NIHRDataInsights/HRCSData huggingface dataset:
Title: Pembrolizumab for adjuvant treatment of resected melanoma with high risk of recurrence [ID1266]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of pembrolizumab within its marketing authorisation for adjuvant treatment of resected melanoma with high risk of recurrence

Lay abstract: Cutaneous melanoma is a cancer of the skin. In its early stages, melanoma is normally asymptomatic and can often be cured by surgery (resection). However, it can spread or metastasise to nearby lymph nodes or to other parts of the body. Most melanomas occur in people with pale skin. The risk factors are skin that tends to burn in the sun, having many moles, intermittent sun exposure and sunburn. There were 12,993 new diagnoses of melanoma in 2014 and 2,080 deaths registered in England (1). In the UK in 2012-2014, on average half of cases were diagnosed in people aged 65 and over (1). The stage of melanoma describes how deeply it has grown into the skin, and whether it has spread. At stage I and II, there is no evidence that the tumour has spread anywhere else in the body, although there is a possibility of microscopic spread. Stage III melanoma means that the melanoma cells have spread into skin, lymph vessels, or lymph glands close to the melanoma. Stage III melanomas are considered intermediate to high risk as they more likely to spread to other distant parts of the body (stage IV melanoma) than in earlier melanoma stages. In 2012, the proportion of people in the UK diagnosed with melanoma at stage III disease was 3% (2). Five-year survival rates are approximately 50-55% for stage III disease (3). Advanced melanoma (stage IV) means the cancer has spread from where it started to another part of the body. Surgery (tumour removal and wide local excision) is the main treatment for early (stage I) and medium stage (stage II and III) melanoma. Surgical removal of the nearby lymph nodes is also considered if there is evidence of microscopic spread. Early recognition of melanoma and accurate diagnosis present the best opportunities for cure. Adjuvant chemotherapy and immunotherapy following tumour removal are not widely used in UK practice. References: 1. Cancer Research UK (2014) Skin cancer statistics. Accessed September 2017 http://www.cancerresearchuk.org/health-professional/cancer- statistics/statistics-by-cancer-type/skin-cancer 2. National Cancer Intelligence Network and Cancer Research UK (2015) Routes to diagnosis by stage 2012-2013 workbook. Accessed September 2017 http://www.ncin.org.uk/publications/routes_to_diagnosis 3. Cancer Research UK (2014) Skin cancer survival statistics. Accessed September 2017 http://www.cancerresearchuk.org/health-professional/cancer- statistics/statistics-by-cancer-type/skin-cancer/survival#heading-Three

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Dabrafenib and trametinib for treating adjuvant therapy for melanoma after surgical resection [ID1226]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of dabrafenib in combination with trametinib within their marketing authorisations for adjunctive treatment of resected BRAF V600 mutation-positive malignant melanoma.

Lay abstract: Cutaneous melanoma is a cancer of the skin. In its early stages, melanoma is normally asymptomatic and can often be cured by surgery (resection). However, it can spread or metastasise to nearby lymph nodes (stage III) or to other parts of the body (stage IV). Most melanomas occur in people with pale skin. The risk factors are skin that tends to burn in the sun, having many moles, intermittent sun exposure and sunburn. There were 12,993 new diagnoses of melanoma in 2014 and 2,080 deaths registered in the England.(1) In the UK in 2012-2014, on average half of cases were diagnosed in people aged 65 and over.(1) A mutated form of the BRAF gene is found in about 50% of melanomas; over 90% of these are BRAF V600 mutations.(2) Mutated BRAF genes activate the RAF-MEK-ERK pathway, leading to uncontrolled cell division and growth of the tumour. The stage of melanoma describes how deeply it has grown into the skin, and whether it has spread. At stage I and II, there is no evidence that the tumour has spread anywhere else in the body, although there is a possibility of microscopic spread. Stage III melanoma means that the melanoma cells have spread into skin, lymph vessels, or lymph glands close to the melanoma. Stage III melanomas are considered intermediate to high risk as they more likely to spread to other distant parts of the body (stage IV melanoma) than in earlier melanoma stages. In 2012, the proportion of people in the UK diagnosed with melanoma at stage III disease was 3%.(2) Five-year survival rates are approximately 50-55% for stage III disease.(3) Advanced melanoma (stage IV) means the cancer has spread from where it started to another part of the body. Surgery (tumour removal and wide local excision) is the main treatment for early (stage I) and medium stage (stage II and III) melanoma. Surgical removal of the nearly lymph nodes is also considered if there is evidence of microscopic spread. Early recognition of melanoma and accurate diagnosis present the best opportunities for cure. Adjuvant chemotherapy and immunotherapy following tumour removal are not widely used in UK practice. References 1. Cancer Research UK (2014) Skin cancer statistics. Accessed August 2017 2. Ascierto PA, Kirkwood JM, Grob J-J, et al. (2012) The role of BRAF V600 mutation in melanoma. Journal of Translational Medicine 10:85. 3. National Cancer Intelligence Network and Cancer Research UK (2015) Routes to diagnosis by stage 2012-2013 workbook. Accessed August 2017 4. Cancer Research UK (2014) Skin cancer survival statistics. Accessed August 2017

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Abemaciclib with an aromatase inhibitor for untreated advanced hormone-receptor positive, HER2-negative breast cancer [ID1227]
Funder: Department of Health and Social Care

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

Lay 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. In 2015 in England, around 46,083 people were diagnosed with breast cancer (1). In 2016 there were 9,685 deaths from breast cancer in England (2). The 1-year survival rate for adults with metastatic breast cancer in England is 63% (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). Current treatments for advanced breast cancer aim to relieve symptoms, prolong survival and maintain a good quality of life with minimal adverse events. Treatment may depend on whether the cancer cells have particular receptors (hormone receptor status or HER2 status), the extent of the disease, and previous treatments. 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 for advanced hormone receptor-positive breast cancer in postmenopausal people include aromatase inhibitors (anastrozole and letrozole) and tamoxifen, only if aromatase inhibitors are not tolerated or are contraindicated. People who are premenopausal or perimenopausal will receive first-line treatment with tamoxifen and ovarian suppression if they have not previously received tamoxifen. 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. References 1 Office for National Statistics (2017) Cancer registration statistics, England, 2015. Accessed August 2017. 2 Office for National Statistics (2017) Mortality statistics – underlying cause, sex and age. Accessed December 2017. 3 Cancer Research UK (2014) Breast cancer survival statistics. Accessed August 2017. 4 Cancer Research UK (2014) Breast cancer incidence statistics. Accessed August 2017. 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.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Osimertinib for untreated epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer [ID1302]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of osimertinib within its marketing authorisation for treating epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer that has not previously been treated.

Lay abstract: Lung cancer falls into two main histological categories: around 85–90% are non-small-cell lung cancers (NSCLC) and the remainder are small-cell lung cancers. NSCLC can be further classified into 3 histological sub-types of large-cell undifferentiated carcinoma, squamous cell carcinoma and adenocarcinoma. The majority of lung cancers are diagnosed at an advanced stage, when the cancer has spread to lymph nodes and other organs in the chest (locally advanced disease; stage III) or to other parts of the body (metastatic disease; stage IV). In 2015, around 33,000 people were estimated to be diagnosed with NSCLC in England.(1),(2) Around 12% have stage IIIA, 9% had stage IIIB and 53% had stage IV disease1. The prognosis for people with non-small-cell lung cancer is generally poor. Between 2011 and 2015 around 39% of people with lung cancer survived for 1 year or longer and only 15% survived for 5 years or longer.(2) For the majority of people with NSCLC, the aims of therapy are to prolong survival and improve quality of life. Treatment choices may be influenced by the presence of biological markers (such as the checkpoint inhibitor programmed death-ligand 1 [PD-L1] and mutations in epidermal growth factor receptor-tyrosine kinase [EGFR-TK] or anaplastic-lymphoma-kinase [ALK], or), histology (squamous or non-squamous) and previous treatment experience. For people whose locally advanced or metastatic disease tests positive for the activating EGFR-TK mutation and who have not previously had treatment, NICE guidance recommends the tyrosine kinase inhibitors (TKI) afatinib, erlotinib and gefitinib as treatment options (NICE technology appraisal guidance 310, 258 and 192 respectively). References 1 National lung cancer audit 2016 (2017). Royal college of Physicians. Accessed October 2017. 2 Cancer survival in England: adult, stage at diagnosis and childhood-patients followed up to 2016 (2017) Office for National Statistics. Accessed October 2017

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Tisagenlecleucel-T for treating relapsed or refractory diffuse large B-cell lymphoma [ID1166]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of tisagenlecleucel-T within its marketing authorisation for treating relapsed or refractory diffuse large B-cell lymphoma.

Lay abstract: Lymphomas are cancers of the lymphatic system, which is a part of the immune system. Lymphomas are divided into Hodgkin lymphoma and non- Hodgkin lymphoma. Non-Hodgkin lymphomas (NHL) are a diverse group of conditions which are categorised according to the cell type affected (B-cell or T-cell), as well as the clinical features and rate of progression of the disease. The most common B-cell lymphomas are follicular lymphoma (FL) which is a slow growing, low grade form of NHL and diffuse large B-cell lymphomas (DLBCL), a fast growing, high grade form of NHL. Some FLs transform into high grade DLBCL (transformed high grade FL). The symptoms differ depending on which organ or tissues are affected by the lymphoma. NHL often presents as painless lumps (enlarged lymph nodes) in the neck, armpit or groin but sometimes may start in other parts of the body such as the stomach or bowel (extranodal disease). People may also have loss of appetite, tiredness or night sweats. There were around 11,690 new cases of non-Hodgkin lymphoma (NHL) in England in 2015 with 4,688 of these being for DLBCL.(1) Most people diagnosed with DLBCL are 65 or over.(2) Survival rates at 5 years for DLBCL are around 65-70% for stage I and II and around 50% at stages III and IV.(2),(3) The most widely used first-line treatment for DLBCL is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone). Sometimes etoposide is added to this regimen. NICE guideline NG52 recommends chemotherapy in combination with rituximab for relapsed or refractory disease followed by stem cell transplantation. Chemotherapy regimens commonly used in clinical practice include DHAP (dexamethasone, cytarabine, cisplatin), GDP (gemcitabine, dexamethasone, cisplatin), ICE (ifosfamide, carboplatin, etoposide) and IVE (ifosfamide, etoposide, epirubicin). If stem cell transplantation is not suitable, further chemotherapy or immunotherapy may be used alone. NICE technology appraisal 306 recommends pixantrone monotherapy for people who have multiply relapsed or refractory aggressive non-Hodgkin B-cell lymphoma, when they have been treated previously with rituximab and are in the third or fourth line of treatment. References 1. Office of National Statistics (2017) Cancer Registration Statistics: England 2015 [accessed November 2017]. 2. Diffuse B-cell lymphoma. Lymphoma association [accessed March 2018]. 3. Cancer Research UK (2015) Survival for high grade lymphomas [accessed November 2017].

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Nivolumab with ipilimumab for first line, advanced or metastatic renal cell carcinoma [ID1182]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of nivolumab in combination with ipilimumab within its marketing authorisation for untreated, intermediate or poor risk, advanced or metastatic renal cell carcinoma.

Lay abstract: Renal cell carcinoma (RCC) is a cancer that usually originates in the lining of the tubules of the kidney (the smallest tubes inside the nephrons) that help filter the blood and make urine. RCC is the most common type of kidney cancer (more than 80% of the cases)(1). There are several types of RCC. The main ones are clear cell (accounting for approximately 75% of cases),1 papillary and chromophobe. RCC is graded into stages I to IV. Stage III denotes disease that is locally advanced and/or has spread to regional lymph nodes. Metastatic RCC, in which the tumour has spread beyond the regional lymph nodes to other parts of the body, is defined as stage IV. Early small RCC tumours are usually asymptomatic; the diagnosis of early RCC is often incidental after abdominal scans for other reasons. The most common presenting symptoms of advanced RCC are blood in the urine (haematuria), a palpable mass in the flank or abdomen and abdominal pain. Other non-specific symptoms include fever, night sweats, malaise and weight loss. Localised radical approaches including nephron-sparing surgery, radical nephrectomy and ablative therapies may be curative in people with localised tumours. However, around half of those who have surgery develop advanced disease later on. In 2015, 10,507 new kidney cancers were diagnosed in England.(2) In 2014, approximately 44% of people diagnosed with kidney cancer had stage III or IV disease and 25% to 31% had metastases.(3) The 5-year relative survival rate for stage IV RCC is approximately 6%.(4) The aim of treatment is to prevent the growth and survival of cancer cells within the tumour. In untreated RCC, NICE technology appraisal guidance 169 recommends sunitinib as a ‘first-line treatment option for people with advanced and/or metastatic renal cell carcinoma who are suitable for immunotherapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.’ NICE technology appraisal guidance 215 recommends pazopanib as a ‘first-line treatment option for people with advanced renal cell carcinoma who have not received prior cytokine therapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1’. References 1. Cancer Research UK (2016) Types of kidney cancer. Accessed July 2017. 2. Office for National Statistics (2017) Cancer Registration Statistics. Accessed July 2017. 3. Cancer Research UK (2017) Kidney cancer incidence statistics. Accessed July 2017. 4. Cancer Research UK (2016) Kidney cancer survival statistics. Accessed July 2017.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Pembrolizumab for first line treatment of locally advanced or metastatic non-small cell lung cancer [ID1173]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of pembrolizumab in combination with pemetrexed and platinum chemotherapy within its marketing authorisation for untreated, metastatic, non-squamous non-small-cell lung cancer.

Lay abstract: Lung cancer falls into two main histological categories: around 85–90% are non-small-cell lung cancers (NSCLC) and the remainder are small-cell lung cancers (1),(2). NSCLC can be further classified into 3 histological sub-types of large-cell undifferentiated carcinoma, squamous cell carcinoma and adenocarcinoma. Most lung cancers are diagnosed at an advanced stage, when the cancer has spread to lymph nodes and other organs in the chest (locally advanced disease; stage III) or to other parts of the body (metastatic disease; stage IV). In 2015, approximately 31,700 people were diagnosed with NSCLC in England, of whom 53% had stage IV disease (2). Around a third of people with lung cancer survive for more than 1 year after diagnosis (2), however this is reduced to a fifth of people diagnosed at stage IV (3). For the majority of people with NSCLC, the aims of treatment are to prolong survival and improve quality of life. Treatment choices are influenced by the presence of biological markers (such as mutations in epidermal growth factor receptor-tyrosine kinase [EGFR-TK], anaplastic-lymphoma-kinase [ALK] or PD-L1 status), histology (squamous or non-squamous) and previous treatment experience. NICE clinical guideline 121 recommends platinum combination chemotherapy (that is, cisplatin or carboplatin, and either docetaxel, gemcitabine, paclitaxel, or vinorelbine) as an option for people with previously untreated stage III or IV NSCLC and good performance status. Alternatively, people may receive pemetrexed in combination with cisplatin if the histology of the tumour has been confirmed as adenocarcinoma or large- cell carcinoma (NICE technology appraisal guidance 181). For non-squamous NSCLC that has not progressed immediately following initial therapy with a NICE-recommended platinum-based chemotherapy regimen, maintenance treatment with pemetrexed is recommended as an option (NICE technology appraisal guidance 190 and 402). Pembrolizumab monotherapy is currently recommended for use within the Cancer Drugs Fund as an option for people whose tumours express PD-L1 with at least a 50% tumour proportion score and have no EGFR- or ALK-positive mutations (NICE technology appraisal guidance 447). Best supportive care may be considered for some people for whom chemotherapy is unsuitable or may not be tolerated. References 1 Cancer Research UK (2017) Lung cancer incidence statistics (2011 data). Accessed March 2018. 2 Royal College of Physicians (2017) National Lung Cancer Audit annual report 2016 (for the audit period 2015). Accessed March 2018. 3 Cancer Research UK (2017) Lung cancer survival statistics (2014 data). Accessed March 2018.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Pembrolizumab for locally advanced or metastatic urothelial cancer where cisplatin is unsuitable [ID1209]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of pembrolizumab within its marketing authorisation for treating locally advanced or metastatic urothelial carcinoma in people for whom cisplatin-based chemotherapy is unsuitable.

Lay abstract: Urothelial carcinoma is cancer of the transitional cells that form the inner lining of the bladder, urethra, ureter, or renal pelvis. Urothelial carcinoma is most common in the bladder, and accounts for approximately 90% of bladder cancers.(1) Urothelial carcinomas can be described as non-invasive or invasive depending on how far the carcinomas invade the tissues. Non-invasive urothelial carcinomas can be further split into papillary carcinomas or flat carcinomas. Papillary carcinomas often grow towards the hollow part of the organ (for example bladder and ureter), without going into deeper layers. Flat carcinomas remain in the inner layers. Both papillary and flat carcinomas can become invasive. In 2015, 8,500 new bladder cancers were diagnosed in England.(2) Bladder cancer accounts for around 1 in every 30 new cancer diagnoses each year in the UK, with an overall incidence of around 17 per 100,000.(3) The majority of cases are in those over the age of 60 but can also affect young people too, and is more common in men than women (around 3:1).3 Smoking is a major factor in the cause of bladder cancer. People with locally advanced or metastatic urothelial carcinoma may receive treatment with surgery and/or radiotherapy. Chemotherapy may be given before (neoadjuvant) or after surgery and/or radiotherapy in an attempt to improve cure rates. If the cancer is too advanced for surgery/radiotherapy or has recurred after these treatments, first-line chemotherapy can be used to improve quality of life and survival. NICE guideline NG2 recommends carboplatin plus gemcitabine for people with locally advanced or metastatic urothelial bladder cancer for whom cisplatin-based chemotherapy regimen is unsuitable. Best supportive care may also be offered to people with locally nced or metastatic urothelial bladder cancer. References 1. Cancer Research UK (2015) Types of bladder cancer. Accessed September 2017. 2. Office for National Statistics (2017) Cancer Registration Statistics, England: 2015. Accessed September 2017. 3. Cancer Research UK (2016) Bladder cancer incidence statistics. Accessed September 2017.

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