Title: Atezolizumab for untreated non-squamous non-small-cell lung cancer [ID1210]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of atezolizumab in combination within its marketing authorisation for treating advanced non-squamous non-small-cell lung cancer.

Lay abstract: Lung cancer falls into 2 main histological categories: 85-90% are non-small-cell lung cancers (NSCLC) and 10-15% are small-cell lung cancers1. NSCLC can be further classified into squamous cell carcinoma and non-squamous cell carcinoma. Approximately 70% of NSCLC are of non-squamous histology and can be either large-cell undifferentiated carcinoma or adenocarcinoma2. 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 2016, approximately 32,500 people were diagnosed with NSCLC in England, and around 61% had stage IIIB or stage IV disease3. Lung cancer caused over 35,620 deaths in England in 20164. Thirty two percent of people with lung cancer survive for more than 1 year after diagnosis5. 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 or large-cell carcinoma (NICE TA 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 TA 190 and 402). For untreated, advanced, non-squamous NSCLC that is epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation-positive, people may receive afatinib (NICE TA 310), erlotinib (NICE TA 258) or gefitinib (NICE TA 192).For untreated, advanced, non-squamous NSCLC that is anaplastic lymphoma kinase (ALK)-positive, people may receive ceritinib (NICE TA 500) or crizotinib (NICE TA 406). For people whose disease has progressed after targeted treatment, options include docetaxel and pembrolizumab (NICE TA 520). 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 Lung cancer incidence by morphology. Cancer Research UK. Accessed July 2018 2 Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, et al. SEER Cancer Statistics Review, 1975-2012, National Cancer Institute. 2015 [Available from: https://seer.cancer.gov/csr/1975_2012/. 3 National Lung Cancer Audit: Annual report 2017 (for the audit period 2016) (2018). Royal College of Physicians. Accessed July 2018. 4 Lung cancer mortality statistics (2016). Cancer Research UK. Accessed July 2018. 5 Lung cancer survival statistics (2010-11). Cancer Research UK. Accessed July 2018.

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