Non-Small Cell Lung Cancer (NSCLC)

Lung cancer at a glance

Despite the recent increase in the number of treatment options, lung cancer remains the most common cause of cancer death worldwide.^1,2

Although patient outcomes are better if the disease is diagnosed in its early stages, early diagnosis of lung cancer can present challenges.⁴ The NLCA reported that 41% of lung cancer patients diagnosed in England in 2024 presented with stage IV disease. ³

Stage at diagnosis has an impact on survival rates. Those diagnosed in England between 2015 and 2019 with stage 1 lung cancer had reported one-year survival rates of 90%, falling to 21% for those diagnosed at stage IV.⁵

Non-small cell lung cancer (NSCLC) is the most predominant subtype, accounting for approximately 85% of lung cancers.⁶ Metastatic, stage IV NSCLC is associated with poor prognosis, with the estimated 5-year survival rate less than 5%.⁴

Developments in advanced/metastatic non-squamous NSCLC treatment

Targeting driver mutations in NSCLC

One of the most significant advances in the treatment of advanced/metastatic NSCLC has been the identification and targeting of driver mutations. Several molecular drivers have been identified that represent strong predictive biomarkers and serve as therapeutic targets. Guidelines suggest that patients with advanced adenocarcinoma should be tested for the presence of oncogenic drivers that may be therapeutically targeted. This includes broad molecular profiling of EGFR, ALK, KRAS, ROS1, BRAF, NTRK1/2/3, METex14 skipping, RET, and HER2 genes.^7,8

Non-Squamous NSCLC lacking targetable driver mutations

For NSCLC without driver mutations, recent advances in various treatment lines have included immunotherapies that target the programmed cell death receptor 1 (PD-1) or programmed cell death ligand 1 (PD-L1).⁹ Treatment in patients without a targetable mutation is typically guided by the level of expression of PD-L1.¹⁰ In current treatment guidelines, anti-PD-1 and anti-PD-L1 have become a first line therapy option for patients with tumours that are PD-L1 positive ≥50% and have no other targetable driver mutations.^7,11 Combinations of chemotherapy with anti-PD-1 or anti-PD-L1 (ie chemo-immunotherapy) are an option first-line across PD-L1 levels, and platinum doublet chemotherapy remains a first-line option for patients with a PD-L1 of <50%.¹¹

Molecular diagnostics and tailored treatment in NSCLC

Alongside treatments targeted to specific mutations, diagnostic techniques that identify these mutations in patients are needed. Ideally, a diagnostic test should be sensitive, non-invasive and fast enough to inform a treatment decision. Liquid biopsy is one such technique: plasma samples, rather than tumour samples, can be analyzed for the presence of mutations.¹²

Liquid biopsy (ctDNA) testing which can detect very small fragments of circulating tumour DNA is now available for patients with suspected advanced NSCLC in England to complement other diagnostic strategies. Clinical implementation is ongoing.¹³