NSCLC and its three main histological sub-types (adenocarcinoma, squamous cell carcinoma and large cell carcinoma) account for the majority (~85%) of lung cancer cases
Around 60% of all patients with NSCLC have metastatic disease at the time of diagnosis. Although the exact reasons are unclear, this may in part be due to the late presentation of symptoms, which means the disease is detected too late, delays in patients seeking medical care, or delays in the diagnostic process.
The late presentation of lung cancer ultimately leads to a poor prognosis, where the 5-year survival drops from 68% in stage 1B to 0–10% in stage 4A–4B.
Figure 1. Subtypes of lung cancer and NSCLC, including the three main NSCLC histological classifications.
The cells of origin and smoking status are indicated for each of the three main histological sub-types of NSCLC.
Adapted from Lemjabbar-Alaoui H et al. 2015.
The management strategy for locally advanced/metastatic NSCLC should consider several factors such as tumour histology, patient age, performance status, comorbidities, the patient's preference, and, importantly, the tumour’s molecular pathology.
Two testing streams are commonly used to identify patients who may benefit from targeted therapies. These tests are used to detect (fig.2):
Figure 2. Stage IV NSCLC treatment options.*
Targeted therapies may be available to patients who have a detectable mutation in EGFR, ALK, BRAF V600, and ROS1. PD-L1 expression should be assessed in those tumours that do not have a detectable biomarker, and these patients should be treated according to clinical practice guidelines.
Adapted from the ESMO clinical practice guidelines, 2020.
The European Guidelines state that EGFR testing should assess all mutations of exons 18 to 21, including at a minimum the most common activating mutations (exon 19 deletion and exon 21 L858R point mutation).
EGFR exon 20 insertion (ex20ins) mutations are generally resistant to currently approved EGFR-TKIs – so if these mutations are detected, platinum-based chemotherapies are often prescribed as a first-line therapy.
* Not all therapies are approved by the European Medicines Agency; please refer to local management guidelines for the recommendations in your area.
ALK, anaplastic lymphoma kinase; BRAF, v-Raf murine sarcoma viral oncogene homolog B; CD74, Cluster of Differentiation 74; EGFR, epidermal growth factor receptor; FISH, fluorescence in-situ hybridisation; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; KRAS, Kirsten rat sarcoma viral oncogene homologue; MEK, mitogen-activated protein kinase kinase; MPRIP, myosin phosphatase RHO-interacting protein; nab-P, albumin-bound paclitaxel; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; PCR, polymerase chain reaction; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; PI3K, phosphoinositide 3-kinase; PS, performance status; RET, rearranged during transfection; ROS1; ROS proto-oncogene 1, receptor tyrosine kinase; RT-PCR, reverse transcription polymerase chain reaction; TMB, tumour mutation burden.