Title: Pembrolizumab for untreated PD-L1 positive metastatic non-small cell lung cancer (CDF review of TA447)[ID1349]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of pembrolizumab within its marketing authorisation for untreated PD-L1 positive metastatic 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 2013, approximately 26,800 people were diagnosed with NSCLC in England, of whom 13% had stage IIIA, 10% had stage IIIB and 46% had stage IV disease (2). Cancer cells expressing an immunologic marker called programmed cell death 1 ligand (PD-L1) are believed to suppress certain immune responses and cause increased tumour aggressiveness. The proportion of NSCLC that is PD-L1 positive in England is unknown. The median survival of people with lung cancer (all stages) is approximately 8 months (2). Around a third of people with lung cancer, and a fifth of people with stage IV disease, survive for more than 1 year after diagnosis (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 (CG121) recommends platinum-based 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 people who are unable to tolerate a platinum combination, the clinical guideline recommends single-agent chemotherapy with docetaxel, gemcitabine, paclitaxel, or vinorelbine. Best supportive care may be considered for some people for whom chemotherapy is unsuitable or may not be tolerated. 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 draft final NICE guidance from the review of technology appraisal 309 [CDF rapid reconsideration process]). References 1 Cancer Research UK (2011 data) Lung cancer incidence statistics. Accessed May 2016. 2 Health and Social Care Information Centre (2014) National Lung Cancer Audit: 2013 patient cohort. Accessed May 2016. 3 Cancer Research UK (2010–12 data) Lung cancer survival statistics. Accessed May 2016.

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