Global Incidence and Prevalence of EGFR-Mutated Non-Small Cell Lung Cancer

Recent studies indicate that the incidence of EGFR mutations in non-small cell lung cancer (NSCLC) varies significantly according to ethnic and geographical backgrounds. EGFR mutations represent the most common type of oncogenic drivers in NSCLC patients globally.

Regional Variation

Asian populations consistently demonstrate a high prevalence of EGFR mutations. A 2023 study reported that among Asian NSCLC patients, 43.3% (103 out of 238 cases) harbored EGFR mutations. Similarly, in Yunnan province, China, the overall EGFR mutation rate was 34.9%, with variation depending on sample type (42.3% in tissue samples, 29.7% in plasma samples).

In Algeria, a 2021 study found EGFR mutations in 39.6% of NSCLC patients, noting this rate was more similar to Asian than Caucasian populations.

New Zealand data (2010-2017) showed that among 3,815 non-squamous NSCLC patients, 45% were tested for EGFR mutations, with 22.5% testing positive. The age-standardized rate (ASR) of EGFR mutation-positive NSCLC was 5.05 per 100,000 person-years, while EGFR mutation-negative NSCLC had an ASR of 17.39 per 100,000 person-years.

In Turkey, EGFR mutations accounted for 69.9% of all detected mutations, with an overall mutation positivity rate of 18.9% among NSCLC patients. This rate was comparable to East European, African-American, and Caucasian patients, but lower than in East Asia.

Iraqi NSCLC patients showed an EGFR mutation rate of 27.53%, positioned between the higher rates in Asian populations and lower rates in Western countries.

Demographic Factors

Several demographic factors influence EGFR mutation prevalence:

• Gender: EGFR mutations are significantly more common in females than males (57.4% vs 31.5% in one study; standardized incidence ratio [SIR] 1.50 in New Zealand)

• Smoking status: Non-smokers have substantially higher rates than smokers (56.8% vs 25.9%), with never-smoking identified as an independent favorable factor for EGFR mutations

• Histology: Adenocarcinoma shows markedly higher mutation rates compared to other histological types (48.3% vs 3.7%; 51.8% vs 21.4% in the Algerian study)

• Ethnicity: In New Zealand, EGFR mutations were more prevalent in Pacific Islanders (SIR 3.47), Asians (SIR 3.35), and Māori (SIR 2.02) compared to New Zealand Europeans

Mutation Patterns

The most common EGFR mutation sites are exons 19 and 21, with frequencies of 20.6% and 19.3% respectively in one Asian study. In Algeria, 91.3% of mutations were exon-21 L585R single mutations, while 8.7% had dual mutations. In Iraq, exon 19 deletions (65.8%) and L858R in exon 21 (26.3%) were most common.

Interestingly, Xuanwei region in China showed a distinctly different EGFR mutation spectrum, with higher G719X and G719X+S768I mutations but lower exon 19 deletion and L858R mutations.

Patients with EGFR mutation-positive advanced NSCLC demonstrate better progression-free survival (PFS) and overall survival (OS) compared to those with wild-type EGFR.

Expanded Indications for RYBREVANT® and LAZCLUZE® Beyond EGFR Exon 20 NSCLC

Based on the available information, RYBREVANT® (amivantamab-vmjw) is being explored for expanded use within EGFR-mutated NSCLC beyond its current approved indication for EGFR Exon 20 insertion mutations. The clinical evidence shows:

RYBREVANT® (amivantamab-vmjw) Expanded Indications

• Classical EGFR mutations: A real-world multi-center analysis demonstrated 36.4% clinical response rate and 48.5% disease control rate in 39 patients
• Atypical EGFR mutations: Showed promising results with 85.7% clinical response rate and 100% disease control rate in 7 patients
• Combination therapy: The combination of osimertinib with amivantamab has been studied and reported as safe and feasible
• Concurrent treatment: Radiation therapy appears safe when administered sequentially or concurrently with amivantamab

LAZCLUZE® (lazertinib) Expanded Indications

Lazertinib, a third-generation EGFR tyrosine kinase inhibitor, is being investigated for:

• T790M-mutated NSCLC: In patients previously treated with an EGFR-TKI, showing 62.1% objective response rate and 94.2% disease control rate
• Brain metastases: Demonstrated efficacy with 93.5% intracranial disease control rate and 57.6% intracranial objective response rate
• First-line therapy: Being studied as initial treatment for EGFR-mutated NSCLC compared to gefitinib, showing significant PFS benefit

While both medications remain focused on EGFR-mutated NSCLC, they are being investigated for expanded use within this disease category, targeting different mutation subtypes and treatment settings beyond their original approved indications.

The specific intervention models for these trials are not detailed in the available information beyond the described treatment approaches and combinations mentioned above.