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.
ABEMFLVS
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 treatment of hormone-receptor-positive, HER2-negative advanced breast cancer in patients whose disease had progressed while receiving endocrine therapy.
fulvestrant
ODB - General Benefit
(fulvestrant)
(ODB Formulary
)
Cycle 1:
| abemaciclib | 150 mg | PO | BID |
| (This drug is not currently publicly funded for this regimen and intent) | |||
| fulvestrant | 500 mg | IM | Days 1 and 15 |
|
Cycle 2+: |
|||
| abemaciclib | 150 mg | PO | BID |
| (This drug is not currently publicly funded for this regimen and intent) | |||
| fulvestrant | 500 mg | IM | Day 1 |
Note: Pre- or perimenopausal women, and men should also be treated with gonadotropin releasing hormone (GnRH) agonists according to local clinical practice.
Abemaciclib: Continuous treatment
Fulvestrant: REPEAT EVERY 28 DAYS
Until disease progression or unacceptable toxicity
Minimal – No routine prophylaxis; PRN recommended
- 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 Levels
| Dose Level | Abemaciclib Dose (mg BID) |
| 0 | 150 |
| -1 | 100 |
| -2 | 50 |
| -3 | Discontinue |
Dose Modifications:
|
Toxicity |
Grade |
Abemaciclib Action |
Fulvestrant Action |
| Hematologic* | Grade 3 | Hold until ≤ grade 2; resume at same dose. | Not applicable |
| 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 | Grade 1 (>ULN-3.0 x ULN) Grade 2 (>3.0-5.0 x ULN) WITHOUT increase in total bilirubin above 2 x ULN |
No dose modification is required. | Hold until recovery then restart |
| 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 ↓. | Discontinue | |
| AST and/or ALT >3 times ULN with total bilirubin >2 times ULN (in the absence of cholestasis) | Discontinue | Discontinue | |
| Grade 4 (ALT, AST >20 times ULN) | Discontinue | Discontinue | |
| Venous thromboembolism | Grade 3 or 4 | Hold; restart when patient is stable and if clinically appropriate | Not applicable |
| Hypersensitivity | ≥ Grade 3 | Hold until recovery to baseline or ≤ grade 1; resume at 1 dose level ↓, OR consider discontinuing. | Consider discontinuing |
| 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 | Fulvestrant Dose |
| Mild or moderate impairment (Child-Pugh class A or B) | No dosage adjustment required. | Use with caution. No dose adjustment required. |
| Severe impairment (Child-Pugh class C) | Reduce the abemaciclib frequency to once daily. | Not studied. Use not recommended. |
Renal Impairment
| Renal Impairment | Abemaciclib Dose | Fulvestrant Dose |
| Mild or Moderate (CrCl ≥ 30 mL/min) | No dosage adjustment required. | No dose adjustment required. |
| Severe (CrCl < 30 mL/min); ESRD | Has not been studied | No data; use with caution. |
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 with abemaciclib compared to younger patients in a subgroup analysis from clinical studies.
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, fulvestrant drug monograph(s) for additional details of adverse effects
|
Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
|
Refer to abemaciclib, fulvestrant drug monograph(s) for additional details
-
Avoid co-administration of abemaciclib with strong CYP3A inhibitors. Use caution when abemaciclib is co-administered with moderate or weak CYP3A inhibitors.
-
If co-administration with a strong or moderate CYP3A inhibitor is unavoidable, reduce abemaciclib dose to 50 mg twice daily.
-
When combined with ketoconazole, abemaciclib dose should be reduced to 50 mg once daily.
-
When combined with clarithromycin, diltiazem or verapamil, abemaciclib dose should be reduced to 100 mg twice daily.
-
-
If co-administration with a weak CYP3A inhibitor is unavoidable, reduce abemaciclib dose to 100 mg twice daily.
-
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.
-
-
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.
-
Fulvestrant may interfere with estradiol immunoassay measurements (falsely elevated estradiol levels) due to its structural similarity with estradiol.
Refer to abemaciclib, fulvestrant drug monograph(s) for additional details
Administration
Abemaciclib
-
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.
-
Abemaciclib doses may be taken with or without food and should be administered at approximately the same times every day.
-
Avoid fruit or juice from grapefruit, Seville oranges or starfruit.
-
Abemaciclib tablets contain lactose. Use with caution in patients with lactose intolerance.
-
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.
-
Store at room temperature (15°C to 30°C).
Fulvestrant
-
Each dose consists of 2 pre-filled syringes (250 mg/5mL). Administer each pre-filled syringe as SLOW intramuscular injection (1-2 minutes per injection) into EACH buttock.
-
Caution should be taken due to proximity of the sciatic nerve and large blood vessels.
-
Administer according to local guidelines at the Cancer Centre or physician's office
-
Store refrigerated at 2 to 8°C in original package
Contraindications
-
Patients who are hypersensitive to abemaciclib, fulvestrant, or to any of their components
-
Fulvestrant is also contraindicated in pregnant and breastfeeding women
Other Warnings/Precautions
-
There are no data regarding abemaciclib safety or efficacy in patients with prior exposure to other CDK 4/6 inhibitors.
-
Use fulvestrant with caution in patients with bleeding disorders or on anticoagulants
-
There is a potential osteoporosis risk due to fulvestrant's mechanism of action.
Pregnancy/Lactation
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This treatment is contraindicated in pregnancy. Adequate contraception should be used by both partners during treatment, and for at least 2 years after the last fulvestrant dose.
-
Breastfeeding is contraindicated with this treatment and not recommended for at least 3 weeks after the last dose of abemaciclib.
-
Fertility Effects:
-
Abemaciclib: Probable; may impair fertility in males
-
Fulvestrant: Probable
-
Recommended Clinical Monitoring
-
CBC; Baseline, every two weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated.
-
Renal function tests*; Baseline and as clinically indicated
-
Liver function tests; Baseline, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated.
- Clinical toxicity assessment for signs and symptoms of thromboembolism, injection site reactions, hypersensitivity, infections, estrogen deprivation symptoms, musculoskeletal, gastrointestinal, respiratory, dermatological effects and fatigue; At each visit
-
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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Outpatient prescription; drug administration at hospital or physician's office
Abemaciclib drug monograph, Ontario Health (Cancer Care Ontario).
Fulvestrant drug monograph, Ontario Health (Cancer Care Ontario).
Sledge GW, Toi M, Neven P, et al. MONARCH 2: Abemaciclib in combination with fulvestrant in women with HR+/HER2- advanced breast cancer who had progressed while receiving endocrine therapy. J Clin Oncol. 2017;35:2875-84.
April 2023 Modified monitoring section
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.