Title: Pembrolizumab in combination for untreated, locally recurrent inoperable or metastatic, triple negative breast cancer [ID1546]
Funder: Department of Health and Social Care

Abstract: Breast cancer arises from the tissues of the ducts or lobules of the breast. Locally recurrent cancer is cancer that has come back after an initial treatment, at or near the same place as the original tumour. Inoperable cancer is cancer that cannot be completely removed by surgery. Metastatic cancer is cancer that has spread to other parts of the body such as the bones, liver, and lungs._x000D_ _x000D_ In 2017, there were over 46,100 people diagnosed with breast cancer in England, and there were approximately 9,502 deaths from breast cancer.[1],[2] The 5-year survival rate for people with metastatic breast cancer in England is 15%.[3] Approximately 16% of people with invasive breast cancers have locally advanced or metastatic disease when they are diagnosed,[4] and around 35% of people with early or locally advanced disease will progress to metastatic breast cancer.[5]_x000D_ _x000D_ Around 15% of breast cancers (approximately 7500 cases a year in England and Wales) are triple negative breast cancers whereby the cancer cells test negative for oestrogen and progesterone receptors (hormone receptor negative cancer) and human epidermal growth factor receptor 2 (HER2-negative cancer). It is diagnosed more frequently in younger people and people with BRCA1 mutations (a gene on chromosome 17 that normally helps to suppress cell growth, which is an inherited gene mutation that may increase the risk of breast cancer). Triple negative breast cancer can be particularly aggressive, is more likely to recur than other breast cancers, and is associated with poorer survival.[6]_x000D_ _x000D_ Chemotherapy is the main treatment for advanced triple negative breast cancer. CG81 recommends single-agent docetaxel as a first-line treatment for advanced breast cancer not suitable for anthracyclines (because it is contraindicated or because of prior anthracycline treatment). It considers combination chemotherapy for people for whom a greater probability of response is important and who understand and are likely to tolerate the additional toxicity. TA639 recommends atezolizumab with nab-paclitaxel for treating triple-negative, unresectable, locally advanced or metastatic breast cancer in adults whose tumours express PD-L1 at a level of 1% or more and who have not had previous chemotherapy for metastatic disease._x000D_ _x000D_ References_x000D_ _x000D_ 1 Office for National Statistics (2019) Cancer registration statistics, England, 2017. Accessed April 2020._x000D_ _x000D_ 2 Cancer research UK (2019) Breast cancer mortality statistics. Accessed April 2020._x000D_ _x000D_ 3 Cancer Research UK (2014) Breast cancer survival statistics. Accessed October 2018._x000D_ _x000D_ 4 Cancer Research UK (2014) Breast cancer incidence statistics. Accessed October 2018._x000D_ _x000D_ 5 Dewis R and Gribbin J (2009) Breast cancer: diagnosis and treatment, an assessment of need. Cardiff: National Collaborating Centre for Cancer. Accessed October 2018._x000D_ _x000D_ 6 Couch FJ, Hart SN, Sharma P et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. Journal of Clinical Oncology 2015;33(4):304-311.

Lay abstract: To appraise the clinical and cost effectiveness of pembrolizumab within its marketing authorisation for treating untreated, locally recurrent inoperable or metastatic, triple negative breast cancer.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS