Eribulin for locally advanced or metastatic breast cancer third line; monotherapy

Transcription

1 Eribulin for locally advanced or metastatic breast cancer third line; monotherapy April 2009 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The Research Programme is part of the National Institute for Health Research

2 Eribulin for locally advanced or metastatic breast cancer third line; monotherapy Target group Breast cancer: locally advanced or metastatic third line; monotherapy. Technology description Eribulin (E7389; ER086526; Eribulin mesylate) is a synthetic analogue of halichondrin. B. Halichondrins have been isolated from a variety of marine sponges, including Halichondria okadai, Axinella sp., Phakellia carteri, and Lissodendoryx sp., and exhibit antitumour activity through the inhibition of tubulin polymerisation. The destabilisation of tubulin polymers disrupts the assembly and formation of microtubules, which in turn arrests cancer cell division. Eribulin is administered at 1.4mg/m 2 intravenously (IV) on days 1 and 8 of a 21 day cycle. Eribulin is in phase II clinical trials for non-small cell lung cancer, prostate cancer and soft tissue sarcoma. Innovation and/or advantages Eribulin is a new class of drug with a novel mechanism of action, which could improve patient outcomes. Developer Eisai Ltd. Availability, launch or marketing dates, and licensing plans: In phase III clinical trials NHS or Government priority area This topic is relevant to the NHS Cancer Plan (2000) and Cancer Reform Strategy (2007). Relevant guidance NICE Technology Appraisals NICE technology appraisal in development. Ixabepilone for locally advanced or metastatic breast cancer. Suspended April th wave 1. NICE technology appraisal in development. Lapatinib for the treatment of advanced or metastatic breast cancer. 13 th wave 2. NICE technology appraisal. Breast cancer (advanced & metastatic) bevacizumab. Terminated NICE technology appraisal. Gemcitabine for the treatment of metastatic breast cancer (review planned for January 2010) 4. NICE technology appraisal. Capecitabine for the treatment of locally advanced or metastatic breast cancer NICE technology appraisal. Vinorelbine for the treatment of advanced breast cancer NICE technology appraisal. Taxanes for the treatment of breast cancer (review) NICE Clinical Guidelines 2

3 NICE clinical guideline in development. Advanced breast cancer diagnosis and treatment. Expected 2009 (9 th wave) 8. NICE clinical guideline. Familial breast cancer (review planned 2010) 9. NICE cancer service guidance. Improving outcomes in breast cancer Other Guidelines SIGN. Management of breast cancer in women Clinical need and burden of disease Breast cancer is the most common malignancy affecting women in the UK. There were 40,849 women newly diagnosed with breast cancer in England and Wales during and in 2006 there were 10,984 registered deaths 13. Between 16-20% of women (an estimated 6,536 to 8,170) presenting with breast cancer have advanced disease with distant metastases and in 2002 NICE estimated that around 50% of those presenting with early or localised breast cancer will eventually develop metastatic breast cancer 14. Existing comparators and treatments For patients with metastatic disease the aim of treatment is to ameliorate symptoms, maintain quality of life and prolong survival. Chemotherapeutic resistance in women with prior exposure to anthracyclines and taxanes is a major therapeutic challenge. Current treatment options include: First line chemotherapy: usually an anthracycline based regimen or a combination of cyclophosphamide, methotrexate and fluorouracil. Following disease progression on an anthracycline, other chemotherapy options include single-agent or combination taxanes, capecitabine, vinorelbine, lapatinib and gemcitabine. Efficacy and safety Trial NCT : eribulin vs capecitabine; NCT (EMBRACE) 16 : eribulin phase III. vs physician s treatment choice; phase III. Sponsor Eisai Medical Research Inc. Eisai Medical Research Inc. Status Ongoing. Ongoing. Location Worldwide. Worldwide (inc UK). Design Randomised; open label. Randomised; open label. Participants n=1,100; adults; breast cancer; locally n=630; adults; breast cancer; locally and advanced or metastatic; received up to 3 advanced or metastatic; received at least 2 schedule prior chemotherapy regimens, and no more (not more than 5) prior chemotherapy than 2 prior regimens for advanced disease regimens, and no more than 2 prior (must have included an anthracycline and a regimens for advanced disease (must have taxane). included an anthracycline and a taxane). Randomised to eribulin 1.4mg/m 2 IV on days Randomised to eribulin 1.4mg/m 2 IV on 1, 8 and then every 21 days, or oral days 1, 8 and then every 21 days or capecitabine 2.5g/m 2 per day in 2 equal doses physician s treatment of choice. on days 1, 14 and then every 21 days. Follow-up 1, 2 and 3 year survival. Overall survival until study endpoint reached. Primary Overall survival (OS); progression-free OS; PFS. outcomes survival (PFS). Secondary Quality of Life (QoL); objective tumour Adverse events, concomitant medications, 3

4 outcomes Expected reporting date response; duration of response; pain laboratory assessments, ECGs, objective intensity; analgesic consumption; safety. tumour response, duration of response. Estimated study completion January Estimated study completion March Trial Phase II 17. Sponsor Eisai Limited. Status Abstract. Location Japan. Design Non-randomised, open label. Participants n=299; adults; breast cancer; locally advanced or metastatic; 2-5 prior chemotherapy and (progressed on or within 6 months) with anthracycline, taxane, and capecitabine. schedule Eribulin 1.4mg/m 2 IV on days 1 and 8 of a 21 day cycle. Follow-up 6 months. Primary Overall response rate (ORR); partical response (PR); complete response (CR); duration of outcomes response; progression free survival (PFS) Secondary Safety. outcome Key results Median of 4 cycles (range 1-27). ORR 9.3% (all partial response; 95% CI %) and investigator-assessed ORR 14.1% (1 CR; 95% CI %). Clinical benefit rate (defined as CR + PR + SD>6 months) 17.1% (95% CI %). Median duration of response 3.5 months (range 42±258 days). Median PFS and OS: 2.6 months (1±398 days) and 10.4 months ( days), respectively. Six-month PFS and OS rates: 12.4% and 72.3%. Adverse effects Most frequent (grade 3/4 toxicities): neutropenia (54%; febrile neutropenia: 5.5%), leukopenia (14%), and asthenia/fatigue (10%; no grade 4). Grade 3 peripheral neuropathy in 5.5%. Estimated cost and cost impact The cost of eribulin is not yet known. Potential or intended impact speculative Patients Reduced morbidity Quicker, earlier or more accurate diagnosis or identification of disease Reduced mortality or increased length of survival Other: Improved quality of life for patients and/or carers None identified Services Increased use Service reorganisation required Staff or training required Decreased use Costs Increased unit cost compared to alternative New costs: additional treatment option. Other: if used instead of oral agent, associated IV costs Increased costs: more patients coming for treatment Savings: None identified Increased costs: capital investment needed Other: 4

5 References 1 National Institute for Health and Clinical Excellence. Ixabepilone for locally advanced or metastatic breast cancer. Technology appraisal in development - suspended. London: NICE; April th wave. 2 National Institute for Health and Clinical Excellence. Lapatinib for the treatment of advanced or metastatic breast cancer. Technology appraisal in development. London: NICE; 13 th wave. 3 National Institute for Health and Clinical Excellence. Breast cancer (advanced & metastatic) bevacizumab. Technology appraisal TA147. London: NICE; terminated June National Institute for Health and Clinical Excellence. Breast cancer - gemcitabine for the treatment of metastatic breast cancer. Technology appraisal TA116. London: NICE; January 2007 (review planned for Jan 2010). 5 National Institute for Health and Clinical Excellence. Breast cancer - capecitabine for the treatment of locally advanced or metastatic breast cancer. Technology appraisal TA62. London: NICE; May National Institute for Health and Clinical Excellence. Breast cancer - vinorelbine for the treatment of advanced breast cancer. Technology appraisal TA54. London: NICE; December National Institute for Health and Clinical Excellence. Taxanes for the treatment of breast cancer (review). Technology appraisal TA30. London: NICE; National Institute for Health and Clinical Excellence. Advanced breast cancer diagnosis and treatment. Clinical guideline in development. London: NICE; expected February 2009 (9 th wave). 9 National Institute for Health and Clinical Excellence. Familial breast cancer. Clinical guideline CG41. London: NICE; 2006 (review planned 2010). 10 National Institute for Health and Clinical Excellence. Cancer service guidance - Improving outcomes in breast cancer. London: NICE; August Scottish Intercollegiate Guidelines Network (SIGN). Clinical guideline No. 84: Management of breast cancer in women Cancer Research UK. UK breast cancer incidence statistics. Accessed Cancer Research UK. UK breast cancer mortality statistics. Accessed National Institute for Health and Clinical Excellence. Breast cancer (early) - trastuzumab for the adjuvant treatment of early-stage HER2-positive breast cancer. Technology appraisal TA107. London: NICE; ClinicalTrial.gov. E7389 versus capecitabine in patients with locally recurrent or metastatic breast cancer previously treated with anthracyclines and taxanes. Accessed ClinicalTrial.gov. E7389 versus treatment of physician's choice in patients with locally recurrent or metastatic breast cancer Accessed Vahdat LT, Twelves C, Allison MK et al. Phase II study of eribulin mesylate (E7389) in patients (pts) with locally advanced or metastatic breast cancer (MBC) previously treated with anthracycline, taxane, and capecitabine therapy. Clinical Oncology 26: 2008 (May 20 suppl; abstr 1084 ASCO) The National Institute for Health Research Research Programme is funded by the Department of Health. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health The, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0) Fax +44 (0)