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Etirinotecan Pegol for Metastatic Breast Cancer - Second Or Subsequent Line

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Etirinotecan Pegol for Metastatic Breast Cancer - Second Or Subsequent Line Horizon Scanning Centre March 2014 Etirinotecan pegol for metastatic breast cancer - second or subsequent line SUMMARY NIHR HSC ID: 5971 Etirinotecan pegol is intended to be used as a second or subsequent line therapy for the treatment of metastatic breast cancer. If licenced, it would offer an additional treatment option for patients with this disease who have previously been treated with, or are intolerant to first line adjuvant or neo- adjuvant chemotherapy, and who currently have few well tolerated, effective treatment options remaining. Etirinotecan pegol is the PEGylated form of This briefing is irinotecan, that is designed to provide continuous exposure to SN38 (the based on active moiety of irinotecan), while reducing the toxicities associated with information excessively high irinotecan and SN38 plasma concentrations that occur with available at the time direct administration. Etirinotecan pegol is not currently licenced in the EU for of research and a any indication. Etirinotecan pegol’s first generation predecessor irinotecan is limited literature licenced (as combination therapy) for the treatment of advanced and search. It is not metastatic colorectal cancer. intended to be a definitive statement Breast cancer accounts for 30% of all cancers in UK women. In 2011, there on the safety, were 41,826 new cases of breast cancer in England. Breast cancer efficacy or incidence is strongly related to age. An estimated 5% of patients present with effectiveness of the metastatic breast cancer, and approximately 30% of people who present with health technology localised breast cancer will later develop metastatic breast cancer. It is covered and should estimated that in the UK, around 36,000 women are living with metastatic not be used for breast cancer, with 12,000 being in the last year of life. In 2012, there were commercial 10,373 deaths due to breast cancer in England. purposes or commissioning For patients with metastatic breast cancer, the aims of treatment are to without additional improve quality of life and to prolong survival, without necessarily offering a information. realistic hope of cure. Current treatment options include: endocrine therapy, chemotherapy, bone-directed agents, targeted biological agents for HER2- positive disease, palliative radiotherapy, and surgery or radical radiotherapy for limited metastatic presentations. Etirinotecan pegol is currently in one phase III clinical trial comparing its effect on overall survival against treatment with physician’s choice of therapy (eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel or nab-paclitaxel). This trial is expected to complete in December 2014. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. NIHR Horizon Scanning Centre, University of Birmingham Email: [email protected] Web: http://www.hsc.nihr.ac.uk NIHR Horizon Scanning Centre TARGET GROUP • Breast cancer: locally advanced or metastatic – second and subsequent line. TECHNOLOGY DESCRIPTION Etirinotecan pegol (NKTR-102) is the PEGylated form of irinotecan, a topoisomerase-I inhibitor derived from camptothecin. It consists of the topoisomerase-I inhibitor irinotecan bound to a proprietary polyethylene glycol core by a biodegradable linker. The linker slowly hydrolyses in vivo to release SN38, the active moiety of irinotecan. The drug is designed to provide continuous exposure to SN38 while reducing the toxicities associated with excessively high irinotecan and SN38 plasma concentrations reported in patients who receive irinotecan directly. In the phase III trial, 145mg/m2 of etirinotecan pegol was delivered as a 90 minute intravenous (IV) infusion on day 1 of each 21 day treatment cycle until disease progression or unacceptable toxicity1. Etirinotecan pegol does not currently have Marketing Authorisation in the EU for any indication. However its first generation predecessor, irinotecan, is licenced for the treatment of: • Advanced colorectal cancer (combination with 5-fluorouracil and folinic acid in patients without prior chemotherapy for advanced disease, or as a single agent in patients who have failed an established 5-fluorouracil containing treatment regimen). • Epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer after failure of irinotecan-including cytotoxic therapy (in combination with cetuximab). • Metastatic carcinoma of the colon or rectum (in combination with 5-fluorouracil, folinic acid and bevacizumab). Very common (>10%) adverse effects of irinotecan when used for its licenced indications include: severe diarrhoea, neutropenia, anaemia, thrombocytopenia and reversible alopecia2. Etirinotecan pegol is currently in phase II clinical trials for colorectal, ovarian, non- small cell lung, small cell lung cancers and high grade glioma. INNOVATION and/or ADVANTAGES If licensed, etirinotecan pegol will offer an additional treatment option for patients with locally recurrent or metastatic breast cancer who have previously been treated with, or are intolerant to first line adjuvant or neo-adjuvant chemotherapy, a patient group who currently have few well-tolerated effective therapies available. DEVELOPER Nektar Therapeutics. AVAILABILITY, LAUNCH OR MARKETING Etirinotecan pegol is currently in phase III clinical trials. 2 NIHR Horizon Scanning Centre PATIENT GROUP BACKGROUND Breast cancer arises from the tissues of the breast duct or the lobules of the breast; metastatic disease represents spread to distant sites of the body. The most common sites for metastases include the lymph nodes, bone, liver, lungs and brain3,4. Once breast cancer becomes metastatic it is rarely, if ever, curable5. NHS or GOVERNMENT PRIORITY AREA This topic is relevant to: • Improving Outcomes: A Strategy for Cancer (2011). • NHS England. 2013/14 NHS Standard Contract for Cancer: Chemotherapy (Adult). B15/S/a. • NHS England. 2013/14 NHS Standard Contract for Cancer: Radiotherapy (All Ages). B01/S/a. CLINICAL NEED and BURDEN OF DISEASE Breast cancer is the most common cancer in UK, accounting for 30% of all cancers in women6. In England, in 2011, there were 41,826 new cases of breast cancer in both men and women and 41,523 cases in women alone (representing 124.8 cases per 100,000 population)7. In 2012, there were 10,373 deaths from breast cancer registered in England and Wales (ICD C50), as well as 177,514 admissions for malignant neoplasm of the breast (ICD C50) in England, which resulted in 109,365 bed days and 180,595 finished consultant episodes 8,9. Breast cancer risk is strongly related to age, with 81% of cases occurring in women aged over 50 years, and while the incidence of breast cancer is highest in those from higher socioeconomic groups10,11, survival is lowest in those from lower socioeconomic groups. This pattern persists even after allowing for the higher overall premature all-cause mortality observed in lower socioeconomic groups compared to the higher socioeconomic groups12. An estimated 5% of patients present with metastatic breast cancer, and approximately 30% of people who present with localised breast cancer will later develop metastatic breast cancer13. Women with metastatic disease have an average survival of about 2 years5. Cases of secondary breast cancer, which occur after an initial diagnosis of primary breast cancer, are not recorded nationally, but it is estimated that in the UK, around 36,000 women are living with progressive disease, with 12,000 being in the last year of life14,15. PATIENT PATHWAY RELEVANT GUIDANCE NICE Guidance • NICE technology appraisal in development. Breast cancer (early) - intrabeam radiosurgery system [ID618]. Expected November 201416. • NICE technology appraisal in development. Breast cancer (HER2 positive, unresectable) - trastuzumab emtansine (after trastuzumab & taxane) [ID603]. Expected August 201417. 3 NIHR Horizon Scanning Centre • NICE technology appraisal. Bevacizumab in combination with capecitabine for the first line treatment of metastatic breast cancer (TA263). August 201218. • NICE technology appraisal. Lapatinib or trastuzumab in combination with an aromatase inhibitor for the first-line treatment of metastatic hormone receptor positive breast cancer which over-expresses HER2 (TA257). June 201219. • NICE technology appraisal. Eribulin for the treatment of locally advanced or metastatic breast cancer (TA250). April 201220. • NICE technology appraisal. Fulvestrant for the treatment of locally advanced or metastatic breast cancer (TA239). London. December 201121. • NICE technology appraisal. Bevacizumab in combination with a taxane for the first line treatment of metastatic breast cancer (TA214). London. February 201122. • NICE clinical guideline. Advanced breast cancer – diagnosis and treatment (CG81). February 200923. • NICE clinical guideline. Familial breast cancer: Classification and care of people at risk of familial breast cancer and management of breast cancer and related risks in people with a family history of breast cancer (CG164). June 201324. • NICE quality standard. Breast cancer quality standard (QS12). September 201125. Other Guidance • European Society for Medical Oncology. Locally recurrent or metastatic breast cancer. Clinical practice guidelines for diagnosis, treatment and follow-up. 201026. • SIGN. Management of breast cancer in women. 200527. • Cancer Services Collaborative Improvement Partnership.
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