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Yuzhi An
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.37 - Comprehensive Investigation of Uncommon EGFR Mutations in 14,429 Chinese Lung Cancer Patients (ID 1766)
00:00 - 00:00 | Presenting Author(s): Yuzhi An
- Abstract
Introduction
Uncommon EGFR mutations are thought to be in only 10 to 20 percent of EGFR mutation cases. Most of them harbor heterogeneous molecular alterations within exons 18-21, and some of them are sensitive to EGFR TKI. However, rare specific studies have evaluated uncommon EGFR mutations in detail.
Methods
We retrospectively screened 14,429 Chinese lung cancer patients who had underwent molecular diagnosis on their tumor and/or liquid biopsy samples using hybridization-based targeted next-generation sequencing (NGS) between 2017 and 2019. Uncommon EGFR mutations as well as concurrent classical EGFR mutations in the same patient were analyzed.
Results
Here we summarized the characteristics of uncommon EGFR mutations. A total of 2,942 (20.39%) patients harbored 1,173 different uncommon EGFR mutations, among which, 1,751 patients (12.14%) carried uncommon mutations alone, without classical EGFR mutations. For 1,173 different uncommon EGFR mutations, there were 642 single mutations (SM) derived from 2098 patients (14.54%), and 531 double and multiple mutations (D/MM) from 844 patients (5.85%). The top three SM were L747_P753delinsS (172 patients, 1.19%)，L747_T751del (122, 0.85%) and L861Q (74, 0.51%), while the four most prevalent mutations of D/MM were L747_E749del;A750P (52, 0.36%), E746_S752delinsA;S752F (31, 0.21%), G719C;S768I (27, 0.19%) and G719S;S768I (22, 0.15%). Among all uncommon mutations, missense variant and in-frame deletion were identified at a frequency of 69% and 13.8%. Moreover, most of uncommon mutations were scattered throughout the exon 18-21, including the three highest frequency mutations at positions L747, E746, G719, and the frequencies in detail were summarized in Table 1. Currently, some of uncommon mutations are proved to be clinically sensitive to EGFR TKI. We collected 52 reported EGFR-TKI-sensitive uncommon mutations, and 39 of them were found in our data, among which, G719X (1.75%), L747_T751del (1.46%) and E709X (1.05%) were the main mutations. Intriguingly, we found 790 patients (5.48%) had EGFR-TKI-sensitive uncommon mutations alone, especially L747_T751del (1.10%), L861Q (0.66%) and A750P (0.51%). This group of patients (790, 5.48%) could also benefit from EGFR-TKI drugs.
ConclusionTable 1. The positions of highest frequency uncommon mutations.
Exon
Position
Frequency in exon(s)
Patients
/all lung cancer patients
Exon 1-28 (2,942 patients)
L747
22.37%
658
4.56%
E746
8.33%
245
1.70%
G719
7.78%
229
1.59%
Exon 18
(442 patients)
G719
51.81%
229
1.59%
E709
24.89%
110
0.76%
L718
4.5%
20
0.14%
Exon 19
(1,363 patients)
L747
48.3%
658
4.56%
E746
18.0%
245
1.70%
A750
10.8%
147
1.02%
Exon 20
(675 patients)
S768
24.0%
162
1.12%
C797
12.15%
82
0.57%
A767
10.52%
71
0.49%
Exon 21
(364 patients)
L861
36.3%
132
0.91%
L833
19.0%
69
0.48%
V834
6.9%
25
0.17%
More and more uncommon EGFR mutations are identified owing to the development of NGS. This is the largest NGS-based cohort of Chinese lung cancers for investigating uncommon EGFR mutations, and 5.48% patients that with EGFR-TKI-sensitive uncommon mutations alone were found, which should be informative for the clinical therapies.
