Title: Alectinib for untreated anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer [ID925]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of alectinib within its marketing authorisation for untreated, anaplastic lymphoma kinase-positive (ALK-positive) advanced non-small-cell lung cancer.

Lay abstract: Lung cancer falls into two main histological categories: non-small-cell lung cancers (NSCLC), which account for 85–90% of all lung cancers (1), and small- cell lung cancers. NSCLC may be grouped by tumour histology into squamous cell carcinoma, adenocarcinoma and large-cell carcinoma, with the latter 2 being collectively referred to as ‘non-squamous’ lung cancer. Anaplastic lymphoma kinase (ALK) fusion genes are chromosomal alterations that occur between the tyrosine kinase portion of the ALK gene and other genes. They are believed to be involved in the growth of tumours. ALK translocation can occur in NSCLC of any histology, although it is thought to be most common in tumours with adenocarcinoma histology (that is, non- squamous histology) and is uncommon in tumours with squamous cell carcinoma histology.(2) People with NSCLC who have an ALK fusion gene are unlikely to have epidermal growth factor receptor (EGFR) mutations. Accordingly, people with the ALK fusion gene do not usually receive drugs that inhibit EGFR tyrosine kinase, such as erlotinib and gefitinib. 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 74% had stage III or stage IV disease1. Approximately 5% of people with stage III or IV NSCLC have ALK fusion genes, equating to around 1170 people in England.(3) NICE clinical guideline 121 recommends platinum-based chemotherapy (cisplatin or carboplatin with either docetaxel, gemcitabine, paclitaxel, or vinorelbine) as a first-line treatment for people with stage III or IV NSCLC and good performance status. In current clinical practice, these combinations are used to treat squamous-cell NSCLC and not usually offered to people with non-squamous NSCLC. For non-squamous advanced NSCLC, NICE technology appraisal guidance 181 recommends pemetrexed in combination with cisplatin. 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). For people with untreated ALK-positive advanced NSCLC, NICE technology appraisal guidance 406 recommends crizotinib as an option. References 1 Royal College of Physicians (2017) National Lung Cancer Audit annual report 2016 (for the audit period 2015). Accessed July 2017 2 Scagliotti G, Stahel RA, Rosell R et al. (2012) ALK translocation and crizotinib in non-small cell lung cancer: An evolving paradigm in oncology drug development. European Journal of Cancer 48: 961-973 3 Cancer esearch UK (2014) Biological therapy for lung cancer. Accessed July 2017

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