Award Title: Lorlatinib for untreated ALK-positive advanced non-small-cell lung cancer [ID3896] - Part 2
Funder: Department of Health and Social Care

Abstract: Lung cancer falls into two main groups: around 80 to 85% are non-small-cell lung cancers (NSCLC) and the remainder are small cell lung cancers. [1] 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 adenocarcinoma. [2] 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 2018, 39,754 people were diagnosed with NSCLC in England & Wales. Of these people, 49% had stage IV disease and 12% had stage IIIB/C. [3]_x000D_
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Lung cancer caused over 35,000 deaths in the UK between 2016-2018. [4] Forty-five percent of people with lung cancer survive for more than 1 year after diagnosis. [5]_x000D_
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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 (almost exclusively) in tumours with adenocarcinoma histology. Approximately 3–7% of all lung tumours contain ALK mutations[6]._x000D_
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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, ROS-1 or BRAF, or levels of PD-L1 expression), histology (squamous or non-squamous) and previous treatment experience. People with confirmed ALK-positive NSCLC are likely to be offered initial treatment with ALK-targeted treatment. NICE recommends crizotinib (TA406), ceritinib (TA500), alectinib (TA536) and brigatinib (TA670) as treatment options for adults with untreated ALK-positive advanced NSCLC. People with NSCLC of an unknown ALK status may be offered initial treatment with platinum-doublet chemotherapy._x000D_
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References_x000D_
1 Types of lung cancer. Cancer Research UK. Accessed February 2021._x000D_
2 Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2016, National Cancer Institute. [Available from: https://seer.cancer.gov/csr/1975_2016/ ]. Accessed February 2021._x000D_
3 National Lung Cancer Audit annual report (for the audit period 2018) (2020). Royal College of Physicians. Accessed February 2021._x000D_
4 Lung cancer mortality statistics (2018). Cancer Research UK. Accessed February 2021._x000D_
5 Lung cancer survival statistics (2013 - 2017). Cancer Research UK. Accessed February 2021._x000D_
6 Zappa C, Mousa S (2016). Non-small cell lung cancer: current treatment and future advances. Translational Lung Cancer Research. Accessed February 2021.

Lay Abstract: To appraise the clinical and cost effectiveness of lorlatinib within its marketing authorisation for untreated ALK-positive advanced non-small cell lung cancer.

Research Activity Codes: 6.1 PHARMACEUTICALS
Health Categories: CANCER AND NEOPLASMS