THE LIVES AFFECTED BY EGFR EXON 20 INSERTION MUTATIONS

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EGFR ex20ins mutations are the third most common group of activating mutations in NSCLC, which could rob ~60,000 people around the world each year of time, hope and life[1][2][3][4][5][6][7][8][9][10]

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]

Estimated number of patients

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]

By testing for EGFR ex20ins mutations in NSCLC, you may see them more often than you think.[12]

By testing for EGFR ex20ins mutations in NSCLC, you may see them more often than you think.<sup className="footnote">12</sup>

Find out more information on how to look for EGFR ex20ins mutations.

Find out more information on how to look for EGFR ex20ins mutations.

The real-world reported frequency of EGFR ex20ins mutations varies globally, but data suggest their frequency may be underestimated – meaning many of these mutations may remain hidden[11][13][14]

The real-world reported frequency of EGFR ex20ins mutations ranges globally, accounting for 1–12% of all EGFRm NSCLC cases (fig. 2).[11]

  • A higher frequency of EGFR ex20ins mutations are observed in the USA (5–12% of EGFRm NSCLCs), Latin America (5–8% of EGFRm NSCLCs), and Europe (4–12% of EGFRm NSCLCs) – whilst lower frequencies are seen in South Asia (1–4% of EGFRm NSCLCs) (fig. 2)[11]
Figure 2. Mutations globally

Figure 2. The frequency of EGFR exon 20 insertion mutations varies globally.[11]
A systematic literature review of 53 studies* identified the frequency of EGFR ex20ins mutations globally. Testing methodologies used to identify EGFR ex20ins mutations varied, including RT-PCR/Sanger (n=16), followed by RT-PCR/Cobas (n=6), Amplification Refractory Mutation System™ (ARMS; n=6), next-generation sequencing (NGS)/capture-based comprehensive genomic profiling (n=4), and mass spectroscopy genotyping (n=2).
Adapted from Burnett H et al. 2020.[11]
*38 studies were single-centre, 14 were multicentre, and one was a meta-analysis.[11]

Variations in the reported frequency may in part be due to the differences in testing, and it is likely that the true number of patients who have EGFRm ex20ins NSCLC is underestimated.[11][13] Next-generation sequencing (NGS) is the only diagnostic method to date that can detect all known variants of EGFR ex20ins mutations – in fact, for every two EGFR ex20ins mutations detected by NGS, PCR misses one.[11][15]

Like other EGFR mutations, ex20ins mutations are particularly prevalent in:[2][13]

Non-smokers
Women
Those of Asian ethnicity
Tumours with adenocarcinoma histology

Symptoms of EGFRm ex20ins NSCLC can impact many aspects of life[16]

Patients are left physically and emotionally vulnerable, with fatigue, pain, and shortness of breath being the most commonly reported symptoms (fig. 4).[16]

Disease related symptoms

Figure 4. Disease-related symptoms in EGFRm ex20ins NSCLC.
Adapted from Bell J et al. 2018.[16]

With no specifically approved targeted therapy, patients may lose the things most precious to them…[17]

time

Time

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]

hope

Hope

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]

life

Life

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]

Discover more about NSCLC and EGFR exon 20 insertion mutations here:

How can molecular biomarkers help us fight NSCLC?
What causes EGFR-TKI resistance?
How can NGS help you to find EGFR ex20ins mutations?

* 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.

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