Title: Brigatinib after crizotinib for treating ALK-positive advanced non-small-cell lung cancer after crizotinib [ID1328]
Funder: Department of Health and Social Care

Abstract: To appraise the clinical and cost effectiveness of brigatinib within its marketing authorisation for treating advanced ALK-positive non-small-cell lung cancer after treatment with crizotinib.

Lay abstract: Lung cancer falls into two main histological categories: non-small-cell lung cancers (NSCLC), which account for 88% 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 (almost exclusively) with adenocarcinoma histology (that is, non-squamous histology) which represent 36% of NSCLC patients and is uncommon in tumours with squamous cell carcinoma histology.(1),(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, gefitinib and afatinib. 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 disease.(3) Approximately 5% of people with stage III or IV non-squamous (adenocarcinoma) NSCLC have ALK fusion genes, equating to around 1170 people in England & Wales.(4) 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 EGFR-TK, ALK or PD- L1 status, histology (squamous or non-squamous) and previous treatment experience. NICE technology appraisal guidance 395 recommends ceritinib as a treatment option for treating advanced anaplastic lymphoma kinase positive non-small-cell lung cancer in adults who have previously had crizotinib. References 1. Royal College of Physicians (2017) National Lung Cancer Audit Report 2016 (for the audit period 2015). Accessed October 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. Office for National Statistics (May 2017) Cancer Statistics Registrations, England: 2015. Accessed October 2017 4. Cancer Research UK (2014) Biological therapy for lung cancer. Accessed October 2017

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