Cemiplimab with chemotherapy for untreated advanced or metastatic non-small-cell lung cancer (ID3949)

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 between 2017 and 2019.1 Most lung cancers are diagnosed at an advancedstage when the cancer has spread to lymph nodes and other organs in the chest (locally advanced disease; stage 3) or to other parts of the body (metastatic disease; stage 4).

Around 30% of lung cancers are diagnosed at an early stage (stage 1 or2).2In 2021 91% (around 31000) of people diagnosed with lung cancer in England had NSCLC.2 Of these people 17% (5333) had surgical treatment for their cancer.2 Despite the curative intent of treatment for early-stage lung cancer survival is poor with only about 57% people with stage 1 34% with stage 2 and 13% with stage 3 surviving for 5-years after diagnosis.3 It is estimated that over half of all NSCLCs express the programmed cell death ligand-1 (PD-L1) biomarker.4 Cancer cells expressing PD-L1 are believed to suppress certain immune responses which results in a weaker anti-tumour response.45The treatment pathway for NSCLC can be divided into interconnected decision points based on the number staging system and line of therapy.

Treatment choices are influenced by the presence of biological markers (including programmed cell death 1 ligand PD-L1 status) oncogenic driver genetic alterations histology (squamous or non-squamous) and previous treatment.NICE guideline 122 (NG122) ‘Lung cancer: diagnosis and management’ recommends surgery radiotherapy chemoradiotherapy or a combination of these for stage 1 to 2 NSCLC.

People may be offered a neo-adjuvant (before surgical removalof cancerous tumour) treatment which could be nivolumab with chemotherapy as recommended by TA876 or may be offered platinum based chemotherapy as neoadjuvant or adjuvant treatment.For untreated metastatic non-squamous NSCLC people may be offered pembrolizumab with pemetrexed and platinum chemotherapy (TA683) or pemetrexed and platinum chemotherapy irrespective of PD-L1 expression (based on clinicalopinion).

If the non-squamous NSCLC expressed PD-L1 on less than 50% of tumour cells people may be offered atezolizumab plus bevacizumab carboplatin andpaclitaxel (TA584) or pemetrexed with platinum doublet chemotherapy.

If the nonsquamous NSCLC expressed PD-L1 on over 50% of tumour cells they may be offered pembrolizumab (TA531) or atezolizumab (TA705) monotherapy.For untreated squamous NSCLC people may be offered pembrolizumab with carboplatin and paclitaxel (TA770) if the NSCLC expresses PD-L1 on less than 50% of cells or on over 50% of cells if there is a need for urgent clinical intervention.

If thesquamous NSCLC expresses PD-L1 on 50% or more of its tumour cells people may be offered pembrolizumab (TA531) or atezolizumab (TA705) monotherapy. People may also be offered chemotherapy (based on clinical opinion).References1. Cancer Research UK (2023). Lung cancer statistics. Accessed October 2023.2.

Royal College of Surgeons of England (2023). National Lung Cancer Audit: State of the Nation Report 2023. Accessed November 2023.3. Office for National Statistics. Cancer Survival in England: adults diagnosed between 2013 and 2017 and followed up to 2018. 2019.

Available from:https://www.ons.gov.uk/peoplepopulationandcomunity/healthandsocialcare/conditionsanddiseases/datasets/cancersurvivalratescancersurvivalinenglaadultsdiagnosed. Accessed October 2023.4. 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 33 109–117.5. Han Y Liu D Li L. PD-1/PD-L1 pathway: current researches in cancer. Am J Cancer Res. 2020 Mar 1;10(3):727-742. PMID: 32266087; PMCID: PMC7136921.