Title: Palbociclib in combination with fulvestrant for treating advanced, hormone-receptor positive, HER2-negative breast cancer after endocrine therapy (review of TA619) [ID3779]
Funder: Department of Health and Social Care

Abstract: Breast cancer arises from the tissues of the ducts or lobules of the breast. The cancer is said to be 'advanced' if it has spread to other parts of the body such as the bones, liver, and lungs (metastatic cancer), or if it has grown directly into nearby tissues and cannot be completely removed by surgery._x000D_ _x000D_ In 2017 in England, around 46,109 people were diagnosed with breast cancer. [1] In 2018 there were 9,640 deaths from breast cancer in England. [2] The 1-year survival rate for adults diagnosed at stage IV (metastatic breast cancer) in England is 66%. [3] Approximately 13% of women with breast cancer have advanced disease when they are diagnosed, [4] and around 35% of people with early or locally advanced disease will progress to metastatic breast cancer in the 10 years following diagnosis. [5] Most (80%) breast cancers are hormone-receptor positive and around two-thirds are oestrogen receptor positive. Human epidermal growth factor receptor 2 (HER2) is present in about 15-25% of breast cancers.[6] Approximately 64% of women with metastatic breast cancer in the UK have hormone-receptor positive, HER2 negative disease. [7]_x000D_ _x000D_ Current treatments for advanced breast cancer aim to relieve symptoms, prolong survival and maintain a good quality of life with few adverse events. Treatment depends on whether the cancer cells have particular receptors (hormone receptor status or human epidermal growth factor receptor 2 [HER2] status), the extent of the disease and previous treatments._x000D_ _x000D_ NICE clinical guideline 81 (CG81) recommends first-line treatment with endocrine therapy for most people with advanced hormone receptor-positive breast cancer. But for people whose disease is life-threatening or requires early relief of symptoms, CG81 recommends chemotherapy. The endocrine therapies used in clinical practice in postmenopausal people include aromatase inhibitors (anastrozole and letrozole) or tamoxifen, if aromatase inhibitors are not tolerated or are contraindicated. Women who are premenopausal or perimenopausal will receive first-line treatment with tamoxifen and ovarian suppression if they have not previously received tamoxifen, while men will receive tamoxifen as a first-line endocrine treatment. NICE technology appraisals 495 and 496 recommend palbociclib with an aromatase inhibitor and ribociclib with and aromatase inhibitor for treating hormone receptor positive, HER2-negative, locally advanced or metastatic breast cancer as initial endocrine based therapy in adults. Fulvestrant is not recommended for untreated locally advanced or metastatic oestrogenreceptor positive breast cancer (NICE technology appraisal 503). _x000D_ _x000D_ For people who receive first-line treatment with anastrozole or letrozole, second-line treatment may be either tamoxifen, exemestane, or everolimus and exemestane (NICE technology appraisal 421). Subsequent treatment options also include chemotherapy for some people. NICE technology appraisals 687 and 725 recommend abemaciclib and ribociclib with fulvestrant for treating hormone receptor-positive, HER2-negative, advanced breast cancer in people who have had previous endocrine therapy (when exemestane plus everolimus is the most appropriate alternative to a CDK 4/6 inhibitor). NICE technology appraisal 619 recommends palbociclib in the same population for use within the Cancer Drugs Fund. This appraisal will update and replace technology appraisal 619. Fulvestrant is not recommended for use following anti-oestrogen therapy, as an alternative to aromatase inhibitors (NICE technology appraisal 239), however, it is sometimes used after exemestane and tamoxifen in people who would otherwise receive chemotherapy._x000D_ _x000D_ References_x000D_ _x000D_ 1. Office for National Statistics (2019) Cancer registration statistics, England, 2017. Accessed January 2020._x000D_ 2. Nomis (2020) Office for National Statistics. Mortality statistics – underlying cause, sex and age: 2018 data. Accessed January 2020._x000D_ 3. Cancer Research UK (2020) Breast cancer incidence statistics: England 2014 data. Accessed January 2020_x000D_ 4. Cancer Research UK (2014) Breast cancer survival statistics. Accessed August 2017._x000D_ 5. Dewis R and Gribbin J (2009) Breast cancer: diagnosis and treatment, an assessment of need. Cardiff: National Collaborating Centre for Cancer. Accessed August 2017._x000D_ 6. NIHR Evidence Briefing. (2017) Alpelisib in combination with fulvestrant for advanced HR positive, HER2-negative breast cancer in men and postmenopausal women. Accessed September 2018._x000D_ 7. NICE. (2017) Resource impact report: Palbociclib with an aromatase inhibitor for previously untreated, hormone receptor positive, HER2-negative, locally advanced or metastatic breast cancer (TA495). Accessed September 2018.

Lay abstract: To appraise the clinical and cost effectiveness of palbociclib within its marketing authorisation for treating advanced hormone receptor-positive, HER2-negative breast cancer.

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