KORSERDU

Treatment with KORSERDU should be initiated by a physician experienced in the use of anticancer therapies. Patients with ER-positive, HER2-negative advanced breast cancer should be selected for treatment with KORSERDU based on the presence of an activating ESR1 mutation in plasma specimens, using a CE marked in vitro diagnostic (IVD) with the corresponding intended purpose.

If the CE-marked IVD is not available, the presence of an activating ESR1 mutation in plasma specimens should be assessed by an alternative validated test. Posology The recommended dose is 345 mg (one 345 mg film-coated tablet), once daily.

The maximum recommended daily dose of KORSERDU is 345 mg. Treatment should continue as long as clinical benefit is observed or until unacceptable toxicity occurs. Missed dose If a dose is missed, it can be taken immediately within 6 hours after the time it is usually taken.

After more than 6 hours, the dose should be skipped for that day. On the next day, KORSERDU should be taken at the usual time. Vomiting If the patient vomits after taking the KORSERDU dose, the patient should not take an additional dose on that day and should resume the usual dosing schedule the next day at the usual time.

8) are provided in Tables 1 and 2: Table 1: KORSERDU dose reduction for adverse reactions KORSERDU dose level Dose and schedule Number and strength of tablets Dose reduction 258 mg once daily Three 86 mg tablets If further dose reduction below 258 mg once daily is required, discontinue KORSERDU.

Table 2:

KORSERDU dose modification guidelines for adverse reactions Severity Dose modification Grade 2 Consider interruption of KORSERDU until recovery to Grade ≤ 1 or baseline. Then resume KORSERDU at the same dose level. Grade 3 KORSERDU should be interrupted until recovery to Grade ≤ 1 or baseline.

The dose should be reduced to 258 mg once daily when resuming therapy. If the Grade 3 toxicity recurs, KORSERDU should be interrupted until recovery to Grade ≤ 1 or baseline. The reduced dose of 258 mg may be resumed at the discretion of the treating physician the patient is benefiting from treatment.

If a Grade 3 or intolerable adverse reaction recurs, KORSERDU should be permanently discontinued. Grade 4 Interrupt KORSERDU until recovery to Grade ≤ 1 or baseline. The dose should be reduced to 258 mg once daily when resuming therapy.

If a Grade 4 or intolerable adverse reaction recurs, permanently discontinue KORSERDU. Use of KORSERDU with CYP3A4 inhibitors Concomitant use of strong or moderate CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered.

If a strong CYP3A4 inhibitor must be used, the elacestrant dose should be reduced to 86 mg once daily with careful monitoring of tolerability. If a moderate CYP3A4 inhibitor must be used, the elacestrant dose should be reduced to 172 mg once daily with careful monitoring of tolerability.

Subsequent dose reduction to 86 mg once daily may be considered with moderate CYP3A4 inhibitors based on tolerability. 2). 5). Use of KORSERDU with CYP3A4 inducers Concomitant use of strong or moderate CYP3A4 inducers should be avoided and an alternative concomitant medicinal product with no or minimal potential to induce CYP3A4 should be considered.

e. e. treatment periods ≤ 3 days separated by at least 2 weeks or 1 week + 5 half-lives of the CYP3A4 inducer, whichever is longer), continue elacestrant without increasing the dose. 2). Special populations Elderly No dose adjustment is required on the basis of patient age.

2). Hepatic impairment No dose adjustment is recommended for patients with mild hepatic impairment (Child-Pugh A). In patients with moderate hepatic impairment (Child-Pugh B), KORSERDU dose should be reduced to 258 mg. 4). Renal impairment No dose adjustment in subjects with renal impairment is necessary.

2). Paediatric population The safety and efficacy of KORSERDU in children from birth to 18 years of age has not been established. No data are available. Method of administration KORSERDU is for oral use. The tablets should be swallowed whole.

They should not be chewed, crushed or split prior to swallowing. Patients should take their dose of KORSERDU at approximately the same time each day. KORSERDU should be administered with a light meal. 2).

Summary of the safety profile The most common (≥ 10%) adverse reactions with KORSERDU were nausea, triglycerides increased, cholesterol increased, vomiting, fatigue, dyspepsia, diarrhoea, calcium decreased, back pain, creatinine increased, arthralgia, sodium decreased, constipation, headache, hot flush, abdominal pain, anaemia, potassium decreased, and alanine aminotransferase increased.

3%), anaemia (2%), back pain (2%), and bone pain (2%). Serious adverse reactions reported in ≥ 1% of patients included nausea, dyspnoea, and thromboembolism (venous). Adverse reactions leading to discontinuation in ≥ 1% of patients included nausea and decreased appetite.

Adverse reactions leading to dose reduction in ≥ 1% of patients included nausea. Adverse reactions leading to dose interruption in ≥ 1% of patients were nausea, abdominal pain, alanine aminotransferase increased, vomiting, rash, bone pain, decreased appetite, aspartate aminotransferase increased, and diarrhoea.

Tabulated list of adverse reactions Adverse reactions described in the list below reflect exposure to elacestrant in 301 patients with breast cancer in three open label studies (RAD1901-005, RAD1901-106, and RAD1901-308) in which patients received elacestrant 400mg once daily as a single agent.

The frequencies of adverse reactions are based on all-cause adverse event frequencies identified in patients exposed to elacestrant at the recommended dose in the target indication, whereas frequencies for changes in laboratory parameters are based on worsening from baseline by at least 1 grade and shifts to ≥ grade 3.

The median duration of treatment was 85 days (range 5 to 1288). The adverse reaction frequencies from clinical trials are based on all-cause adverse event frequencies, where a proportion of the events for an adverse reaction may have other causes than the drug, such as the disease, other medication or unrelated causes.

The following convention is used for the classification of the frequency of an adverse drug reaction (ADR) and is based on the Council for International Organizations of Medical Sciences (CIOMS) guidelines: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1 000 to < 1/100); rare (≥ 1/10 000 to < 1/1 000); very rare (< 1/10 000); not known (cannot be estimated from the available data).

Table 3. Adverse reactions in patients treated with elacestrant monotherapy 345 mg in metastatic breast cancer Elacestrant N=301 Infections and infestations Common Urinary tract infection Very common AnaemiaBlood and lymphatic system disorders Common Lymphocyte count decreased Metabolism and nutrition disorders Very common Decreased appetite Psychiatric Common Insomnia disorders Very common HeadacheNervous system disorder Common Dizziness, Syncope Very common Hot flush*Vascular disorders Uncommon Thromboembolism (venous)* Respiratory, thoracic and mediastinal disorders Common Dyspnoea, Cough* Very common Nausea, Vomiting, Diarrhoea, Constipation, Abdominal pain*, Dyspepsia* Gastrointestinal disorders Common Stomatitis Hepatobiliary disorders Uncommon Acute hepatic failure Skin and subcutaneous tissue disorders Common Rash* Very common Arthralgia, Back painMusculoskeletal and connective tissues disorders Common Pain in extremity, Musculoskeletal chest pain *, Bone pain Very common FatigueGeneral disorders and administration site conditions Common Asthenia Very common Aspartate aminotransferase increased, Triglycerides increased, Cholesterol increased, Alanine aminotransferase increased, Calcium decreased, Creatinine increased, Sodium decreased, Potassium decreased Investigations Common Blood alkaline phosphatase increased *Incidence represents a grouping of similar terms.

ADRs listed by system organ class and by decreasing frequency. Description of selected adverse reactions Nausea Nausea was reported in 35% of patients. 5% of patients. Nausea was generally reported early, with a median time to the first onset 14 days (range: 1 to 490 days).

, over time). 8%) received an antiemetic for the treatment of nausea during the on-treatment period. Elderly In the RAD1901-308 study, 104 patients who received elacestrant were ≥ 65 years and 40 patients were ≥ 75 years. Gastrointestinal disorders were reported more frequently in patients aged ≥ 75 years.

Monitoring of treatment emergent adverse reactions by the treating physician, should include consideration of the patient’s age and comorbidities, when selecting personalised interventions. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard) or search for MHRA Yellow Card in the Google Play or Apple App Store.

Hepatic impairment KORSERDU is metabolised by the liver, and impaired hepatic function can increase the risk for adverse reactions. Therefore, KORSERDU should be used cautiously in patients with hepatic impairment and patients should be regularly and closely monitored for adverse reactions.

2). 2). Concomitant use with CYP3A4 inhibitors Concomitant administration of KORSERDU with strong CYP3A4 inhibitors including, but not limited to: clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole, and grapefruit or grapefruit juice should be avoided.

An alternative concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. 5). Concomitant administration of KORSERDU with moderate CYP3A4 inhibitors including, but not limited to: aprepitant, ciprofloxacin, conivaptan, crizotinib, cyclosporine, diltiazem, dronedarone, erythromycin, fluconazole, fluvoxamine, grapefruit juice, imatinib, isavuconazole, tofisopam and verapamil should be avoided.

An alternative concomitant medicinal product with no or minimal potential to inhibit CYP3A4 should be considered. 5). Concomitant use with CYP3A4 inducers Concomitant administration of KORSERDU with strong CYP3A4 inducers including, but not limited to: phenytoin, rifampicin, carbamazepine and St John’s Wort (Hypericum perforatum) should be avoided.

An alternative concomitant medicinal product with no or minimal potential to induce CYP3A4 should be considered. 5). Concomitant administration of KORSERDU with moderate CYP3A4 inducers including, but not limited to: bosentan, cenobamate, dabrafenib, efavirenz, etravirine, lorlatinib, phenobarbital, primidone, and sotorasib should be avoided.

An alternative concomitant medicinal product with no or minimal potential to induce CYP3A4 should be considered. 5). 8). This should be taken into consideration when prescribing KORSERDU to patients at risk.

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