NIHRDataInsights/HRCSData huggingface dataset:
Title: Dabrafenib and trametinib for advanced non-small cell lung cancer with a BRAF V600 mutation [ID3851]
Funder: Department of Health and Social Care

Abstract: Lung cancer falls into 2 main histological categories: around 80–85% are non-smallcell lung cancers (NSCLC) and the remainder are small cell lung cancers.[1] NSCLC can be further classified into 3 main histological sub-types of large-cell undifferentiated carcinoma, squamous cell carcinoma and adenocarcinoma.[1] 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 3) or to other parts of the body (metastatic disease; stage 4). BRAF is a protein which is part of the mitogen activated protein kinase signalling pathway, which helps to regulate cell proliferation, differentiation and death.[2]_x000D_ _x000D_ In 2020 around 28,300 cases of non-small-cell lung cancer were diagnosed in England.[3] In the same year 19% of all lung cancer cases were stage 3 and 40% were stage 4.[3] Lung cancer survival rates are relatively low, between 2013 and 2017 40% of people with lung cancer survived for one year and 16% survived for 5 years or longer. BRAF mutations are found in approximately 1-4% of NSCLCs, and of these mutations about 50% are BRAF V600E mutations.[4]_x000D_ _x000D_ Current clinical management for advanced or metastatic (stage 3 or 4) NSCLC typically aims to control the cancer for as long as possible and help with symptoms. Treatment generally includes surgery, chemotherapy, radiotherapy, chemoradiation or targeted small molecule and immunotherapy drugs. Treatment choices are influenced by the histology of the condition (squamous, or non-squamous) and by previous treatments. Choices are also influenced by the presence of certain biomarkers such as the programmed cell death-ligand 1 (PD-L1) or mutations affecting proteins such as epidermal growth factor receptor (EGFR), anaplasticlymphoma kinase (ALK) or the ROS-1 and KRAS receptors. There are specific NICE treatment pathways for cancers which have EGFR, ALK, ROS-1 or KRAS gene mutations but not currently for BRAF mutations._x000D_ _x000D_ References_x000D_ 1. Cancer Research UK (2020) Types of lung cancer. Accessed April 2022_x000D_ 2. Chan, X. Y. et al (2017) Role Played by Signalling Pathways in Overcoming BRAF Inhibitor Resistance in Melanoma_x000D_ 3. National Lung Cancer Audit (2022) Annual Report (2019/2020 data) Accessed April 2022_x000D_ 4. Shiau, C.J. Tsao, M. -S. (2017). Diagnostic Molecular Pathology. Chapter 23: Molecular testing in lung cancer Accessed April 2022

Lay abstract: To appraise the clinical and cost effectiveness of dabrafenib in combination with trametinib within its marketing authorisation for treating advanced, metastatic BRAF V600 mutation-positive non-small-cell lung cancer.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Daratumumab with lenalidomide and dexamethasone for untreated multiple myeloma when stem cell transplant is unsuitable [ID4014]
Funder: Department of Health and Social Care

Abstract: Multiple myeloma is a form of cancer that arises from plasma cells (a type of white blood cell) in the bone marrow. Myeloma cells suppress the development of normal blood cells that are responsible for fighting infection (white blood cells), carrying oxygen around the body (red blood cells) and blood clotting (platelets). The term multiple myeloma refers to the presence of more than one site of affected bone at the time of diagnosis. People with multiple myeloma can experience bone pain, bone fractures, tiredness (as a result of anaemia), infections, hypercalcaemia (too much calcium in the blood) and kidney problems. _x000D_ _x000D_ There were 5,041 newly diagnosed cases of multiple myeloma in England in 2019.[1] Fifty-nine percent of people diagnosed in the UK are aged 70 years and over. Multiple myeloma is more common in men than in women and the incidence is also reported to be higher in people of African family origin.[2] The 5-year survival rate for adults with multiple myeloma in England and Wales is about 52%.[3]_x000D_ _x000D_ Multiple myeloma is an incurable disease. Therapy aims to prolong survival and maintain a good quality of life by controlling the disease and relieving symptoms. High-dose chemotherapy with autologous stem-cell transplantation may be an option for people with multiple myeloma in good general health; however, this is an intensive treatment, which is not considered appropriate for most people with multiple myeloma._x000D_ _x000D_ NICE technology appraisal guidance 228 recommends thalidomide in combination with an alkylating agent and a corticosteroid for the first-line treatment of multiple myeloma in people for whom high-dose chemotherapy when stem cell transplantation is considered inappropriate. If the person is unable to tolerate or has contraindications to thalidomide, treatment options include bortezomib in combination with an alkylating agent and a corticosteroid (NICE technology appraisal guidance 228), and lenalidomide plus dexamethasone (NICE technology appraisal guidance 587)._x000D_ _x000D_ References_x000D_ 1. Cancer Research UK, Myeloma incidence statistics. Accessed February 2022._x000D_ 2. Cancer Research UK ‘Myeloma incidence’. Accessed February 2022._x000D_ 3. Cancer Research UK ‘Myeloma survival’. Accessed February 2022.

Lay abstract: To appraise the clinical and cost effectiveness of daratumumab with lenalidomide and dexamethasone within its marketing authorisation for untreated multiple myeloma when stem cell transplant is unsuitable.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Tebentafusp for the treatment of advanced (metastatic or unresectable) uveal melanoma in HLA-A*02:01 positive adults [ID1441]
Funder: Department of Health and Social Care

Abstract: Uveal melanoma is a rare type of cancer, arising from blood-rich structures in the middle of the eye (iris, choroid or ciliary body). Uveal melanoma is biologically distinct from skin melanoma with different physiological, genetic, and epidemiologic characteristics. It is often discovered through routine optometrist eye examination. Depending on tumour location, it may not cause any symptoms until it is quite large. Symptoms include flashes of light, blurry vision, loss of vision, or floaters (spots, lines or rings moving through field of vision).1_x000D_ _x000D_ Uveal melanoma has 2 distinct disease states. Stages 1 to 3 are when the tumour is contained to the eye (primary disease), and stage 4 is when it has spread to distant organs (metastatic). 1 The cancer cells often spread to the liver, but can also spread to the lungs and bones.2_x000D_ _x000D_ In England in 2017 there were 481 registrations of newly diagnosed cancer of the choroid (ICD-10 code C69.3) and 59 registrations of cancer of the ciliary body (ICD10 code C69.4).3 The total number of newly diagnosed cancers of the eye and adnexa (surrounding tissue, ICD-10 code C69) was 701. The total number of deaths recorded under the same ICD-10 code was 119.3 Around 47% of uveal melanoma is human leukocyte antigen (HLA)-A*0201 positive.4 Outcomes are poor once metastatic disease occurs. The median survival from development of metastatic disease is around 13 months, 5 and 1-year survival is around 50%.6_x000D_ _x000D_ People with advanced (unresectable or metastatic) uveal melanoma are usually offered immunotherapy, although the evidence for these is based on cutaneous melanoma. NICE has recommended the following immunotherapies for use in melanoma: ipilimumab (NICE technology appraisal guidance 268 and NICE technology appraisal guidance 319), pembrolizumab (NICE technology appraisal guidance 357 and NICE technology appraisal guidance 366) and nivolumab alone (NICE technology appraisal guidance 384) or with ipilimumab (NICE technology appraisal guidance 400). People for whom immunotherapy is not suitable may have dacarbazine chemotherapy or best supportive care.

Lay abstract: To appraise the clinical and cost effectiveness of tebentafusp within its marketing authorisation for treating advanced (unresectable or metastatic) HLA-A*0201-positive uveal melanoma.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Abemaciclib in combination with endocrine therapy for adjuvant treatment of hormone receptor-positive, HER2-negative, node-positive early breast cancer [ID3857]
Funder: Department of Health and Social Care

Abstract: Breast cancer arises from the tissues of the ducts or lobules of the breast. Breast cancer is described as ‘early’ if it is restricted to the breast or the breast and near lymph nodes, and has not spread to other parts of the body._x000D_ _x000D_ In 2017, there were approximately 46,109 new diagnoses of breast cancer in England. [1] In 2017 in England, there were 10,219 deaths from breast cancer.[2] There were approximately 36,508 cases of early breast cancer in the UK in 2017 according to the National Cancer Registration and Analysis Service.[3] Most (80%) breast cancers are hormone receptor-positive and around two-thirds are oestrogen receptor positive. [4] Between 80-85% of women with breast cancer will have HER2-negative tumours. [5]_x000D_ _x000D_ 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._x000D_ _x000D_ Adjuvant therapy is used to reduce the risk of the cancer coming back after surgery. The decision about whether to have adjuvant therapy is based on the assessment of the risk of the cancer coming back and the potential benefits and side effects of the treatment. NICE guideline 101 recommends adjuvant endocrine therapy (tamoxifen or aromatase inhibitors such as anastrozole and letrozole) for hormone receptorpositive early breast cancer. It also recommends considering ovarian function suppression for premenopausal women and extended endocrine therapy (total duration of endocrine therapy of more than 5 years). Adjuvant chemotherapy (a regimen containing both a taxane and an anthracycline), adjuvant radiotherapy and adjuvant bisphosphonate therapy (for post-menopausal women) are also recommended for early breast cancer._x000D_ _x000D_ References_x000D_ 1. Office for National Statistics (2019) Cancer registration statistics, England, 2017. Accessed January 2021._x000D_ 2. Office for National Statistics. Death Registrations Summary Statistics, England and Wales, 2017. Accessed January 2021._x000D_ 3. National Cancer Registration and Analysis Service (NCRAS). Stage breakdown by CCG 2017. London: Public Health England, 2017. Accessed January 2021._x000D_ 4. Dewis R and Gribbin J (2009) Breast cancer: diagnosis and treatment, an assessment of need. Cardiff: National Collaborating Centre for Cancer. Accessed January 2021._x000D_ 5. Macmillan Cancer Support Receptors for HER2 Accessed January 2021.

Lay abstract: To appraise the clinical and cost effectiveness of abemaciclib in combination with endocrine therapy within its marketing authorisation for adjuvant treatment of hormone receptor-positive, HER2-negative, node-positive early breast cancer at high-risk of recurrence.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Pembrolizumab for adjuvant treatment of renal cell carcinoma [ID3810]
Funder: Department of Health and Social Care

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). 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 I and II includes tumours which are localised to the kidney. 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._x000D_ _x000D_ In 2017, 10,759 new kidney cancer cases were diagnosed in England. The incidence rate of kidney cancer increases with age and is highest in people over 85 years of age[1] ._x000D_ _x000D_ Treatment options for localised tumours include laproscopic or open surgery (nephrectomy), which can be partial (nephron sparing) or total, and ablation techniques including radiofrequency ablation and cryoablation . These are performed with curative intent. NICE cancer service guideline 2, ‘Improving outcomes in urological cancer’ recommends that surgery can also be considered when there is metastatic disease. After surgery, the disease may relapse and spread to other parts of the body. The aim of adjuvant treatment is to reduce the number of people whose disease relapses. NICE has not appraised a treatment to reduce the risk of recurrence after surgery for renal cell carcinoma before._x000D_ _x000D_ References_x000D_ 1 Cancer Research UK Kidney cancer types and grades. Accessed October 2020_x000D_ 2 Cancer Research UK Kidney cancer incidence statistics. Accessed October 2020.

Lay abstract: To appraise the clinical and cost effectiveness of pembrolizumab within its marketing authorisation for adjuvant treatment of renal cell carcinoma after nephrectomy.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Cabozantinib for previously treated advanced hepatocellular carcinoma (review of TA582) [ID3917]
Funder: Department of Health and Social Care

Abstract: Hepatocellular carcinoma (HCC) is the most common form of liver cancer in England, accounting for 55% of primary liver cancer diagnoses in men and 28% of diagnoses in women[1] . There were 4,975 people diagnosed with liver cancer in England in 2017 [2] . HCC is commonly associated with cirrhosis (scarring of the liver), which can develop following long periods of chronic liver disease._x000D_ _x000D_ Treatment for HCC depends on the location and stage of the cancer, and how well the liver function is preserved._x000D_ _x000D_ For people with advanced disease and those whose disease has progressed while on locoregional therapy or for whom locoregional therapy is not suitable, first-line systemic treatment options include sorafenib (NICE technology appraisal guidance 474), lenvatinib (NICE technology appraisal guidance 551) and atezolizumab plus bevacizumab (NICE technology appraisal guidance 666). For people with disease progression on atezolizumab plus bevacizumab, sorafenib may be given as second-line treatment. For people with disease progression on sorafenib, NICE technology appraisal 555 recommends regorafenib. For some people, regorafenib may not be suitable because sorafenib was poorly tolerated and they may have best supportive care instead._x000D_ _x000D_ References_x000D_ 1. National Cancer Registration and Analysis Service (2010) Trends in incidences in primary liver cancer subtypes. Accessed April 20212._x000D_ 2. Office for National Statistics Cancer registration statistics, England: 2017 (April 2019)

Lay abstract: To appraise the clinical and cost effectiveness of cabozantinib within its marketing authorisation for previously treated advanced hepatocellular carcinoma.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Pembrolizumab with lenvatinib for previously treated advanced, metastatic or recurrent endometrial cancer [ID3811]
Funder: Department of Health and Social Care

Abstract: Endometrial cancer is a cancer of the lining of the womb (uterus), known as the endometrium. It is the most common type of womb cancer and often diagnosed in the earlier stages. When diagnosed, endometrial cancer is categorised between stage 1 and 4. Advanced endometrial cancer is defined as stage 3 or 4, where the cancer has spread outside the womb. In stage 3 the spread of cancer is contained within the pelvis, once the cancer has spread into another area of the body it is classed as stage 4 or metastatic (stages 3 and 4 are known are advanced cancer). Recurrent endometrial cancer is when the cancer returns after primary treatment. The cancer can recur anywhere, common areas include the abdominal cavity, lymph nodes, lung and vagina. The symptoms of recurrence are variable but include abdominal pain, bloating, nausea, shortness of breath, vaginal bleeding and changes in bowel or bladder habits[1] ._x000D_ _x000D_ There are approximately 9,400 new cases of endometrial cancer every year in the UK. Around 2,400 deaths occurred in 2018 which accounts for 3% of all cancer deaths in females in the UK. Only 15% of women diagnosed with advanced or recurrent endometrial cancer at late stage survive for more than 5 years, compared to 92% of women diagnosed at early stage[2] . Less than 5% of endometrial cancers occur in women under 45 years of age[3] ._x000D_ _x000D_ The first treatment for endometrial cancer is usually removal of the womb (hysterectomy) as well as both fallopian tubes and ovaries (bilateral salpingooophorectomy). In advanced endometrial cancer, debulking surgery may be carried out to remove as much of the cancer as possible[4] . Radiotherapy may be used for people who cannot have surgery, or alongside surgical treatment. Platinum-based chemotherapy can be used as an adjunct to surgery for people with stage 2 to 4 disease. Hormone therapy with progestins, or platinum-based chemotherapy may be used for cancer that has metastasised or relapsed. _x000D_ _x000D_ References_x000D_ 1 Murali R, Soslow RA, Weigelt B (2014) Classification of endometrial carcinoma: more than two types. The Lancet. Oncology 15(7): 268-278._x000D_ 2 Cancer Research UK (2017) Uterine cancer statistics. Accessed September 2020._x000D_ 3 British Gynaecological Cancer Society (2017) BGCS uterine cancer guidelines: recommendations for practice. Accessed September 2020._x000D_ 4 NHS (2018) Treatment: Womb (uterus) cancer. Accessed September 2020.

Lay abstract: To appraise the clinical and cost effectiveness of pembrolizumab with lenvatinib within its marketing authorisation for treating previously treated advanced, metastatic or recurrent endometrial cancer.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Aumolertinib for untreated EGFR mutation-positive non-small-cell lung cancer [ID4000]
Funder: Department of Health and Social Care

Abstract: Lung cancer falls into 2 main histological categories: around 88% are non-small-cell lung cancers (NSCLC) and the remainder are small cell lung cancers.[1] NSCLC can be further classified into squamous cell carcinoma and non-squamous cell carcinoma. Around 85% of NSCLC cases are of non-squamous histology and can be either large-cell undifferentiated carcinoma or adenocarcinoma.[2] 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 3) or to other parts of the body (metastatic disease; stage 4). People with NSCLC can have either EGFRpositive or EGFR-negative lung cancer. NSCLC with EGFR activating mutations is considered to be a genetically distinct form of lung cancer which is most common in people with adenocarcinoma, non-smokers, people of Asian origin and females. Overexpression of EGFR has been detected in 10-15% of NSCLC. _x000D_ _x000D_ In 2018, 21,878 people were diagnosed with NSCLC in England, and around 68% had stage 3 or 4 disease. [3] Around a third of people with lung cancer survive for more than 1 year after diagnosis, however this is reduced to around a fifth of people diagnosed at stage 4. [4]_x000D_ _x000D_ For most 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 (PDL1), mutations in EGFR, anaplastic-lymphoma-kinase (ALK), receptor tyrosine kinase (ROS1) or KRAS, histology (squamous or non-squamous), and previous treatment experience._x000D_ _x000D_ For people whose locally advanced or metastatic disease tests positive for the EGFR mutation and who have not previously had treatment, NICE guidance recommends the tyrosine kinase inhibitors gefitinib, erlotinib, afatinib, dacomitinib and osimertinib as treatment options (NICE technology appraisal guidance 192, 258, 310, 595 and 654 respectively)._x000D_ _x000D_ References_x000D_ 1. National Lung Cancer Audit (2020). Royal College of Physicians. Accessed November 2021._x000D_ 2. Non-small cell lung cancer treatment. National Cancer Institute. Accessed November 2021._x000D_ 3. National Lung Cancer Audit: 2019 information sheet (for the audit period 2018) (2020). Royal College of Physicians. Accessed November 2021._x000D_ 4. Lung cancer survival statistics (2010-11). Cancer Research UK. Accessed November 2021.

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

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS
Title: Developing user interface of a novel point-of-care medical device to identify chemotherapy patients at risk of neutropenic sepsis
Funder: Department of Health and Social Care

Abstract: Neutropenic sepsis (NS) is a medical emergency that can occur in chemotherapy patients because chemotherapy suppresses neutrophils, a key infection-fighting white blood cell. By enabling patients to be triaged for NS at-home for the first time, our breakthrough point-of-care, finger-prick device, NeutroCheck, could prevent up to 50,000 A&E visits and 400 deaths in the UK each year, saving the NHS up to &pound;70m [HEE independent health economics]. NeutroCheck is supported by, and being co-created with, Macmillan Cancer Support and The UK Sepsis Trust. The device is now in the final stages of development. To achieve design freeze, we must finalise materials accompanying the NeutroCheck device: (i) Instructions for Use (IFUs), (ii) patient/healthcare professional (HCP) training materials, and (iii) packaging. As key components of the medical device interface, high usability is critical to obtaining regulatory approval and enabling clinical adoption. Following 3 formative evaluations (28 patients/carers, 5 HCPs) of early IFU iterations, there was strong demand for clearer product-related documentation, with standard written IFUs largely considered to have significant limitations. We will therefore innovate in this area, incorporating skills in human factors, graphics and information design, to build materials through user-centred design. Funding for this project will enable engagement of expert graphic designers to design final user-centred IFU, training and packaging materials, working in collaboration with Macmillan Cancer Support, and conduct of a pre-summative user-testing session with patients and HCPs. Funding is required now as (i) the NeutroCheck device design, user interface specification and risk analysis are now sufficiently-developed to enable finalisation of accompanying materials, and (ii) we do not have resource to access the skills to achieve this. The outputs of this project will enable us to reach design freeze and submit our clinical trial plans for MHRA approval, ultimately progressing toward regulatory submission for the device.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS