Title: Nivolumab in combination with ipilimumab for untreated PD-L1-positive non-small cell lung cancer [ID1187]
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 non-small-cell lung cancer in adults who have a high tumour mutational burden.

Lay abstract: Lung cancer falls into 2 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 main 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 31,900 people were diagnosed with NSCLC in England, of whom 60% had stage IIIB or stage IV disease (2). Tumour mutational burden is a biomarker that reflects the total number of mutations carried by tumour cells. Tumour mutational burden is one type of biomarker that may help predict the likelihood that a person responds to immunotherapies. Cancer cells with more than 10 mutations per megabase are considered to have a high tumour mutational burden. 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- based chemotherapy (that is, cisplatin or carboplatin and either docetaxel, gemcitabine, paclitaxel, or vinorelbine) as an option for people with 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 (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). NICE technology appraisal guidance 447 recommended pembrolizumab with a managed access agreement through the Cancer Drugs Fund for people whose tumours express PD-L1 with at least a 50% tumour proportion score and have no epidermal growth factor or anaplastic lymphoma kinase- positive mutations. A review of this guidance is in progress; the Final Appraisal Determination recommends pembrolizumab for routine commissioning [ID1349]. References 1 Cancer Research UK (2017) Lung cancer incidence statistics (2011 data). Accessed February 2017. 2 Health and Social Care Information Centre (2017) National Lung Cancer Audit annual report 2016 (for the audit period 2015) 3 Cancer Research UK (2017) Lung cancer survival statistics (2014 data). Accessed February 2017.

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