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A - Regimen Name

APAL Regimen
apalutamide


Disease Site
Genitourinary - Prostate

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

For the treatment of patients with non-metastatic castration-resistant prostate cancer (NM-CRPC) in combination with a gonadotropin-releasing hormone (GnRH) antagonist (if patient had not received bilateral orchiectomy).

 
B - Drug Regimen

  • Patients should also receive a gonadotropin-releasing hormone (GnRH) analog unless they have had a bilateral orchiectomy.

apalutamide
240 mg /day PO Daily
(This drug is not currently publicly funded for this regimen and intent)
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C - Cycle Frequency

CONTINUOUS TREATMENT

Until disease progression or unacceptable toxicity

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Not applicable

Patients should be assessed for the risk of fracture and fall and treated to prevent clinical fractures according to guidelines, with consideration given to use of bone-targeted agents.

 
E - Dose Modifications

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

Dosage with toxicity

Dose Level Apalutamide Dose (mg/day)
0 240
-1 180
-2 120
-3 Discontinue 

 

Toxicity Action
Intolerable or ≥ Grade 3 Hold until recover to ≤ Grade 1, resume at the same dose or at ↓ 1 dose level.
If the toxicity recurs at ≥ Grade 3, ↓ 1 dose level.

Seizure

Permanently discontinue.



Hepatic Impairment

Hepatic Impairment Action
Mild or moderate No adjustment required
Severe No data

Renal Impairment

Renal Impairment Action
 Mild to moderate (CrCL ≥ 30 mL/min) No adjustment required
Severe (CrCL ≤ 29 mL/min) No data

Dosage in the Elderly

No dose adjustment is necessary for elderly patients.  Patients ≥ 65 years treated with apalutamide experienced higher toxicity and lower tolerance. Monitor elderly patients more closely for toxicity and adjust dose when needed.

 

Dosage based on Ethnicity:

There is no clinically relevant difference in exposure between White (Caucasian or Hispanic or Latino), Black (of African heritage or African American), Asian (non-Japanese), or Japanese patients. No dose adjustments are necessary.


 
F - Adverse Effects

Refer to apalutamide 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

  • ↑ Cholesterol
  • Anemia
  • Hyperglycemia
  • Myelosuppression
  • Fatigue
  • ↑ K
  • Hypertension
  • Rash
  • Diarrhea
  • Nausea
  • Anorexia, weight loss
  • Arthralgia
  • Falls
  • Androgen deprivation symptoms
  • Fracture
  • Edema

 

  • Seizure
  • Arterial thromboembolism
  • Cardiotoxicity
  • QT interval prolonged
  • Hypothyroidism
 
G - Interactions

Refer to apalutamide drug monograph(s) for additional details


  • Consider dose adjustment for apalutamide based on tolerability with co-administration of strong CYP2C8 or CYP3A4 inhibitors.

  • Avoid co-administration with CYP3A4, CYP2C19 and CYP2C9 substrates. Substitute for these medications when possible or evaluate for loss of activity if medication is continued.

  • Exercise caution with co-administration with P-gp, BCRP, OATP1B1 and UGT substrates. Evaluate for loss of activity if medication is continued (especially thyroxine).

 
H - Drug Administration and Special Precautions

Refer to apalutamide drug monograph(s) for additional details


Administration

  • Tablets should be swallowed whole with a glass of water.

  • Tables can be taken with or without food.

  • Take the dose at around the same time each day.

  • A missed dose should be taken as soon as possible on the same day with a return to the normal schedule on the following day. The patient should not take extra tablets to make up the missed dose.

  • Store at 15°C to 30°C, in the original package to protect from light and moisture.

  • If tablets are provided in a bottle, do not remove the silica gel desiccant from the bottle.


Contraindications

  • Patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

  • Women who are or may become pregnant.
     

Precautions

  • Exercise caution in patients with:

    • Cardiac disorders. Patients with clinically significant cardiovascular disease in the past 6 months including severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events or clinically significant ventricular arrhythmias were excluded from clinically trials.

    • Seizures. Patients with a history of seizures or predisposing factors for seizures were excluded from clinical studies; patients on medications known to lower seizure threshold were prohibited while receiving apalutamide.

    • AT prolongation, risk factors for Torsade de pointes, or on medications known to prolong QTc.

 

Pregnancy & Lactation

  • Apalutamide is not recommended for use in pregnancy. Adequate contraception should be used by both sexes of childbearing potential during treatment, and for at least 3 months after the last dose.

  • Apalutamide is not indicated for use in females. There are no data on the presence of apalutamide or its metabolites in human milk.

  • Fertility effects: Yes

 
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

  • ECG; Baseline and as clinically indicated; more frequent in patients at risk of QTc increase

  • INR; If warfarin cannot be discontinued; baseline and during apalutamide treatment

  • TSH; Baseline and as clinically indicated

  • Clinical toxicity assessment for androgen withdrawal effects, fatigue, infection, active cardiac disease, seizure, dermatologic toxicity and risk of fracture and falls; At each visit

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


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K - References

Apalutamide drug monograph, Cancer Care Ontario.

Smith MR, Saad F, Chowdhury S, et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N Engl J Med 2018;378:1408-18.

 

May 2019 Updated emetic risk category


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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.