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).[3][4][5][6][7]
Around 10% of these patients have an added challenge – they harbour insertion mutations in exon 20 of their EGFR gene (fig. 1).[1][2][3][4][6][7][8][9][11] This represents around 60,000 patients every year (fig. 1).[1][2][3][4][5][6][7][8][9]
Figure 1. Estimated number of patients with NSCLC with an EGFR exon 20 insertion mutation in their tumour, each year globally.[1][2][3][4][5][6][7][8][9]
Patients are left physically and emotionally vulnerable, with fatigue, pain, and shortness of breath being the most commonly reported symptoms (fig. 4).[16]
Figure 4. Disease-related symptoms in EGFRm ex20ins NSCLC.
Adapted from Bell J et al. 2018.[16]
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).[18] The precious time that patients have left is often tainted by the negative emotional burden of the disease.†,[16]
Patients with EGFRm ex20ins NSCLC generally experience limited outcomes with currently approved EGFR-TKIs.[1][2] 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.‡,[8]
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.[19][20][21][22]
* 38 studies were single-centre, 14 were multicentre, and one was a meta-analysis.[11]
** 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.[16]
‡ 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.[8] Mean ORR of patients with EGFRm NSCLC, without a detectable ex20ins mutation to EGFR-TKIs=34.0% (13.9–84%).[8] Mean ORR of patients with EGFRm ex20ins NSCLC to EGFR-TKIs=11.9% (0.0–35.0%).[8]
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.
CP-223640