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Non small cell lung cancer locally advanced or metastatic selpercatinib

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Drug Dose Route
Selpercatinib 160 mg TWICE a day * PO

* For patients less than 50 kg: recommended dosing is 120 mg TWICE a day

Continuous until disease progression or unacceptable toxicity

Drug status:

Selpercatinib is PBS authority opens in a new tab or window

Selpercatinib is available as 40 mg and 80 mg capsules

Cost:
~ $8,060 per month "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, growth factor support etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Continuous treatment
Selpercatinib 160 mg (PO) TWICE a day *

*For patients less than 50 kg: recommended dosing is 120 mg TWICE a day

Continuous until disease progression or unacceptable toxicity

Drug Dose Route
Selpercatinib 160 mg TWICE a day * PO

* For patients less than 50 kg: recommended dosing is 120 mg TWICE a day

Continuous until disease progression or unacceptable toxicity

Drug status:

Selpercatinib is PBS authority opens in a new tab or window

Selpercatinib is available as 40 mg and 80 mg capsules

Cost:
~ $8,060 per month "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, growth factor support etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Continuous treatment
Selpercatinib 160 mg (PO) TWICE a day *

*For patients less than 50 kg: recommended dosing is 120 mg TWICE a day

Continuous until disease progression or unacceptable toxicity

Indications:

  • Locally advanced or metastatic RET fusion positive non small cell lung cancer (NSCLC) 
    • ECOG performance status 0 to 2.
Caution with oral anti-cancer drugs

Select links for information on the safe prescribing, dispensing and administration of orally administered anti-cancer drugs. 

Read more about at COSA guidelines for the safe prescribing, dispensing and administration of systemic cancer therapy opens in a new tab or window and oral anti-cancer therapy opens in a new tab or window
Hypersensitivity

Hypersensitivity reactions may occur, with a majority of reported events observed in patients with NSCLC previously treated with anti-PD-1/PD-L1 immunotherapy. Monitor for fever, rash and arthralgias or myalgias with concurrent decreased platelets or elevated aminotransferases. See dose modifications for further information.
Emetogenicity minimal or low

No routine prophylaxis required. If patients experience nausea and/or vomiting, consider using the low emetogenic risk regimen.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Prolongation of QT interval

QT interval prolongation was reported in patients receiving selpercatinib. Selpercatinib should be used with caution in patients with conditions such as congenital long QT syndrome or acquired long QT syndrome or other clinical conditions that predispose the patient to arrhythmias.

Patients should have a QTcF interval of ≤470 ms and serum electrolytes within the normal range before starting treatment. Hypokalaemia, hypomagnesaemia and hypocalcaemia should be corrected prior to initiating selpercatinib and during treatment.

ECG monitoring is recommended at baseline, again after 1 week of treatment, then at least monthly for the first 6 months and as clinically indicated thereafter. Consider monitoring the QT interval more frequently in patients who require treatment with concomitant medications known to prolong the QT interval. See interactions for further information.

Serum electrolytes should be checked at baseline and again after 1 week of treatment.

See dose modifications section for further information. Read more about drugs that may prolong QTcF interval at crediblemeds.org opens in a new tab or window (registration required).
Hypertension

Pre-existing hypertension should be adequately controlled prior to commencing treatment. It is recommended that the patients' blood pressure be monitored regularly and treated as needed with standard antihypertensive therapy. 

Dose modification or permanent discontinuation may be necessary. See dose modifications for further information.
Haemorrhage

Serious and sometimes fatal haemorrhagic events have been reported with this treatment. Patients should be monitored for signs and symptoms of severe bleeding. Use with caution in patients with risk of bleeding (ie. coagulopathy, concurrent anticoagulant or antiplatelet medications etc.) In the case of bleeding, dose interruptions, adjustments or discontinuation of therapy may be necessary. See dose modifications for further information. 
Pulmonary toxicity

This treatment has been associated with severe, life-threatening or fatal interstitial lung disease (ILD)/pneumonitis. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis, such as dyspnoea, cough, fever, or a radiological abnormality. See dose modifications for further information. 
Oedema, ascites, pleural effusions

Chylous effusions/ascites have been reported in patients receiving selpercatinib.r Consider diagnostic aspiration if there is uncertainty if the effusion is related to treatment toxicity versus disease progression. If chylous effusions are diagnosed, conservative measures (fluid replacement, dietary alteration) or medical therapy (eg. somatostatin analogue) may be considered prior to more invasive measures. See dose modifications for further information. 
Hypothyroidism

Thyroid dysfunction in particular hypothyroidism may occur with this treatment. Monitor for signs and symptoms of thyroid dysfunction and manage as clinically appropriate.
Tumour lysis risk

Assess patient for risk of developing tumour lysis syndrome.

Read more about prevention and management of tumour lysis syndrome.
Wound healing

Impaired wound healing can occur with patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) pathway. Withhold the drug for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery until adequate healing has occured.
Diarrhoea

Antidiarrhoeals (e.g. loperamide) are usually prescribed with this treatment.

Read more about treatment induced diarrhoea
Bloods

FBC, EUC, eGFR, LFTs, calcium, magnesium, phosphate, TFTs at baseline, at least monthly thereafter, and as clinically indicated. 

EUC, calcium and magnesium should be assessed one week after commencing treatment. 
Hepatitis B screening and prophylaxis

The requirement for routine screening for HBsAg and anti-HBc for patients receiving this treatment is unknown. Clinical judgement and individual patient situations should be taken into consideration.

Read more about hepatitis B screening and prophylaxis in cancer patients requiring cytotoxic and/or immunosuppressive therapy
Vaccinations

Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease. Possible suboptimal response to inactivated vaccines.

For more information about vaccinations in people with cancer refer to the Australian Immunisation Handbook opens in a new tab or window.
Fertility, pregnancy and lactation

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. There is a risk of fetal harm in pregnant women. A pregnancy test should be considered prior to initiating treatment in females of reproductive potential if sexually active. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and adequate contraception timeframe should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.

Read more about the impact of cancer treatment on fertility opens in a new tab or window
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) opens in a new tab or window unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.
Selpercatinib dose modifications for adverse events
Dose level Greater than or equal to 50 kg  Less than 50 kg
Recommended starting dose 160 mg orally TWICE a day  120 mg orally TWICE a day 
First dose reduction 120 mg orally TWICE a day  80 mg orally TWICE a day 
Second dose reduction 80 mg orally TWICE a day  40 mg orally TWICE a day 
Third dose reduction 40 mg orally TWICE a day  Not applicable 

Note: Permanently discontinue selpercatinib if unable to tolerate 3 dose reductions. 

Haematological toxicity
ANC x 109/L (pre-treatment blood test)
1.0 to less than 1.5 Refer to local institutional guidelines; it is the view of the expert clinicians that treatment should continue if patient is clinically well
less than 1.0 Delay treatment until recovery
Febrile neutropenia Delay treatment until recovery.
Platelets x 109/L (pre-treatment blood test)
75 to less than 100 The general recommendation is to delay, however if the patient is clinically well it may be appropriate to continue treatment; refer to treating team and/or local institutional guidelines
50 to less than 75 Delay treatment until recovery
less than 50 Withhold until platelet count returns to normal/baseline. Upon recovery, resume selpercatinib with a dose reduction of a minimum of 1 level.  
Kidney dosing recommendations 
eGFR (mL/min/1.73m2) Recommended dose
≥ 15 No dose modification necessary
< 15 This drug has not been studied in patients with end-stage kidney dysfunction
Hepatic impairment 
Hepatic dysfunction (at baseline)
Mild to moderate No dose modification necessary
Severe Commence selpercatinib at a dose of 80 mg TWICE a day.
Hepatotoxicity (during treatment) 
Grade 1 to 2  No dose modification necessary 

Grade 3 to 4 

Withhold selpercatinib until resolution to baseline

Resume selpercatinib at a dose reduced by 2 dose levels

If after 2 weeks selpercatinib is tolerated without recurrent increased ALT or AST increase by 1 dose level

If after 4 weeks selpercatinib is tolerated without recurrent increased ALT or AST, increase to dose taken prior to the onset of Grade 3 or 4 increased ALT or AST.

Permanently discontinue selpercatinib if Grade 3 or 4 ALT or AST increases reoccur despite dose modifications.
QTc interval prolongation
Grade 2 Review concomitant medicines and check electrolytes
Grade 3

Review concomitant medicines and check electrolytes

Withhold selpercatinib for QTcF intervals >500 ms until the QTcF returns to <470 ms or baseline

Resume selpercatinib at next lower dose level
Grade 4 Permanently discontinue selpercatinib if QT prolongation remains uncontrolled after 2 dose reductions or if the patient has signs/symptoms of serious arrhythmia. 
Hypersensitivity reactions (HSR)
All grades 

Withhold selpercatinib until HSR resolves and begin corticosteroids at 1 mg/kg prednisolone or equivalent

Resume selpercatinib at 40mg TWICE a day while continuing steroid treatment

If after at least 7 days, selpercatinib is tolerated without recurrent HSR, incrementally increase the selpercatinib by 1 dose level each week, until the dose taken prior to the onset of HSR is reached

Taper steroid dose after selpercatinib has been tolerated for at least 7 days at the final dose

Permanently discontinue selpercatinib for recurrent HSR.
Hypertension
Grade 3 

Withhold selpercatinib for Grade 3 hypertension that persists despite optimal antihypertensive therapy

Resume selpercatinib at the next lower dose level when hypertension is controlled
Grade 4 

Permanently discontinue selpercatinib if hypertension cannot be resolved with antihypertensive therapy. 
Haemorrhagic events
Grade 3

Withhold selpercatinib until recovery to baseline

Resume selpercatinib at the next lower dose level

If Grade 3 events reoccur following dose modification permanently discontinue selpercatinib

Permanently discontinue selpercatinib for severe events
Grade 4 Permanently discontinue selpercatinib.
Pleural effusions 
Grade 3

Withhold selpercatinib for Grade 3 events until recovery to baseline

Resume selpercatinib at the next lower dose level 

If Grade 3 events reoccur following dose modification permanently discontinue selpercatinib

Permanently discontinue selpercatinib for severe events
Grade 4 Permanently discontinue selpercatinib.
Interstitial lung disease/ Pneumonitis
Grade 2 

Supportive care measures

For Grade 2 events that are persistent or reoccur despite supportive care measures that do not return to baseline or Grade 1 within 7 days, withhold treatment until symptoms resolve to baseline or Grade 1

Resume selpercatinib at the next lower dose level

Permanently discontinue selpercatinib if Grade 2 events reoccur 
Grade 3 or 4 

Permanently discontinue selpercatinib. 
Hypothyroidism
Grade 1 or 2 

No dose modification necessary
Grade 3 or 4 

Withhold selpercatinib until resolution to Grade 1 or baseline

Permanently discontinue selpercatinib based on severity. 
Concomitant use with CYP3A4 inhibitor (e.g. amiodarone, aprepitant, azole antifungals, ritonavir, macrolides, verapamil, grapefruit juice etc.)
Concurrent use with strong CYP3A4 inhibitor Reduce selpercatinib dose by 50%. Monitor for toxicity
If the strong CYP3A4 inhibitor is discontinued Resume the dose of selpercatinib that was used prior to starting the strong CYP3A4 inhibitor 3 to 5 half lives after discontinuing the strong inhibitor.

The drug interactions shown below are not an exhaustive list. For a more comprehensive list and for detailed information on specific drug interactions and clinical management, please refer to the specific drug product information and the following key resources: 

For more information see References & Disclaimer.

Selpercatinib
  Interaction Clinical management
CYP3A4 inhibitors (e.g. aprepitant, azole antifungals, clarithromycin, erythromycin, fluvoxamine, verapamil, grapefruit juice, ritonavir, seville oranges etc.) Increased toxicity of selpercatinib possible due to reduced clearance

Avoid combination or monitor for selpercatinib toxicity

Use with caution if concomitant use with a moderate CYP3A4 inhibitor cannot be avoided

If concomitant use with a strong CYP3A4 inhibitor cannot be avoided, reduce the dose of selpercatinib (see concomitant use with CYP3A4 inhibitor in Dose modifications section) 

If the strong CYP3A4 inhibitor is then discontinued, increase the selpercatinib dose (see concomitant use with CYP3A4 inhibitor in Dose modifications section)
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.) Reduced efficacy of selpercatinib possible due to increased clearance Avoid combination with strong CYP3A4 inducers or monitor for decreased clinical response to selpercatinib
Sensitive CYP3A4 substrates (e.g. alfentanil, midazolam, simvastatin, voriconazole etc.), sensitive CYP2C8 substrates (e.g. enzalutamide, paclitaxel, sorafenib, rosiglitazone, buprenorphine, montelukast etc.) and sensitive P-gp substrates or with a narrow therapeutic index (e.g. dabigatran, colchicine, digoxin etc.) Increased effects/toxicity of these drugs possible due to inhibition of CYP3A4, CYP2C8 or P-gp by selpercatinib resulting in reduced clearance Avoid combination or monitor for increased effect/toxicity of interacting drugs
Drugs that may prolong the QTc interval opens in a new tab or window (e.g. azole antifungals, tricyclic antidepressants, antiarrhythmics etc.) Additive effect with selpercatinib; may lead to torsades de pointes and cardiac arrest

Avoid combination and/or minimise additional risk factors (e.g. correct electrolyte imbalances) and monitor ECG for signs of cardiac arrhythmia
Drugs known to increase the risk of bleeding, including warfarin, direct oral anticoagulants (e.g. apixaban, rivaroxaban, dabigatran etc.), antiplatelet agents (e.g. clopidogrel etc.), NSAIDs (e.g. ibuprofen etc.) Nil drug-drug interaction Although not classified as drug–drug interactions, monitor for signs of bleeding due to reported haemorrhagic events associated with selpercatinib
H2 receptor antagonists (e.g. famotidine, ranitidine etc.), proton pump inhibitors (e.g. omeprazole, pantoprazole, rabeprazole etc.) and antacids (e.g. Gastrogel®, Mylanta® etc.) Selpercatinib efficacy reduced due to decreased absorption at higher gastric pH

H2 receptor antagonists: Take selpercatinib 2 hours before or 10 hours after

Proton pump inhibitors (PPIs): Take selpercatinib with a meal

Antacids (e.g., Gastrogel®, Mylanta®): Take selpercatinib 2 hours before or 2 hours after

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter or address chemical compatibilities related to IV drug preparation and administration. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA opens in a new tab or window and Australian Injectable Drugs Handbook opens in a new tab or window websites for further information.

eviQ is currently updating the way information is presented in the administration section, if you notice any discrepancies please let us know, via feedback@eviq.org.au.

Administration

This is a continuous oral treatment

Pre treatment assessment

Any toxicity grade 2 or greater may require dose reduction, delay or omission of treatment and review by medical officer before commencing treatment.

Anti-cancer drug patient assessment tool prior to each day of treatment.

Selpercatinib requires an ECG at baseline and one week after commencing selpercatinib, then monthly for the first 6 months and as clinically indicated.

Selpercatinib

Administer selpercatinib:
  • orally TWICE a day, at approximately the same time each day
  • to be swallowed whole with a glass of water; do not open, break, crush or chew
  • may be taken with or without food
  • if taking a proton pump inhibitor (PPI), selpercatinib to be administered with a meal. If taking a H2 receptor antagonist, selpercatinib to be administered 2 hours before or 10 hours after. If taking antacids, selpercatinib to be administered 2 hours before or 2 hours after.

Note: missed doses should not be replaced; if a dose is forgotten or vomited, normal dosing should be resumed at the next scheduled dose.

Post administration

Continue safe handling precautions (reproductive risk only) for 7 days after completion of drug(s).

Discharge information

Discharge medications

Selpercatinib capsules​ - with written instructions on how to take them.

Antidiarrhoeals - as/if prescribed.

Antiemetics - as/if prescribed.

Patient information

Ensure patient receives protocol patient information sheet.

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting
Taste and smell alteration

Read more about taste and smell changes
Hypersensitivity reaction

Anaphylaxis and treatment related reactions can occur with this treatment.

Read more about hypersensitivity reaction 

Early (onset days to weeks)
Xerostomia

Xerostomia is defined as the subjective sensation of dryness of the mouth.

Read more about xerostomia
Abdominal pain

Dull ache, cramping or sharp pains are common with some anti-cancer drugs. These are caused by either increased or decreased gastrointestinal motility and can be associated with diarrhoea or constipation.
Constipation
Diarrhoea

Read more about treatment induced diarrhoea
Fatigue

Read more about fatigue
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia
Skin rash

Anti-cancer drugs can cause a number of changes in the skin with maculo-papular rash the most common type of drug-induced skin reaction. 

Read more about skin rash
Fluid retention and oedema

An excess amount of fluid around the cells, tissues or serous cavities of the body, leading to swelling.
Pulmonary toxicity

Monitor patients for interstitial lung disease (ILD) / pneumonitis. Observe for new or worsening respiratory symptoms such as dyspnoea, dry cough, pleural rub, mild crackles, fever, fatigue and a radiological abnormality. 
Haemorrhage
Creatinine elevation

Treatment may cause a reversible, self-limiting increase in the serum creatinine level without having a true effect on kidney function. 
Hepatotoxicity

Anti-cancer drugs administered either alone or in combination with other drugs and/or radiation therapy may cause direct or indirect hepatotoxicity. Hepatic dysfunction can alter the metabolism of some drugs resulting in systemic toxicity.
Hypertension

High blood pressure is commonly associated with many anti-cancer drugs. Pre-existing hypertension should be controlled prior to initiation of drugs capable of causing hypertension.
Hypothyroidism
Neutropenia

Abnormally low levels of neutrophils in the blood. This increases the risk of infection. Any fever or suspicion of infection should be investigated immediately and managed aggressively. 

Read more about immediate management of neutropenic fever
Thrombocytopenia

A reduction in the normal levels of functional platelets, increasing the risk of abnormal bleeding.  

Read more about thrombocytopenia
QT prolongation

This treatment can cause QTc interval prolongation. QTc prolongation can lead to ventricular arrhythmias that may be fatal.

Late (onset weeks to months)
Anaemia

Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. 

Read more about anaemia

eviQ is currently updating the way information is presented in the evidence section to improve usability, consistency and facilitate easier update and maintenance. An updated evidence template is being implemented in a staged approach, first across new protocols, then existing protocols as they are reviewed. Find out more

The evidence supporting this protocol is provided by a randomised phase III trial LIBRETTO-431, which evaluated the safety and efficacy of selpercatinib in patients with unresectable RET fusion-positive non squamous, non small cell lung cancer (NSCLC) who had not previously received systemic treatment for metastatic disease. Patients with brain metastases were eligible if asymptomatic or neurologically stable for 2 weeks prior to randomisation.r

Efficacy and safety was established in the LIBRETTO–001 trial which demonstrated efficacy in patients with advanced RET fusion–positive NSCLC in a phase I/II trial.r

Between March 2020 to August 2022, 261 patients with RET fusion–positive advanced NSCLC were randomly assigned to receive either selpercatinib 160 mg twice daily in continuous 21 day cycles (n=158) or pemetrexed 500 mg/m2 along with the investigator’s choice of platinum therapy, [carboplatin AUC 5 (maximum dose 750 mg), or cisplatin 75 mg/m2] for 4 cycles and pembrolizumab 200 mg (n=98), for up to 35 cycles every 21 days. Pemetrexed could be continued with or without pembrolizumab.r

Primary endpoint was progression free survival (PFS) in the intent to treat (ITT) population. Secondary endpoints were overall survival (OS) in the ITT population, PFS according to investigator assessment in both the ITT pembrolizumab population and the overall ITT population, as well as the percentage of patients with a response, the duration of response (DoR), and central nervous system (CNS) response.r

Efficacy

After a median follow up time of 19 months, median PFS was 24.8 months (95% confidence interval [CI], 16.9 to not estimable [NE]) with selpercatinib and 11.2 months (95% CI, 8.8 to 16.8) with control treatment (hazard ratio [HR] for progression or death, 0.46; 95% CI, 0.31 to 0.70; P<0.001). OS data was not yet mature at the time of reporting. The percentage of patients with an objective response was 84% (95% CI, 76 to 90) with selpercatinib and 65% (95% CI, 54 to 75) with the control treatment arms.r

The 12-month cumulative incidence of central nervous system (CNS) progression, with adjustment for the competing risks of non-CNS progression and death, was 6% (95% CI, 2 to 11) in the selpercatinib group and 20% (95% CI, 11 to 31) in the control group.r

Among the patients with measurable brain metastases at baseline, intracranial response occurred in 82% (95% CI, 57 to 96) of those in the selpercatinib group and 58% (95% CI, 28 to 85) of those in the control group.r

Kaplan-Meier curves PFSr

© N Engl J Med 2023

At approximately 21 months of median follow-up time, OS data remained immature with more than 76% of the patients in each group still alive. Of the patients assigned to the control group who stopped receiving control treatment or discontinued participation, approximately 60% crossed over to receive selpercatinib within the trial, and an additional 15% went on to receive a selective RET inhibitor outside the trial.r 

Kaplan-Meier curves immature OSr

© N Engl J Med 2023

Summary of endpointsr 

© N Engl J Med 2023

Toxicity 

The most common Grade 3 and above adverse events (AE) in the selpercatinib group were AST and ALT elevation, hypertension, QT prolongation, oedema, fatigue and thrombocytopaenia. 

AE leading to permanent discontinuation of treatment were reported in 10% of the patients in the selpercatinib group and 2% of the patients in the control group. Fatal AEs that occurred during participation in the trial occurred in 7 patients (4.4%) in the selpercatinib group and none of the patients in the control group; the deaths in 2 of 7 patients were judged by the investigators to be related to selpercatinib.r 

Summary of adverse eventsr


© N Engl J Med 2023

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Version 1

Date Summary of changes
18/10/2024

New protocol reviewed at the Respiratory Reference Committee Meeting.
07/03/2025 Protocol approved 14/02/2025 and published 07/03/2025. Review in 1 year.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/4471

13 Jun 2025