG with strong or moderate CYP3A inhibitors. If coadministration of a strong or moderate CYP3A inhibitor is unavoidable, reduce the dose of ALUNBRIG. 

CYP3A Inducers: Avoid coadministration of ALUNBRIG with strong or moderate CYP3A inducers. If coadministration of a moderate CYP3A inducer is unavoidable, increase the dose of ALUNBRIG.

USE IN SPECIFIC POPULATIONS 

Females and Males of Reproductive Potential 

Verify pregnancy status in females of reproductive potential prior to initiating ALUNBRIG. Advise females of reproductive potential to use effective contraception during treatment with ALUNBRIG and for at least 4 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ALUNBRIG and for at least 3 months after the final dose. ALUNBRIG may cause reduced fertility in males. 

Lactation: Advise patients not to breastfeed. 

Hepatic Impairment: Reduce the dose of ALUNBRIG for patients with severe hepatic impairment. 

Renal Impairment: Reduce the dose of ALUNBRIG for patients with severe renal impairment. 

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals U.S.A., Inc. at 1 -844 -217 -6468 or the FDA at 1 - 800 -FDA -1088 or www.fda.gov/medwatch. 

Please see full Prescribing Information.

Dr. Albino:
Thank you for joining me.

Voiceover:

This program is sponsored by Takeda Pharmaceuticals U.S.A., Inc., and has been brought to you by PeerDirect Publishing. Thank you for your participation.

Acronyms:
ALK=anaplastic lymphoma kinase; AR=adverse reaction; BIRC=blinded independent review committee; CNS=central nervous system; CPK=creatine phosphokinase; CR=complete response; CTCAE=Common Terminology Criteria for Adverse Events; DOR=duration of response; ECOG PS=Eastern Cooperative Oncology Group performance status; EORTC QLQ-C30=European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; FDA=US Food and Drug Administration; GHS=global health status; HR=hazard ratio; ICR=intracranial response; ITT=intention to treat; KRAS=Kirsten RAt Sarcoma virus; mNSCLC=metastatic non-small cell lung cancer; NCCN=National Comprehensive Cancer Network^® (NCCN^®); NSCLC=non-small cell lung cancer; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; PR=partial response; QLQ-LC13=Quality of Life Questionnaire Lung Cancer 13; QoL=quality of life; RECIST=Response Evaluation Criteria in Solid Tumors.

Slide/Video References:

1. O’Kane GM, Su J, Tse BC, et al. The impact of brain metastases and associated neurocognitive aspects on health utility scores in EGFR mutated and ALK rearranged NSCLC: a real world evidence analysis. Oncologist. 2019;24(7):e501-e509. 
2. Pérez-Larraya JG, Hildebrand J. Brain metastases. Handb Clin Neurol. 2014;121:1143-1157. 
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. 2018;14(4):691-700. 
4. Eton DT, Ridgeway JL, Egginton JS, et al. Finalizing a measurement framework for the burden of treatment in complex patients with chronic conditions. Patient Relat Outcome Meas. 2015;6:117-126. 
5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer v3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed May 1, 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. 
6. ALUNBRIG. Prescribing information. Takeda Pharmaceuticals America, Inc; 2022. 
7. 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. 
8. Takeda Pharmaceuticals U.S.A., Inc. Data on file. 
9. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK inhibitor–naïve advanced ALK-positive NSCLC: final results of phase 3 ALTA-1L trial. J Thorac Oncol. 2021;16(12):2091-2108. 
10. 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. 
11. Tang W, Lei Y, Su J, et al. TNM stages inversely correlate with the age at diagnosis in ALK-positive lung cancer. Transl Lung Cancer Res. 2019;8(2):144-154.

Voiceover References:

1. O’Kane GM, Su J, Tse BC, et al. The impact of brain metastases and associated neurocognitive aspects on health utility scores in EGFR mutated and ALK rearranged NSCLC: a real world evidence analysis. Oncologist. 2019;24(7):e501-e509. 
2. Chia PL, Mitchell P, Dobrovic A, John T. Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors. Clin Epidemiol. 2014;6:423-432. 
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. 2018;14(4):691-700. 
4. Pérez-Larraya JG, Hildebrand J. Brain metastases. Handb Clin Neurol. 2014;121:1143-1157. 
5. Eton DT, Ridgeway JL, Egginton JS, et al. Finalizing a measurement framework for the burden of treatment in complex patients with chronic conditions. Patient Relat Outcome Meas. 2015;6:117-126. 
6. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer v3.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed May 1, 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. 
7. 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. 
8. ALUNBRIG. Prescribing information. Takeda Pharmaceuticals America, Inc; 2022. 
9. Takeda Pharmaceuticals U.S.A., Inc. Data on file. 
10. Camidge DR, Kim HR, Ahn MJ, et al. Brigatinib versus crizotinib in ALK inhibitor–naïve advanced ALK-positive NSCLC: final results of phase 3 ALTA-1L trial. J Thorac Oncol. 2021;16(12):2091-2108. 
11. 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.