EPIDERMAL GROWTH FACTOR RECEPTOR MUTATION
STATUS AND THE IMPACT ON CLINICAL OUTCOMES
IN PATIENTS WITH NON-SMALL CELL LUNG CANCER
Huang HM1, Wei Y1, Wang JJ1, Ran FY1, Wen Y2, Chen QH3, Zhang BF1,*
*Corresponding Author: Dr. Bingfei Zhang, Sinopharm Dongfeng General Hospital, Hubei University
of Medicine, No. 16 Daling Road, 442008, Shiyan, Hubei, China. Tel.: + 86-29-8272597,
Email: dfzyysszx@163.com
page: 29
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DISACUSSION
Many studies have been carried out to estimate EGFR
mutation status among NSCLC patients in different regions
and populations in order to evaluate the benefits
from EGFR-TKI. Results showed that EGFR mutation
frequency possesses variability based on ethnicity and
regional differences, with 36.3% of positivity in Korea
[10], 13.6% in Spain [3], 10.6% in Poland [11], 15.7% in
Greece [12], 36.7% in Iran [13], 11.9% in Lebanon [14],
and greater in Japan with 53.9% [15]. The prevalence of the EGFR mutations in our study is 43.3%, lower than that
reported in a large Asian study including Chinese patients
with NSCLC (50.2%) [16], however, it is higher than that
which was reported in a multi-center diagnostic survey
carried out in the Asia Pacific Region (38.1%) [17]. In
general, the frequencies of EGFR mutations in patients
from Asian countries are quite high, even up to 68.5%
in female non-smokers with adenocarcinoma [18]. The
most common mutations detected in the present study are
exons19 and 21 (21.0% and 19.3%, respectively). 19-Del
mutation and L858R mutation were the most common
mutation types for exons 19 and 21, which was in line
with previous literature [19].
The median PFS and OS for patients with EGFR
mutations were 11 months and 24 months, respectively,
while patients with wild type EGFR demonstrated a median
4-month PFS and 12-month OS. The results show
prominent benefits in patients with EGFR mutations compared
to those with wild type EGFR. Correlations between
EGFR mutations and improved PFS and survival in EGFR
mutation-positive patients with administration of EGFRTKI
have been reported, while PFS and survival differ due
to exon mutation sites. Exons 19 and 21 mutations were
associated with sensitivity to EGFR-TKI and it has been
reported that the 19-Del mutation was associated with a
better response than the L858R mutation when patients
were treated with TKI [20, 21]. Mutations in exon 18,
including G719A, G719C, and G719S, were also drug sensitizing
mutations, however, T790M and 20-Ins mutations
had been demonstrated to confer resistance to EGFR-TKI.
In the present study, one patient with 20-Ins mutation was
observed by the authors. When compared with sensitizing
EGFR mutations, the 20-Ins mutation case failed to
respond to a combination of pemetrexed and cisplatin
and demonstrated a poor prognosis, with only a 3-month
survival. The inclusion of patient with 20-Ins mutation
resulted in a lower PFS and OS compared to patients with
sensitizing EGFR mutations, however this inclusion did
not seem to adversely affect overall PFS or OS due to the
limited numbers of patients included. Studies reported
that T790M was the most common mutant type in exon
20 [22], and in the present study, T790M point mutation
was detected in one sample together with 19-Del mutation.
Namely, the patient had a rare combination of exon
19 sensitizing mutation and T790M resistance mutation.
The mutations are heterogeneous and the EGFR-TKI efficacy
in patients with heterogeneous mutations requires
individual assessment [23, 24]. Limited to the present
study, the patient with heterogeneous mutations received
icotinib therapy and demonstrated similar treatment outcomes,
compared to sensitizing EGFR mutations, with a
14-month PFS and 23-month survival.
Studies have shown that female, no-smoking status,
adenocarcinoma histology, and Asian ethnicity are all
favorable factors for EGFR mutations [25, 26]. Similar
results were observed in the present study. The statistical
analysis showed that the EGFR mutation rate was much
higher in female than in male. The reasons for the effect
of gender on EGFR mutation rate remained incompletely
understood. Differential smoking habits and sex hormones
might contribute to the effect [27]. There were more EGFR
mutations in positive cases than in never smokers compared
with current smokers or former smokers. In the present
study, the EGFR mutations were found in 56.8% (75/132)
patients who had never smoked and in 25.9% (15/58) current
smokers (p <0.001). Likewise, the difference in EGFR
mutation rate between NSCLC patients with adenocarcinoma
and non-adenocarcinoma was significant (p <0.001).
Indeed, molecular testing guidelines recommend EGFR
testing to all advanced patients with adenocarcinoma to
guide selection of EGFR-TKI therapy, regardless of gender,
race, smoking status, or other clinical risk factors [28].
In conclusion, the EGFR mutation rate is 43.3%
among all NSCLC patients and the mutations are more
frequently observed in exons 19 and 21. EGFR mutations
are prevalent in patients who are female, have adenocarcinoma,
and have never smoked. Advanced EGFR mutationpositive
patients have longer PFS and OS than those with
wild type EGFR. But this study has some limitations such
as a relatively small number of selected cases and having
been a single-center study. Therefore, a larger sample size
and multi-center investigations are necessary to make the
research results more comprehensive and convincing.
Declaration of Interest: The authors report no conflicts
of interest. The authors alone are responsible for the
content and writing of this article.
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