SELP

CONTINUOUS TREATMENT

Until clinically meaningful disease progression* or unacceptable toxicity

(*Refer to CADTH recommendations and Drilon et al)

• Also refer to CCO Antiemetic Recommendations.
   

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.

Other Supportive Care:

• Consider appropriate prophylaxis including hydration for patients at risk of tumour lysis syndrome (e.g. rapidly growing tumors, high tumor burden, renal dysfunction, or dehydration).

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

Confirm RET gene fusion or mutation using a validated test before initiation.

Hypertension should be well-controlled prior to initiation of treatment.

Patients must have a QTcF interval of ≤ 470 ms and serum electrolytes within normal range before starting treatment.

Hold selpercatinib for > 7 days prior to elective surgery. Do not administer for > 2 weeks following major surgery and until adequate wound healing.

Refer to Interactions section for dosing recommendations when co-administered with CYP3A4 inhibitors.

Limited safety data are available in patients with severe hepatic impairment; monitor ALT and AST more frequently as clinically indicated.

No dosage adjustment is necessary in patients with mild, moderate or severe renal impairment. Selpercatinib is not recommended in patients with end-stage renal disease.

No overall differences in safety or efficacy observed between patients  ≥ 65 years of age and younger patients.

Refer to selpercatinib drug monograph(s) for additional details of adverse effects.
 

Refer to selpercatinib drug monograph(s) for additional details.

• Avoid concomitant use with strong or moderate CYP3A4 inhibitors. If unavoidable, ↓ selpercatinib dose and perform ECG more frequently. Refer to table below.
• Avoid concomitant use with strong or moderate CYP3A4 inducers.
• Avoid concomitant use with sensitive CYP3A4 or CYP2C8 substrates. If unavoidable, ↓ substrate dose as per product monograph.
• Avoid coadministration with PPIs. If unavoidable, administer selpercatinib with food.
• Avoid coadministration with H2 receptor antagonists. If unavoidable, administer selpercatinib 2 hours before or 10 hours after H2 receptor antagonist.
• Avoid coadministration with antacids. If unavoidable, administer selpercatinib 2 hours before or 2 hours after antacids.
• Avoid concomitant use with BCRP or P-gp substrates with a narrow therapeutic range. If unavoidable, follow recommendations for BCRP or P-gp substrates as per product monograph.
• Avoid concomitant use with drugs that may prolong QT. If unavoidable, monitor ECG and electrolytes.
• Avoid concomitant use with drugs that disrupt electrolyte levels, if possible.
• Avoid concomitant use with drugs that reduce heart rate.
   

Dose Modification when Co-administered with CYP3A4 Inhibitors

_{*After the inhibitor has been discontinued for 3 to 5 elimination half-lives of the inhibitor, resume selpercatinib at the dose taken before starting the CYP3A4 inhibitor.}

There is no data on the safety of concomitant use of CYP3A inhibitors in patients whose dose was previously reduced due to adverse effects  

Refer to selpercatinib drug monograph(s) for additional details.

Administration

• Administer selpercatinib with or without food. Refer to Interaction section when given concomitantly with PPIs, H2 receptor antagonists, or antacids.
• Capsules should be swallowed whole with a glass of water and not opened, crushed, or chewed.
• Grapefruit, starfruit, Seville oranges, their juices or products should be avoided during selpercatinib treatment.
• If a dose is missed, the dose may be taken if there are > 6 hours until the next dose. If there are < 6 hours until the next dose, the dose should be skipped and the next dose should be taken at the scheduled time. Patients should not take 2 doses at the same time to make up for a missed dose.
• If the patient vomits after taking a dose, an additional dose should not be taken. The next dose should be continued as scheduled.
• Store at room temperature (15° to 30°C).

Contraindications

• Patients who have a hypersensitivity to this drug or any of its components
   

Other Warnings/Precautions

• Avoid use of selpercatinib in patients with conditions that may increase the risk of experiencing torsade de pointes. 
• Patients should exercise caution when driving or operating a vehicle or potentially dangerous machinery as dizziness has been reported.
   

Pregnancy/Lactation

• This regimen is not recommended for use 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.
• Breastfeeding is not recommended 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: 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

Outpatient prescription for home administration

CADTH reimbursement recommendation: selpercatinib (metastatic RET fusion-positive non-small cell lung cancer). May 2022.

Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of selpercatinib in RET fusion-positive non-small-cell lung cancer. N Engl J Med 2020;383(9):813-24.

Selpercatinib drug monograph. Ontario Health (Cancer Care Ontario).