Article
Bringing Precision Medicine to Community Oncology is Going to Require Bigger Thinking
Precision medicine is continuing to redefine how we approach cancer treatment and advance the oncology treatment landscape at an unprecedented rate – especially for lung cancer.
Sponsored Content by Takeda Oncology
Chris Danes
Scientific Director
US Medical Affairs for Lung Cancer
Takeda Oncology
This rapidly evolving approach to treatment is leading to the identification of new biomarkers and disease-causing mutations seemingly every day, driving an avalanche of targeted therapeutic development.1 Since its start in the early 2000s, precision oncology, the application of molecular profiling and genetic tools to treat tumors, has provided more targeted treatment options compared to traditional chemotherapeutic approaches.2-3
Previously, patients with late-stage or metastatic lung cancer were usually presented with two options – chemotherapy or palliative care.4 But now, we are finding that more than 70% of patients with non-small cell lung cancer (NSCLC) have a driver mutation that is potentially treatable with targeted therapy.5
For instance, NSCLC tumors identified as anaplastic lymphoma kinase-positive (ALK+) have been notoriously difficult to treat.6 Thanks to precision medicine and genetic profiling, today, we can identify and treat this particularly aggressive cancer at its source with targeted treatment.7
Patients with this form of NSCLC have unique characteristics compared to the broader NSCLC population. They tend to be younger than most NSCLC patients, at an average age of 52, and the majority of patients with ALK+ NSCLC are light or non-smokers.8-9 Because many of these patients do not fit the standard criteria for a lung cancer screening (individuals above the age of 50 who have a history of smoking) their cancer often goes undetected and moves to the advanced stages.10 In fact, up to 35% of ALK+ NSCLC patients may already have brain metastases at the time of diagnosis.11 These considerations amplify the importance of identifying the ALK gene at diagnosis so a patient with advanced-stage disease can receive a treatment that will specifically target their cancer. In under a decade, five targeted therapies were approved by the U.S. Food and Drug Administration (FDA) for ALK+ metastatic non-small cell lung cancer (mNSCLC) alone.12 These targeted treatment options have made remarkable progress for patients, improving the disease prognosis and extending the median survival rate beyond five years.13
While the benefits of precision medicine are undeniable, this rapid rate of discovery can often outpace the rate at which community oncologists are able to keep up with the latest advancements, impacting their ability to provide the newest, most powerful treatment options to the diverse communities who may need them the most.
At one time, new targeted treatments and immunotherapies would have been rare, but now there seems to be a new one every week. As exciting as this is, it also means that it is getting increasingly difficult for providers to keep up. It’s no longer good enough to identify that a patient has a certain mutation – we have to understand each individual mutation indicated by a patient’s biomarkers on a deep, molecular level. For example, for oncogenic drivers like ALK and epidermal growth factor receptor (EGFR), identifying the mutation is not always enough to confirm the diagnosis. We need to understand the underlying mechanisms of the mutation to develop and provide precise, targeted therapies for those unique causes of cancer. The newest, most targeted therapies may require comprehensive biomarker testing or up-to-the-minute knowledge on recent approvals, presenting community providers with a mountain of information to process and apply for dozens of patients with unique cancers. For community oncologists, who make up nearly 80% of all oncology caregivers and treat all types of unique cancers, this is an unfair challenge.14-15
Major cancer centers are equipped to handle these rapid changes, and many have molecular tumor boards who will assess biomarker reports for providers and look at an amino acid sequence, know what it is and then match it to a therapy. Community oncologists don’t have these systems and safety nets. In many ways, for this crucial group of health care providers, molecular testing and precision medicine are the wild west; there are so many new testing companies, without a standardized way to present the report. For someone who is not a molecular biologist, it can be overwhelming.
To add to this, community providers are still straining in the wake of COVID-19. In 2021 alone at least 230,000 HCPs left their practice, many of them due to burnout, poor management and a lack of resources.16 The oncologists who are still practicing in communities have lost staff, and crucially, time. They are seeing dozens of patients a day with all types of cancers – there simply isn’t time to stay on the cutting edge of everything, let alone the numerous biomarker testing recommendations or available data behind approved targeted therapies.
To best equip community oncologists who are caring for the vast majority of patients, companies have a responsibility to support and educate them, while helping to expand access to these newer, more powerful treatments.
Medical education and support for community oncologists must evolve with the increasingly complex therapeutic landscape. At Takeda, we have been seriously asking where this next generation of support is going to come from; we are asking what tools community providers need to make sure they are treating their patients optimally and working to build systems to help them do just that. It is our responsibility to make sure that every community oncologist has what they need to treat their patients properly and leverage the potential of precision medicine for more patients.
We want community oncologists and their patients to have access to precision therapies, like ALUNBRIG® (brigatinib), with the potential to transform the trajectory of patient outcomes. ALUNBRIG is a next-generation tyrosine kinase inhibitor (TKI) designed to target ALK+ mNSCLC.17 This treatment could be life-changing for certain patients – and it is our job to ensure it’s explored as an option for people living with ALK+ mNSCLC.
In the United States (U.S.), ALUNBRIG is approved for the treatment of adult patients with ALK+ mNSCLC as detected by a U.S. FDA-approved test.18 ALUNBRIG has demonstrated safety and efficacy, and robust, durable responses even in complex stages of ALK+ NSCLC that has metastasized to the brain.17
Offerings like Takeda’s ALUNBRIG are bringing the targeted precision medicine technologies that patients need directly to communities and patients with the help of cutting-edge science as well as through resources for HCPs. The powerful treatment improvements enabled by selective new therapies have the potential to improve not only the cancer therapy landscape but the patient experience.
Click here to learn about the efficacy and safety of ALUNBRIG in this patient population. Learn more about ALK+ mNSCLC and ALUNBRIG by visiting ALUNBRIG.com.
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.
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 the full U.S. Prescribing Information for ALUNBRIG at www.ALUNBRIG.com
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12 Rijavec E, Biello F, Indini A, Grossi F, Genova C. Current Insights on the Treatment of Anaplastic Lymphoma Kinase-Positive Metastatic Non-Small Cell Lung Cancer: Focus on Brigatinib. Clin Pharmacol. 2022;14:1-9. Published 2022 Jan 20. doi:10.2147/CPAA.S284850
13 Christopoulos P, Budczies J, Kirchner M, et al. Defining molecular risk in ALK+ NSCLC. Oncotarget. 2019;10(33):3093-3103. Published 2019 May 3. doi:10.18632/oncotarget.26886
14 What is Community Oncology? Community Oncology Alliance; 2017. Available at: https://communityoncology.org/wp-content/uploads/2017/08/What-is-Comm-Onc.pdf
15 Wallis, C. a New Wave of Cancer Treatments Challenges Community Oncologists to Keep Up. Scientific American. 2022. https://www.scientificamerican.com/article/a-wave-of-new-cancer-treatments-challenges-community-oncologists-to-keep-up/ Accessed March 1, 2023.
16 Mensik, H. Over 200,000 healthcare workers quit jobs last year. Healthcare Dive. 2022. https://www.healthcaredive.com/news/covid-pandemic-healthcare-burnout-providers-quit-jobs/634946/ Accessed March 1, 2023.
17 ALUNBRIG (brigatinib) Prescribing Information. Takeda Pharmaceutical Company Limited. 2022.
18 Food and Drug Administration. FDA approved brigatinib for ALK-positive metastatic NSCLC. 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-brigatinib-alk-positive-metastatic-nsclc Accessed March 2023.
TAKEDA® and the TAKEDA logo® are registered trademarks of Takeda Pharmaceutical Company Limited. ALUNBRIG® and the ALUNBRIG Logo® are registered trademarks of ARIAD Pharmaceuticals, Inc. © 2023 Takeda Pharmaceuticals U.S.A., Inc. All rights reserved USO-BRG-0667 4/23
