Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
ABEMLETR
Palliative
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.
- For adjuvant treatment of HR+, HER2-, node-positive early breast cancer, in patients who are at high risk of disease recurrence (refer to EAP for abemaciclib funding details)
- For treatment of HR+/HER2- advanced breast cancer in patients who were previously treated with endocrine therapy (abemaciclib not funded by EAP)
abemaciclib
Exceptional Access Program
(abemaciclib - For the adjuvant treatment, in combination with endocrine therapy, of adult patients with HR-positive, HER2-negative, node-positive early breast cancer at high risk of disease recurrence based on clinicopathological features and a Ki-67 score of at least 20%. )
(EAP Website)
letrozole
ODB - General Benefit
(letrozole)
(ODB Formulary
)
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abemaciclib * | 150 mg | PO | BID |
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| letrozole | 2.5 mg | PO | Daily |
Note: Pre- or perimenopausal women, and men should also be treated with gonadotropin releasing hormone (GnRH) agonists according to local clinical practice.
CONTINUOUS TREATMENT
Early breast cancer: Up to a total of 2 years of treatment, unless disease progression/ unacceptable toxicity occurs. Letrozole monotherapy may continue.
Advanced or metastatic breast cancer: Until disease progression or unacceptable toxicity
Minimal – No routine prophylaxis; PRN recommended
Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.
Assess patient’s risk factors for osteoporosis and consider calcium and vitamin D supplements and bisphosphonates where appropriate. Refer patients to the Bone Health During Cancer Treatment pamphlet for more information.
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
Abemaciclib
| Dose Level | Abemaciclib Dose (mg BID) |
| 0 | 150 |
| -1 | 100 |
| -2 | 50 |
| -3 | Discontinue |
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Toxicity |
Grade |
Abemaciclib Action |
Letrozole Action |
| Hematologic* | Grade 3 | Hold until ≤ grade 2; resume at same dose. | No dosage adjustment required. |
| Grade 4 or recurrent grade 3 | Hold until ≤ grade 2; resume at 1 dose level ↓. | ||
| Diarrhea** | Grade 2 |
If no resolution to ≤ grade 1 within 24 hours, hold until resolution; resume at same dose. |
No adjustment required |
| Grade 2 that persists/recurs after resumption at the same dose (despite maximal supportive measures) | Hold until ≤ grade 1; resume at 1 dose level ↓. | ||
| ≥ Grade 3 or requires hospitalization | |||
| Interstitial lung disease (ILD)/ Pneumonitis | Persistent or recurrent grade 2 toxicity that does not resolve to baseline or grade 1 within 7 days (despite maximal supportive measures) | Hold until recovery to baseline or ≤ grade 1; resume at 1 dose level ↓. | Not applicable |
| Grade 3 or 4 | Discontinue | ||
| Hepatotoxicity | Persistent or recurrent grade 2, or grade 3 (ALT, AST >5 to 20 times ULN), WITHOUT increase in total bilirubin >2 times ULN | Hold until recovery to baseline or grade 1; resume at 1 dose level ↓. | Refer to “hepatic impairment” table below |
| AST and/or ALT >3 times ULN with total bilirubin >2 times ULN (in the absence of cholestasis) | Discontinue | ||
| Grade 4 (ALT, AST >20 times ULN) | Discontinue | ||
| Venous thromboembolism | Grade 1 or 2 |
Early breast cancer: Hold; restart when patient is stable and if clinically appropriate Metastatic breast cancer: No dose modification required |
Not applicable |
| Grade 3 or 4 | For early or metastatic breast cancer: Hold; restart when patient is stable and if clinically appropriate | ||
| All other non-hematologic toxicities | Persistent or recurrent grade 2 toxicity that does not resolve to baseline or grade 1 within 7 days (despite maximal supportive measures) | Hold until recovery to baseline or ≤ grade 1; resume at 1 dose level ↓. | No adjustment required |
| Grade 3 or 4 |
*If blood cell growth factors are required, hold abemaciclib for at least 48 hours after the last growth factor dose and until toxicity resolves to ≤ grade 2; resume at the next lower dose (unless already reduced due to the toxicity that required the growth factor). Growth factor use is as per current local guidelines.
**At the first sign of loose stools, begin management with antidiarrheal agents (i.e. loperamide) and increase oral fluid intake.
Hepatic Impairment
| Hepatic Impairment | Abemaciclib Dose | Letrozole Dose |
| Mild or moderate impairment (Child-Pugh class A or B) | No dosage adjustment necessary. | No dose adjustment needed, although exposure may ↑ by 37% |
| Severe impairment (Child-Pugh class C) | Reduce abemaciclib frequency to once daily. | No data. Monitor patients closely and consider dose modification. |
Renal Impairment
| Renal Impairment | Abemaciclib Dose | Letrozole Dose |
| Mild or Moderate (CrCl ≥ 30 mL/min) | No dosage adjustment required. | No dose adjustment required.* |
| Severe (CrCl 10-29 mL/min) | Has not been studied | |
| Severe (CrCl <10 mL/min); ESRD | No data. Consider potential benefit-risk carefully. |
Dosage in the Elderly
No dosage adjustment is required. Patients ≥65 years of age on abemaciclib reported more hematologic adverse events, hypokalemia (including grade 3), hypocalcemia, grade ≥3 infections, decreased appetite, and increased blood creatinine compared to younger patients with abemaciclib in a subgroup analysis from clinical studies. Older patients on letrozole have an increased risk of osteoporosis and fracture.
Dosage based on Ethnicity
No dose adjustment based on race is required. Higher incidences of increased ALT and AST and neutropenia have been reported in East Asian patients on abemaciclib compared to Caucasian patients in clinical trials.
Refer to abemaciclib, letrozole 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 abemaciclib, letrozole drug monograph(s) for additional details
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Avoid co-administration of abemaciclib with strong CYP3A inhibitors. Use caution when abemaciclib is co-administered with moderate or weak CYP3A inhibitors.
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If co-administration with a strong or moderate CYP3A inhibitor is unavoidable, reduce abemaciclib dose to 50 mg twice daily.
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When combined with ketoconazole, abemaciclib dose should be reduced to 50 mg once daily.
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When combined with clarithromycin, diltiazem or verapamil, abemaciclib dose should be reduced to 100 mg twice daily.
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If co-administration with a weak CYP3A inhibitor is unavoidable, reduce abemaciclib dose to 100 mg twice daily.
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If the CYP3A inhibitor is discontinued, increase the abemaciclib dose (after 3-5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor.
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Avoid co-administration of abemaciclib with strong CYP3A inducers. Consider alternative agents with less CYP3A induction. Use with caution when co-administered with moderate or weak CYP3A inducers.
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Avoid concomitant use with tamoxifen, other anti-estrogens, estrogen-containing or estrogenic therapies due to the risk of decreased letrozole efficacy.
Refer to abemaciclib, letrozole drug monograph(s) for additional details
Administration
Abemaciclib
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Abemaciclib tablets should be swallowed whole (do not to chew, crush, or split tablets before swallowing). Tablets should not be ingested if they are not intact.
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Abemaciclib doses may be taken with or without food and should be administered at approximately the same times every day.
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Avoid fruit or juice from grapefruit, Seville oranges or starfruit.
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Abemaciclib tablets contain lactose. Use with caution in patients with lactose intolerance.
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If a dose is missed or vomited, the next dose should be taken at the scheduled time. The patient should not take 2 doses at the same time to make up for the missed dose.
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Store at room temperature (15°C to 30°C).
Letrozole
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Tablets should be taken with a glass of water, with or without food, at around the same time every day.
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Do not crush or chew the tablets.
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Missed doses should be taken as soon as possible, but should be skipped if within a few hours (e.g. within 2 or 3 hours) of the next planned dose. Do not double the dose due to over-proportionality of exposure at doses above 2.5 mg daily.
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Store tablets at room temperature (15-30°C)
Contraindications
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Patients who are hypersensitive to abemaciclib, letrozole or to any of their components, or to other aromatase inhibitors.
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Letrozole is contraindicated in pregnancy and/or breastfeeding or in patients who are <18 years of age.
Other Warnings/Precautions
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There are no data regarding abemaciclib safety or efficacy in patients with prior exposure to other CDK 4/6 inhibitors.
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Letrozole is not indicated in hormone-receptor negative disease.
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Use of formulations containing lactose should be carefully considered in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
Pregnancy/Lactation
- This treatment is contraindicated in pregnancy. Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.
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Breastfeeding is contraindicated during this treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
- Fertility Effects:
- Abemaciclib: Probable; may impair fertility in males
- Letrozole: Probable
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.
Recommended Clinical Monitoring
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CBC; Baseline, every two weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated
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Liver function tests; Baseline, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated
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Renal function tests*; Baseline and as clinically indicated
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Bone mineral density; Baseline and as clinically indicated
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Serum cholesterol and lipids evaluation; Baseline and as clinically indicated
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Clinical toxicity assessment for signs and symptoms of thromboembolism, infections, estrogen withdrawal symptoms, musculoskeletal, cardiovascular, respiratory, dermatologic, ophthalmic, GI, GU effects and fatigue; At each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
*Abemaciclib may increase serum creatinine, without affecting glomerular function, by inhibiting renal tubular secretion transporters. Consider alternative markers that are not based on creatinine (e.g. BUN) for determining renal function.
Suggested Clinical Monitoring
- Electrolytes, including calcium; Baseline and as clinically indicated
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Abemaciclib drug monograph, Cancer Care Ontario.
CADTH reimbursement review: Abemaciclib (Adjuvant treatment of hormone receptor–positive, human epidermal growth factor receptor 2–negative early breast cancer), December 2022.
Goetz MP, Toi M, Campone M, et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35:3638-46.
Johnston SRD, Harbeck N, Hegg R. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early Breast Cancer (monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987-98.
Letrozole drug monograph, Cancer Care Ontario.
October 2023 Modified Rationale/uses and Pregnancy/lactation sections; added abemaciclib funding information
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.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.