Approximately one third of the 1.8 million patients worldwide who are diagnosed with NSCLC each year have an EGFR mutation (EGFRm) in their tumour, equating to 600,000 people (fig. 1).
Around 10% of these patients have an added challenge – they harbour insertion mutations in exon 20 of their EGFR gene (fig. 1). This represents around 60,000 patients every year (fig. 1).
Figure 1. Estimated number of patients with NSCLC with an EGFR exon 20 insertion mutation in their tumour, each year globally.
Patients are left physically and emotionally vulnerable, with fatigue, pain, and shortness of breath being the most commonly reported symptoms (fig. 4).
Figure 4. Disease-related symptoms in EGFRm ex20ins NSCLC.
Adapted from Bell J et al. 2018.
Patients who have EGFRm ex20ins NSCLC have a 75% increased risk of death (HR=1.75) compared to patients who have common EGFR-tyrosine kinase inhibitor (EGFR-TKI) sensitive mutations in their tumours** (median OS 16.2 vs 25.5 months, respectively). The precious time that patients have left is often tainted by the negative emotional burden of the disease.†,
Patients with EGFRm ex20ins NSCLC generally experience limited outcomes with currently approved EGFR-TKIs. In fact, response rates of these patients to EGFR-TKIs are approximately one third of those observed in patients who have EGFRm NSCLC without an ex20ins mutation.‡,
Due to the lack of effective targeted options, patients with EGFRm ex20ins NSCLC are most commonly prescribed chemotherapies as a first-line treatment, which are non-selective and have a wide range of side effects.
* 38 studies were single-centre, 14 were multicentre, and one was a meta-analysis.
** EGFR-TKI sensitive mutations: L858R or exon 19 deletions.
† Qualitative interviews conducted with patients with NSCLC with EGFR exon 20 mutations (n=10), 90% of whom had exon 20 insertion mutations. 100% of participants with EGFRm ex20ins NSCLC reported a psychological or emotional burden of their disease, and 60% described worries around treatment, the future, or finances.
‡ Data taken from a meta-analysis of 61 studies, 12 of which reported overall response rate (ORR) in patients with EGFRm ex20ins NSCLC. Patient numbers not reported. Mean ORR of patients with EGFRm NSCLC, without a detectable ex20ins mutation to EGFR-TKIs=34.0% (13.9–84%). Mean ORR of patients with EGFRm ex20ins NSCLC to EGFR-TKIs=11.9% (0.0–35.0%).
EGFR, epidermal growth factor receptor; EGFRm, mutated EGFR; ex20ins, exon 20 insertion mutations; EGFR-TKI, EGFR tyrosine kinase inhibitor; HR, hazard ratio; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; PCR, polymerase chain reaction.