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ALEC

Cancer Type: Lung, Non-Small Cell  Intent: Palliative
Regimen Category: Evidence-Informed
Funding:
Exceptional Access Program
    Treatment of non-small cell lung cancer according to clinical criteria
A - Regimen Name

ALEC Regimen
Alectinib


Disease Site
Lung - Non-Small Cell

Intent
Palliative

Regimen Category
Evidence-Informed :

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.


Rationale and Uses
  • First-line treatment of patients with anaplastic lymphoma kinase (ALK)-positive, locally advanced (not amenable to curative therapy) or metastatic non-small cell lung cancer (NSCLC).
  • Monotherapy for the treatment of patients with (ALK)-positive, locally advanced (not amenable to curative therapy) or metastatic NSCLC who have progressed on or are intolerant to crizotinib.

Supplementary Public Funding

alectinib
Exceptional Access Program (Treatment of non-small cell lung cancer according to clinical criteria)

 
B - Drug Regimen

Patients must have documented ALK-positive status, based on a validated ALK assay, prior to starting treatment with alectinib.

 

 

alectinib
600 mg PO BID

*available as 150 mg capsules

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C - Cycle Frequency

CONTINUOUS TREATMENT

Until disease progression or unacceptable toxicity.

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Low – No routine prophylaxis; PRN recommended

Other Supportive Care:

 

Patients must avoid sun exposure while on treatment and for 7 days after the last dose, and must use UVA/B sunscreen and lip balm (at least SPF 50).

Also refer to CCO Antiemetic Recommendations.

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated.

 Dose reduction levels:

Dose level Dose (mg) BID
Starting Dose 600
- 1 450
- 2 300*

* if unable to tolerate 300 mg bid, permanently discontinue

 

Dosage with toxicity

Toxicity

Action

GI perforation

Discontinue.

ILD/pneumonitis of any Grade

Hold; if confirmed, discontinue.

Grade 3 Renal Impairment

Hold until serum creatinine recovers to baseline or ≤ Grade 1, then resume at 1 dose level ↓.

Grade 4 Renal Impairment

Discontinue.

≥ Grade 3 ALT or AST elevation (> 5 x ULN)

and

Total bilirubin ≤ 2 x ULN

Hold until recovery to baseline or ≤ Grade 1;

Resume at 1 dose level ↓.

≥ Grade 2 ALT or AST elevation (> 3 x ULN)

and

Total bilirubin ≥ 2 x ULN

(in absence of cholestasis or hemolysis)

 

Discontinue.

Grade 2 to 3 Bradycardia (HR < 60 bpm) (symptomatic)

Hold until recovery to ≤ Grade 1 (asymptomatic) bradycardia or HR of ≥ 60 bpm.

Evaluate concomitant medications; if contributing, discontinue or reduce dose of concomitant drug. Resume at previous dose.

If no concomitant medication contributing, or contributing medication not stopped/reduced: resume at 1 dose level ↓

Grade 4 Bradycardia (HR < 60 bpm)

(life-threatening consequences, urgent intervention required)

Discontinue if no contributing concomitant medication.

If contributing concomitant medication is discontinued or reduced: Hold until recovery to ≤ Grade 1 (asymptomatic) bradycardia or HR of ≥ 60 bpm, with frequent monitoring. Resume at 1 dose level ↓.

If recurs: discontinue.

CPK elevation > 5 x ULN

Hold until recovery to baseline or ≤ 2.5 x ULN; resume at same dose.

CPK elevation > 10 x ULN

Or

2nd Occurrence of CPK elevation > 5 x ULN

 

Hold until recovery to baseline or ≤ 2.5 x ULN; resume at 1 dose level ↓.



Hepatic Impairment

Pre-existing Hepatic impairment Alectinib Dose

Mild or Moderate

No dose adjustment required.

Severe

450 mg twice daily.

Renal Impairment

Renal impairment Alectinib dose

Mild or Moderate
(CrCl ≥ 30 mL/min)

No dose adjustment required.
Severe
(CrCl < 30 mL/min)
Has not been studied.

Dosage in the Elderly

No dose adjustment required. Fatal adverse events were more common in patients 65 years or older compared to younger patients.


 
F - Adverse Effects

Refer to alectinib 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

  • Anemia (rarely severe)
  • ↑ LFTs (may be severe)
  • ↑ Creatinine (may be severe)
  • ↑ CPK
  • Constipation
  • Fatigue
  • Musculoskeletal pain
  • Edema
  • Rash
  • Nausea, vomiting
  • Diarrhea
  • Bradycardia
  • Photosensitivity
  • Visual disorders
  • Venous thromboembolism
  • Atrioventricular block
  • GI perforation
  • Pneumonitis/eosinophilic pneumonia
  • QT interval prolonged

 

 

 

 
G - Interactions

Refer to alectinib drug monograph(s) for additional details


  • Caution with strong CYP3A4 inducers, strong CYP3A4 inhibitors, and CYP2C8 substrates. If concomitant use cannot be avoided, monitor closely.

  • Caution with BCRP and P-glycoprotein substrates with a narrow therapeutic index (in vitro increases in substrate concentration).

  • Avoid concomitant use of drugs that lower the heart rate, if possible, due to additive effects. If clinically important bradycardia occurs, discontinue or adjust dosage of the concomitant drug, if possible.

  • No dose adjustment is necessary with CYP3A4 substrates.

 

 
H - Drug Administration and Special Precautions

Refer to alectinib drug monograph(s) for additional details


Administration 

  • Oral self-administration; drug available by outpatient prescription.

  • Alectinib should be taken twice daily with food (fasted state decreases exposure three fold).

  • If a dose is missed the next dose should be taken at the next scheduled time.

  • If vomiting occurs, a repeat dose should not be taken; the next dose should be taken at the next scheduled time.

  • Caution with grapefruit, grapefruit juice, products with grapefruit extract, star fruit, Seville oranges, pomegranate, and other similar fruits that inhibit CYP3A4 during alectinib treatment due to risk for increased toxicity.

  • Store between 15-30ºC in the original package.

Contraindications

  • Patients with known hypersensitivity to alectinib or excipients. 

Other Warnings/Precautions

  • Use with caution in patients who are at risk for gastrointestinal perforation (eg. concomitant use of medications with GI perforation risk, history of diverticulitis, metastases to the GI tract).

  • Use with caution in patients with hepatic impairment or renal impairment.

  • Use with caution in patients who have bradycardia at baseline (< 60 bpm), a history of syncope or arrhythmia, sick sinus syndrome, sinoatrial block, AV block, ischemic heart disease, CHF or who are on medications that lower HR.

  • Vision disorders, asthenia, fatigue and dizziness have been reported.  Patients with these symptoms should use caution when driving or operating machines.

  • Contains lactose; carefully consider use in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.

Pregnancy and Lactation

  • Alectinib is not recommended for use in pregnancy.  Adequate contraception should be used by both sexes during treatment, and for at least 3 months after the last dose if there is any potential for pregnancy.  Female patients who become pregnant while taking alectinib or during the 3 months following the last dose must contact their doctor and be advised of the potential harm to the fetus.

  • Breastfeeding: Not recommended

  • Effects on fertility: Unknown

 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

  • Blood CPK levels; Every 2 weeks for the first month, and as clinically indicated in patients reporting symptoms.

  • Blood pressure and heart rate; Baseline, at each visit, and as clinically indicated.

  • ECG; Baseline and as required to evaluate QTc, AV block.

  • Liver function tests; Baseline, every 2 weeks during the first 3 months of treatment, then at each visit or as clinically indicated; more frequent with abnormal LFTs.

  • Electrolytes, including serum calcium and potassium; Baseline and at each visit.

  • Renal function tests; Baseline and at each visit.

  • Clinical toxicity assessment for bradycardia, photosensitivity, rash, GI effects, edema, fatigue, anemia, myalgia, dizziness, headache, visual disorders, and respiratory problems; at each visit.

  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Outpatient prescription for home administration


 
K - References

Alectinib drug monograph, Cancer Care Ontario.

Ou SI, Ahn JS, De Petris L, et al: Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study. J Clin Oncol, 2015.

Shaw AT, Gandhi L, Gadgeel S, et al: Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol 17:234-42, 2016.

June 2019 Updated emetic risk category, added EAP funding info


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M - Disclaimer

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.