Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
BRIG
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
Treatment of:
- anaplastic lymphoma kinase (ALK)-positive locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC) previously untreated with an ALK inhibitor, in patients with good performance status
- ALK-positive metastatic NSCLC, in patients who have progressed on or who were intolerant to an ALK inhibitor (crizotinib)*
*Not funded by EAP
brigatinib
Exceptional Access Program
(brigatinib - For the treatment of anaplastic lymphoma kinase-positive locally advanced or metastatic non-small cell lung cancer according to clinical criteria)
(EAP Website)
ALK-positive status must be based on a validated assay, prior to starting treatment with brigatinib.
Blood pressure should be controlled prior to initiating brigatinib therapy.
| brigatinib | 90 mg | PO | Daily on Days 1-7 |
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Then, |
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| brigatinib | 180 mg | PO | Daily |
Minimal – No routine prophylaxis; PRN recommended
Other Supportive Care:
Also refer to CCO Antiemetic Recommendations.
Doses should be modified according to the protocol by which the patient is being treated.
If therapy is interrupted for ≥14 days due to reasons other than toxicity, resume treatment at 90mg once daily for 7 days before escalating dose to the previously tolerated dose.
If dose is reduced for toxicity, do not subsequently escalate the dose.
See Interactions section for dosing recommendations when administered with CYP3A4 inhibitors/inducers.
Dosage with toxicity
Dose Levels
| Dose Level |
Initial Brigatinib Dose (first 7 days) (mg/day) |
Maintenance Brigatinib Dose (mg/day) |
| 0 | 90 | 180 |
| -1 | 60 | 120 |
| -2 | Discontinue | 90 |
| -3 | N/A | 60 |
| -4 | N/A | Discontinue |
| Toxicity | Severity | Action | |
| Interstitial Lung Disease (ILD) /Pneumonitis | Grade 1 |
Hold until recovery to baseline; resume at same dose level. If recurs, discontinue. |
|
| Grade 2 |
Hold until recovery to baseline; resume at 1 dose level ↓. If recurs, discontinue. |
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| ≥ Grade 3 | Discontinue. | ||
| Hypertension |
Grade 3 |
Hold until recovery to ≤ grade 1; resume at same dose level. |
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| Grade 4 |
Hold until recovery to ≤grade 1; resume at 1 dose level ↓ or discontinue. If recurs, discontinue. |
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| Bradycardia (HR <60 bpm) | Symptomatic |
Hold until recovery to asymptomatic or resting heart rate ≥60 bpm; If contributing medication identified and discontinued (or dose-adjusted), resume at same dose. If no contributing medication identified (or cannot be discontinued or dose-adjusted), resume at 1 dose level ↓. |
|
| Life-threatening (urgent intervention indicated) |
Hold until recovery to asymptomatic or resting heart rate ≥60 bpm; If contributing medication identified and discontinued (or dose-adjusted), resume at 1 dose level ↓ If no contributing medication identified, discontinue. If recurs, discontinue. |
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| Visual Disturbance | Grade 2-3 | Hold until recovery to ≤grade 1 or baseline; resume at 1 dose level ↓. | |
| Grade 4 | Discontinue. | ||
| Creatine Phosphokinase (CPK) Elevation |
≥Grade 3 with ≥grade 2 muscle pain or weakness |
Hold until recovery to ≤grade 1 or baseline; resume at same dose level. If recurs, hold until recovery to ≤grade 1 or baseline; resume at 1 dose level ↓. |
|
| Lipase/Amylase Elevation | Grade 3 | Hold until recovery to ≤ grade 1 or baseline; resume at same dose. | |
| Recurrent Grade 3 or grade 4 | Hold until recovery to ≤ grade 1 or baseline; resume at 1 dose level ↓. | ||
| Hyperglycemia | Blood glucose >13.9 mmol/L | Hold until adequate hyperglycemic control; resume at 1 dose level ↓ or discontinue. | |
| Elevation of hepatic enzymes |
≥Grade 3 AST/ALT with bilirubin ≤2 × ULN | Hold until recovery to ≤3 x ULN or baseline; resume at 1 dose level ↓. | |
| ≥Grade 2 AST/ALT with bilirubin >2 × ULN in the absence of cholestasis or hemolysis | Discontinue. | ||
| Other Toxicities | Grade 3 |
Hold until recovery to baseline; resume at same dose level. |
|
| Grade 4 |
Hold until recovery to baseline; resume at 1 dose level ↓. If recurs, hold until recovery to baseline; resume at 1 dose level ↓ or discontinue. |
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Hepatic Impairment
| Hepatic Impairment | Brigatinib Dose (mg/day) |
| Mild or moderate (Child-Pugh class A or B) | No dose adjustment required |
| Severe (Child-Pugh class C) | Reduce dose by 1 dose level |
Renal Impairment
| Renal Impairment | Brigatinib Dose (mg/day) |
|
Mild or moderate (CrCl ≥30 mL/min) |
No dose adjustment required |
| Severe (CrCl <30 mL/min) |
For 180mg dose: Reduce by 2 dose levels For 90mg dose: Reduce by 1 dose level |
Dosage in the Elderly
No dosage adjustment is required. Use brigatinib with caution in elderly patients, especially patients > 85 years of age as there is no available data on patients in this age group. Increased age (≥ 65 years of age) was associated with an increased risk of early pulmonary adverse reactions.
Refer to brigatinib drug monograph(s) for additional details of adverse effects.
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Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
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Refer to brigatinib drug monograph(s) for additional details.
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Avoid co-administration with strong or moderate CYP3A inhibitors as concurrent use may increase brigatinib concentration and/or toxicity.
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If concomitant use of strong inhibitors cannot be avoided, reduce brigatinib dose from 180mg to 90mg, or from 90mg to 60mg.
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If concomitant use of moderate inhibitors cannot be avoided, reduce brigatinib dose from 180mg to 120mg, or 120mg to 90mg, or 90mg to 60mg.
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After discontinuation of strong or moderate CYP3A inhibitor, resume brigatinib at dose that was tolerated prior to the initiation of the CYP3A inhibitor.
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Do not administration with strong CYP3A inducers as concurrent use may decrease brigatinib concentration and/or efficacy.
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Avoid co-administration with moderate CYP3A inducers as concurrent use may decrease brigatinib concentration and/or efficacy.
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If concomitant use cannot be avoided, increase brigatinib dose as follows: after 7 days at current tolerated dose, increase brigatinib dose in 30mg increments, up to a maximum of 2x the brigatinib dose that was tolerated prior to start of inducer.
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After discontinuation of the moderate CYP3A inducer, resume brigatinib at the dose that was tolerated prior to the initiation of the inducer.
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Monitor closely when co-administered with substrates of CYP3A, PXR, P-gp, BCRP, OCT1, MATE1, and MATE2K with narrow therapeutic indices. Concurrent use may affect substrate efficacy or toxicity.
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Avoid if possible co-administration with agents that decrease heart rate. If concomitant use cannot be avoided, monitor heart rate more frequently.
- Use non-hormonal methods of contraception, since the efficacy of hormonal contraceptives may be decreased due to ↑ metabolism.
Refer to brigatinib drug monograph(s) for additional details.
Administration
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Administer with or without food.
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Tablets should be swallowed whole; do not crush or chew.
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Avoid grapefruit, starfruit, Seville oranges, their juices or products during treatment.
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If a dose is missed or vomiting occurs after taking a dose, an additional dose should not be given; administer the next dose at the regularly scheduled time.
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Store at 15°C to 30°C.
Contraindications
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Patients who have a hypersensitivity to this drug or any components of the formulation.
Other Warnings/Precautions
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Caution in patients with bradycardia (<60 beats per minute), a history of syncope or arrhythmia, sick sinus syndrome, sinoatrial block, atrioventricular (AV) block, ischemic heart disease, congestive heart failure or on medications leading to bradycardia.
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Patients with a history of ILD or drug-induced pneumonitis were excluded from clinical trial.
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Brigatinib contains lactose; carefully consider use in patients with lactose intolerance, hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption
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Patients should avoid prolonged sun exposure while taking brigatinib and for at least 5 days after treatment discontinuation. A broad-spectrum UVA/UVB sun screen and lip balm (SPF ≥30) should be used.
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Caution with driving or using machinery as visual disturbances, dizziness, and fatigue may occur with treatment.
Pregnancy and Lactation
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Brigatinib is not recommended for use in pregnancy. Adequate contraception (non-hormonal) should be used during treatment and for at least 4 months in females (and for at least 3 months in males) following the final dose. Hormonal contraceptives may not be effective during brigatinib treatment (See Interactions section).
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Breastfeeding is not recommended during treatment and for 1 week after the last dose.
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Fertility effects: Brigatinib may impair male fertility.
Recommended Clinical Monitoring
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Heart rate and blood pressure; Baseline, after 2 weeks and at least monthly during treatment; more frequently in patients receiving medications known to cause bradycardia.
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Liver Function Tests; Baseline, every 2 weeks for the first 3 months of treatment then as clinically indicated.
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Lipase, amylase, CPK, fasting serum glucose; Baseline, regularly and as clinically indicated.
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Clinical toxicity assessment for fatigue, visual disturbances, pulmonary, dermatological, GI and musculoskeletal effects; At one week (pulmonary) and at each visit.
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Brigatinib drug monograph, Ontario Health (Cancer Care Ontario).
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 Dec;16(12):2091-108.
Camidge DR, Kim HR, Ahn MJ. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med 2018 Nov 22;379(21):2027-39.
Kim D, Tiseo M, Ahn M, et al. Brigatinib in patients With crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial. J Clin Oncol 2017; 35:2490-2498.
June 2022 Updated Premedication and Supportive Measures, Dose Modification, Interactions, Drug Administration/Special Precautions and Clinical Monitoring sections.
Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
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