DORSET MEDICINES ADVISORY GROUP

COMMISSIONING STATEMENT ON THE USE OF ERYTHROPOIESIS-STIMULATING AGENTS (EPOETIN AND DARBOPOETIN) FOR TREATING CANCER TREATMENT- INDUCED ANAEMIA

SUMMARY NHS Dorset Clinical Commissioning Group recommends the use of erythropoiesis-stimulating agents (epoetin and darbepoetin) for cancer treatment- induced anaemia in accordance with NICE TA 323.

Erythropoietin is a growth factor that primarily stimulates red cell production. In patients with cancer, deficiency and a reduced response of erythroid progenitor cells to endogenous erythropoietin both contribute significantly towards anaemia. , beta, theta and zeta and darbopoetin are recombinant human erythropoietin analogues used to shorten the period of symptomatic anaemia in people having cytotoxic chemotherapy. Epoetins are recommended for use when haemoglobin concentrations are 100 g/litre or lower, and target values up to 120 g/litre.

Epoetin alfa (Eprex®, Janssen-Cilag, Binocrit, Sandoz), has a UK marketing authorisation for the 'treatment of anaemia and reduction of transfusion requirements in adult patients receiving chemotherapy for solid tumours, malignant lymphoma or multiple myeloma, who are at risk of transfusion as assessed by the patient's general status '. They are administered by subcutaneous injection at a recommended initial dose of 150 units/kg body weight 3 times weekly or 450 units/kg body weight once a week.

Epoetin beta (NeoRecormon®, Roche Products) has a UK marketing authorisation for BACKGROUND the 'treatment of symptomatic anaemia in adult patients with non-myeloid malignancies who are receiving chemotherapy'. It is administered by subcutaneous injection at a recommended initial dose of 450 units/kg body weight once a week or in divided doses 3 to 7 times a week.

Epoetin theta (Eporatio®, Teva UK) has a UK marketing authorisation for the 'treatment of symptomatic anaemia in adult patients with non-myeloid malignancies who are receiving chemotherapy'. It is administered by subcutaneous injection at a recommended initial dose of 20,000 units once a week.

Epoetin zeta (Retacrit®, Hospira UK) has a UK marketing authorisation for the 'treatment of anaemia and reduction of transfusion requirements in adult patients receiving chemotherapy for solid tumours, malignant lymphoma or multiple myeloma, who are at risk of transfusion as assessed by the patient's general status’. It is administered by subcutaneous injection at a recommended initial dose of 150 units/kg bodyweight 3 times weekly or 450 units/kg body weight once a week.

Binocrit® and Retacrit® are biosimilar medicines referenced to Eprex®.

Darbepoetin alfa (Aranesp®, Amgen) is a hyperglycosylated derivative of epoetin that stimulates erythropoiesis by the same mechanism as the endogenous hormone. Aranesp® has a UK marketing authorisation for the 'treatment of symptomatic anaemia in adult cancer patients with non-myeloid malignancies who are receiving chemotherapy'. It is administered by subcutaneous injection at a recommended initial dose of 500 micrograms (6.75 micrograms/kg body weight) once every 3 weeks or 2.25 micrograms/kg body weight once a week.

Erythropoiesis-stimulating agents are the subjects of a NICE Health Technology RELEVANT NICE Appraisal published in November 2014 - NICE TA323 (Erythropoiesis-stimulating GUIDANCE agents (epoetin and darbepoetin) for treating anaemia in people with cancer having chemotherapy (including review of TA142).

FORMULARY Red STATUS

PbR STATUS Included in PbR tariff

This TA has the potential to extend the use and hence cost of erythropoietin analogues for cancer treatment- induced anaemia, as it removes the conditions for treatment (only be considered in combination with intravenous iron, for women COMMISSIONING receiving platinum-based chemotherapy for ovarian cancer with symptomatic IMPLICATIONS anaemia with a haemoglobin concentration of 8 g/100 mL or lower, those who cannot be given blood transfusions and who have profound cancer treatment- related anaemia that is likely to have an impact on survival).

RELEVANT CLINICAL COMMISSIONING Cancer and End of Life PROGRAMME The aim of treatment is to relieve symptoms of anaemia, and in patients with chronic kidney disease to avoid the need for blood transfusion; the haemoglobin concentration should not be increased beyond that which provides adequate control of symptoms of anaemia (in some patients, this may be achieved at concentrations lower than the recommended range). PATIENT PATHWAY

IMPLICATIONS Treatment with ESA can modestly reduce blood transfusion exposure and improve HRQoL in selected cancer patients, especially in those treated with nephrotoxic platinum compounds. The maximum improvement in fatigue and HRQoL occurs between Hb 110 and 120 g/L.

Efficacy See the NICE TA for underpinning evidence: The NICE Technology Appraisal TA323 (Erythropoiesis-stimulating agents (epoetin SUMMARY OF and darbepoetin) for treating anaemia in people with cancer having chemotherapy EVIDENCE TO (including review of TA142) states that they are recommended, within their SUPPORT marketing authorisations, as options for treating anaemia in people with cancer who FORMULARY are having chemotherapy. STATUS If different erythropoiesis-stimulating agents are equally suitable, the product with the lowest acquisition cost for the course of treatment should be used.

Safety For specific details of the adverse effects of each drug see the summary of product characteristics (SPCs).

Note MHRA safety advice: —haemoglobin concentration (Dec 2007): Overcorrection of haemoglobin concentration in patients with chronic kidney disease may increase the risk of death and serious cardiovascular events, and in patients with cancer may increase the risk of thrombosis and related complications: •patients should not be treated with erythropoietins for the licensed indications unless symptoms of anaemia are present; •the haemoglobin concentration should be maintained within the range 10–12 g/100 mL; •haemoglobin concentrations higher than 12 g/100 mL should be avoided.

Erythropoietins—tumour progression and survival in patients with cancer (July 2008:) Clinical trial data show an unexplained excess mortality and increased risk of tumour progression in patients with anaemia associated with cancer who have been treated with erythropoietins. Many of these trials used erythropoietins outside of the licensed indications (i.e. overcorrected haemoglobin concentration or given to patients who have not received chemotherapy): •erythropoietins licensed for the treatment of symptomatic anaemia associated with cancer, are licensed only for patients who are receiving chemotherapy; •the decision to use erythropoietins should be based on an assessment of the benefits and risks for individual patients; blood transfusion may be the preferred treatment for anaemia associated with cancer chemotherapy, particularly in those with a good cancer prognosis.

Dose Av. dose Cost/vial Cost/week No Cost/patient (assuming 70 (£) (£) weeks (£) Kg weight) Tx Epoetin alfa 150 units/kg 10,000 units 55.31 156.93 18 2824.74 (Eprex) 3 x weekly Epoetin alfa 150 units/kg 10,000 units 43.27 129.81 18 2336.58 (Binocrit) 3 x weekly 450 units/kg 30,000 units 210.43 210.43 18 3787.74 ASSESSMENT OF weekly COST IMPLICATIONS Epoetin 20,000 units 20,000 units 119.84 119.84 18 2157.12 theta weekly Epoetin zeta 150 units/kg 10,000 units 56.57 169.71 18 3054.78 3 x weekly Darbopoetin 2.25mcg/kg 150mcg 220.22 220.22 18 3963.96 alfa weekly

Costs of products may vary in different settings because of negotiated procurement discounts.

National Institute for Health and Care Excellence. Technology Appraisal Guidance 323 Erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating anaemia in people with cancer having chemotherapy (including review of TA142). London: NICE; November 2014. Accessed on 4th December 2014 via http://www.nice.org.uk/guidance/TA323

Summary of Product Characteristics. Selincro 18mg film-coated tablets. Lundbeck Ltd. Accessed on 4th December 2014 via www.medicines.org.uk/emc

British Medical Association and Royal Pharmaceutical Society of Great Britain. British National Formulary. BMJ Group and RPS Publishing. London; December 2014.

Summary of Product Characteristics. Aranesp. Amgen Ltd. Accessed on 22nd December via www.medicines.org.uk/emc

REFERENCES Summary of Product Characteristics. Eprex. Janssen-Cilag Limited. Accessed on 22nd December via www.medicines.org.uk/emc

Summary of Product Characteristics. Binocrit. Sandoz Limited. Accessed on 22nd December via www.medicines.org.uk/emc

Summary of Product Characteristics. Neorecormon. Roche Products Limited. Accessed on 22nd December via www.medicines.org.uk/emc

Summary of Product Characteristics. Eporatio. Ratiopharm UK. Accessed on 22nd December via www.medicines.org.uk/emc

Summary of Product Characteristics. Retacrit. Hospira UK Ltd. Accessed on 22nd December via www.medicines.org.uk/emc

Date 22nd December 2014

Review date 22nd December 2016

Contact for this Katie Taylor, Locality Pharmacist Dorset CCG [email protected] Policy