Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review

Abstract

Objectives The burden of epidermal growth factor receptor (EGFR) exon 20 insertion mutation (Exon 20ins) in non-small cell lung cancer is not well understood. A systematic review was conducted to identify evidence on mutation frequency, prognostic impact, clinical, patient-reported, and economic outcomes associated with Exon 20ins. Materials and methods Searches were conducted in Embase and Medline and supplemented with recent conference proceedings. Included studies were not limited by intervention, geography, or publication year. Results Seventy-eight unique studies were included; 53 reporting mutation frequency, 13 prognostic impact, 36 clinical outcomes, and one humanistic burden. No economic burden data were identified. The frequency of Exon 20ins mutation ranged from 0.1% to 4% of all NSCLC cases and 1% to 12% of all EGFR mutations. Data on the prognostic impact of Exon 20ins were heterogeneous but highlighted poorer outcomes in patients with Exon 20ins mutation compared with patients with other EGFR mutations and EGFR wildtype across a wide range of therapies and treatment lines. Comparative evidence on the clinical efficacy and safety of currently available therapies were limited, as were sample sizes of studies reporting on real-world effectiveness. Nine single-arm trials and 27 observational studies reported clinical outcomes for patients with Exon 20ins. Trends towards better survival and response were observed for chemotherapy compared with TKIs as first-line treatments. For subsequent treatment lines, novel targeted therapies provided encouraging preliminary responses while results for chemotherapy were less favorable. Limited safety data were reported. One conference abstract described the symptom burden for Exon 20ins patients with fatigue and pain being most common. Conclusion Findings of the systematic review show a high unmet need for safe and efficacious treatments for patients with Exon 20ins as well and need for further evidence generation to better understand the patient-level and economic impact for these patients.

Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

“…Triple or more compound mutations are categorized within the four subgroups according to the presence or absence of uncommon or de novo exon 20 p.T790M mutations. Additionally, despite the known negative prognostic and predictive role with EGFR TKIs of EGFR exon 20 insertions [ 21 , 22 , 23 ], these mutations are accounted as uncommon mutations and not as separate group because of not consistent systematic reporting on compound mutations in this specific subgroup.…”

Pembrolizumab and chemotherapy in non‐small cell lung cancer with EGFR ex20ins mutation: A case report

“…EGFR exon 20 insertions (EGFR ex20ins) are an uncommon EGFR mutation type, accounting for about 0.1% to 4% of all cases of NSCLC 7 . The median PFS in these patients has been reported to be only 2 months (95% CI: 0.00–5.41) 1,8,9 .…”

Discovery, Development, Inventions, and Patent Trends on Mobocertinib Succinate: The First-in-Class Oral Treatment for NSCLC with EGFR Exon 20 Insertions

“…Oncogenes, for example, EGFR genes, have been identified in NSCLC patients. Therefore, the NSCLC is treated based on the oncogene mutations [ 65 , 66 , 67 ]. Many EGFR inhibitors are available in the market to treat NSCLC with common mutations [ 9 , 10 , 11 , 12 , 13 , 14 , 68 ].…”