Title: Nivolumab with chemotherapy for neoadjuvant treatment of resectable non-small cell lung cancer [ID3757]
Funder: Department of Health and Social Care

Abstract: Lung cancer is the third most common cancer and the most common cause of cancer death in the UK, accounting for 13% of all new cancer cases and 21% of all cancer deaths in 2017. [1] There are around 38,900 new lung cancer cases and 27,700 deaths from lung cancer in the England every year. Up to 85% of lung cancers are nonsmall-cell lung cancers (NSCLC).[2]_x000D_ _x000D_ 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). Less than 30% of lung cancers are diagnosed at an early stage (stage I or II)._x000D_ _x000D_ NICE guideline Lung cancer: diagnosis and management (NG122) recommends surgery, radiotherapy, chemotherapy or a combination of these for early stage disease.[3] Around 15% of people with NSCLC had surgical resection with curative intent in England in 2020. [4] For people with stage I–II NSCLC that are suitable for surgery, neoadjuvant (before surgical removal of cancerous tumour) treatment is not currently recommended by NICE guideline NG122 outside a clinical trial[3] . Neoadjuvant chemotherapy has shown equivalent outcomes in terms of survival to adjuvant chemotherapy.[5] For stage III NSCLC, surgery is carried out if the surgeon deems the tumour to be excisable. Before surgery, chemoradiotherapy may be given (chemotherapy with radiotherapy) or surgery may potentially be followed by chemotherapy.[3] If surgery is not possible, patients may undergo treatments including chemoradiotherapy which may be followed by immunotherapy. If well enough, people may be offered a cisplatin-based chemotherapy (adjuvant treatment) after surgery.[3] People are actively monitored for cancer recurrence. If the cancer comes back, treatment options and prognosis depend on the site of the recurrence. Despite the curative intent of treatment for early-stage lung cancer, survival is poor, with only about 57% people with stage I, 34% with stage II and 13% with stage III surviving for 5 years after diagnosis.[6] TA761 recommends osimertinib for use within the Cancer Drugs Fund as adjuvant treatment after complete tumour resection in adults with stage IB to IIIA NSCLC whose tumours have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. _x000D_ _x000D_ It is estimated that over half of all NSCLCs express the programmed cell death ligand-1 (PD-L1) biomarker.7 Cancer cells expressing PD-L1 are believed to suppress certain immune responses and cause increased tumor aggressiveness._x000D_ _x000D_ References_x000D_ 1. Lung cancer statistics. Cancer Research UK. Accessed April 2022_x000D_ 2. Types of lung cancer. Cancer Research UK. Accessed April 2022_x000D_ 3. Lung cancer: diagnosis and management. (2019) NICE guideline 122_x000D_ 4. National Lung Cancer Audit: Annual report 2022 (for the audit period 2020). Royal College of Physicians. Accessed May 2022_x000D_ 5. European Society for Medical Oncology (ESMO). Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2017;28(Supplement 4):iv1–iv21. Available from: https://www.esmo.org/Guidelines/Lung-andChest-Tumours/. Accessed April 2022_x000D_ 6. Office for National Statistics. Cancer Survival in England: adults diagnosed between 2013 and 2017 and followed up to 2018. 2019. Available from:_x000D_ https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancersurvivalratescancersurvivalinenglandadultsdiagnosed. Accessed April 2022_x000D_ 7. Skov, B., Rørvig, S., Jensen, T. et al. (2020) The prevalence of programmed death ligand-1 (PD-L1) expression in non-small cell lung cancer in an unselected, consecutive population. Mod Pathol 33, 109–117

Lay abstract: To appraise the clinical and cost effectiveness of nivolumab with chemotherapy within its marketing authorisation for neoadjuvant treatment of resectable non-small cell lung cancer.

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