Frequency of Epidermal Growth Factor Receptor Mutations among Filipino Patients with Non-small Cell Lung Carcinoma

Cyril Kim Nee-Estuye-Evangelista, Jose Jasper Andal, Daphne Ang

Abstract

Background. Epidermal Growth Factor Receptor (EGFR) mutation status has been shown to have a significant prognostic and predictive role in the management of Non-small Cell Lung Carcinoma (NSCLC), significantly prolonging patients' survival. Thus, EGFR mutational analysis before initiation of treatment is now recommended in several clinical practice guidelines. Although EGFR mutation testing in NSCLC has been a part of clinical care in the Philippines, there is little data on the EGFR mutation spectrum among Filipinos.

Objective. This study aims to determine the frequency of EGFR mutations among Filipino population diagnosed with NSCLC in a private tertiary care setting.

Methodology. A total of 626 tissue samples (444 biopsies, 108 pleural/ascitic fluids, 74 excision/resection), during a 15-month period (January 2015-March 2016) were assessed for the known EGFR driver mutations (exons 18, 19, 20, 21) using the Roche EGFR protocol with the Cobas Quantitative Real Time PCR. Macrodissection was performed as necessary. Available patient demographics were recorded. Statistical analyses were performed using the Fisher's exact test.

Results. In this study, we report the largest EGFR mutation profiling data among Filipino patients with NSCLC, which showed an overall 49.4 % EGFR mutation rate. The mutation rates according to histologic types, were as follows: adenocarcinoma (49.9 %, n=287/575), squamous cell carcinoma (3.5%, n=9/26), NSCLC NOS (50 %, n=10/20), adenosquamous cell carcinoma (66.7 %, n=2/3), and adenocarcinoma with neuroendocrine features (50%, n=1/2). Consistent with the literature, we found a significant higher incidence of EGFR mutation among women than men (60.2% vs 39.8%). With regards to individual mutation types, the most common mutations detected were deletions in exon 19 (54.7 %, n=168), followed by L858R point mutation in exon 21 (27.4 %, n=84).

Conclusion. The incidence of EGFR mutations in NSCLC varies across different ethnicity. In previous reports, the frequency of EGFR mutations is approximately 30% (with a range of 22.2% to 64.2%) among the Asian population compared with 20% among the white population. In the Philippines, the incidence of EGFR mutations is sparsely explored. Here we report the largest EGFR mutation profiling data among Filipinos with NSCLC in a tertiary care setting, with a frequency of 49.4%. This prevalence is almost similar to those reported in Asia. EGFR is differentially mutated among NSCLC patients with different gender, as women have significantly higher incidence than men. Hence, this study establishes relevance of routine EGFR mutation testing for all NSCLC patients as part of initial workup at diagnosis and underscores the significant role of EGFR inhibitors as a treatment option among Filipino population.

Keywords

Epidermal growth factor receptor, non-small cell lung carcinoma, Exons 18,19,20 and 21, T790M, polymerase chain reaction

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