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Association details:
Biomarker:EGFR exon 19 deletion
Cancer:Non Small Cell Lung Cancer
Drug Class:EGFR inhibitor
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: B - Late Trials
Source:
Title:

67P-Distinct concomitant genetic alterations in EGFR-mutant non-small cell lung cancer patients with brain metastases

Published date:
03/23/2022
Excerpt:
A total of 2657 NSCLC patients with brain metastases were screened and 737 harboring EGFR mutation, among 73 patients with NGS data, all receiving EGFR TKI treatment…As shown in the nomogram, a higher total score was associated with having EGFR 19 del mutations and without concomitant alterations indicated a higher like-lihood of longer OS.
DOI:
https://doi.org/10.1016/j.annonc.2022.02.076
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

EGFR tyrosine kinase inhibitors (TKIs) versus durvalumab (durva) following concurrent chemoradiation (CRT) in unresectable EGFR-mutant non-small-cell lung cancer (NSCLC).

Published date:
05/25/2023
Excerpt:
We conducted a multi-institutional retrospective analysis of pts with stage III unresectable EGFRmut NSCLC (exon19 deletion, exon21 L858R), who received EGFR TKI or durva after ≥ 2 cycles of platinum-based chemotherapy plus definitive radiation therapy between 2015-2022....EGFR TKI therapy after definitive CRT was associated with significantly longer DFS compared to durva in this retrospective study of pts with stage III unresectable EGFRmut NSCLC, without unanticipated safety signals.
DOI:
10.1200/JCO.2023.41.16_suppl.8567
Evidence Level:
Sensitive: C3 – Early Trials
Title:

EGFR-TKIs plus stereotactic body radiation therapy (SBRT) for stage IV Non-small cell lung cancer (NSCLC): A prospective, multicenter, randomized, controlled phase II study

Published date:
04/25/2023
Excerpt:
Eligible patients were histologically confirmed to have NSCLC with an EGFR-sensitive mutation (19DEL or 21L858R) and diagnosed at stage IV….The median PFS of the EGFR-TKI group and SBRT combination group was 9.0 vs 17.6 months (hazard ratio [HR] = 0.52, 95% confidence interval [95%CI], 0.31-0.89, P = 0.016). Meanwhile, the median OS was 23.2 vs 33.6 months (HR [95%CI], 0.53(0.30-0.95); P = 0.026)....The addition of SBRT significantly delayed the onset of acquired resistance to EGFR-TKIs and prolonged the PFS and OS of patients.
DOI:
https://doi.org/10.1016/j.radonc.2023.109681
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

30P - Real-world disease characteristics and treatment patterns in patients with advanced non-small cell lung cancer and EGFR in Brazil and Taiwan

Published date:
03/23/2023
Excerpt:
Pts with EGFRm generally received EGFR TKI mono, including those with exon 21 and exon 19. Exon 21 pts had longer TTD and rwPFS (no formal comparison was made between groups).
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Efficacy and safety of EGFR‑TKIs plus Shenqi Fuzheng injection for non-small cell lung cancer patients with EGFR-sensitive mutations

Published date:
08/26/2022
Excerpt:
...for NSCLC patients with EGFR-sensitive mutations (Exon19 Del, L858R), patients treated with co-administration of EGFR-TKIs with SFI achieve more prolonged clinical benefit and longer PFS than treated with the first-generation of EGFR-TKIs alone, and SFI clinically effectively retards the occurrence of first-generation EGFR-TKIs resistance.
DOI:
https://doi.org/10.1007/s00432-022-04297-3
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Radiotherapy with continued EGFR-TKIs for oligoprogressive disease in EGFR-mutated non-small cell lung cancer: A real-world study

Published date:
06/05/2022
Excerpt:
...we evaluated the efficacy of radiotherapy and continuation of TKIs in patients with advanced NSCLC with oligoprogression after EGFR-TKIs....Patients with EGFR exon 19 deletion had significantly better mPFS2 and mOS than those with EGFR exon 21 L858R mutation (mPFS2: HR = 2.755, p = 0.024; mOS: HR = 7.814, p = 0.012)
DOI:
https://doi.org/10.1002/cam4.4894
Evidence Level:
Sensitive: C3 – Early Trials
Title:

The efficacy of EGFR-tyrosine kinase inhibitor in non-small cell lung cancer patients with synchronous brain metastasis: a real-world study

Published date:
02/16/2022
Excerpt:
Patients with EGFR exon 19 deletion had a significantly longer median OS than those with other mutations including L858R (23 months vs. 17 months)….This study suggests that EGFR-TKI may result in a favorable outcome in NSCLC patients with synchronous BM, especially in deletion 19 mutant, regardless of the extent of BM lesions or local Tx modalities.
DOI:
10.3904/kjim.2021.315
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Front-Line Therapy in EGFR Exon 19 Deletion and 21 Leu858Arg Mutations in Advanced Non-Small Cell Lung Cancer: A Network Meta-Analysis

Published date:
12/13/2021
Excerpt:
This study aimed to compare the efficacy of different first-line strategies based on different EGFR mutation types (19 deletion and 21 Leu858Arg mutations)....SoC + chemotherapy provided the best overall survival benefit for the overall population and patients with 19del, with the cumulative probabilities of 57.85% and 33.51%, respectively.
Secondary therapy:
Chemotherapy
DOI:
10.1155/2021/9311875
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Real-world characteristics and outcomes of advanced non-small-cell lung cancer patients with EGFR exon 19 deletions or exon 21 mutations

Published date:
04/19/2021
Excerpt:
With EGFR-tyrosine kinase inhibitor monotherapy, unadjusted rwPFS for ex19del mutations was longer than for Leu858Arg mutations (HR: 1.62 [95% CI: 1.03-2.56]; p = 0.036). 
DOI:
10.2217/fon-2021-0218
Evidence Level:
Sensitive: C3 – Early Trials
Title:

P84.22 - Outcomes of TKI Treatment in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Real-World Study in Argentina

Published date:
01/12/2021
Excerpt:
Advanced NSCLC patients harboring uncommon (other than L858R and exon 19 deletion) EGFR mutations at baseline tissue biopsy were selected...three patients harboring concurrent de-novo resistant T790M and a common sensitive EGFR mutation (L858R or exon 19del) achieved partial response using first and second-generation EGFR-TKIs.
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Progastrin-Releasing Peptide Precursor and Neuron-Specific Enolase Predict the Efficacy of First-Line Treatment with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors Among Non-Small-Cell Lung Cancer Patients Harboring EGFR Mutations

Published date:
01/05/2021
Excerpt:
Exon 19 deletion (19-del) in EGFR, negative neuron-specific enolase (NSE), negative pro-gastrin-releasing peptide precursor (ProGRP) value, and "never smoking" status were significantly associated with improved PFS (P=0.007, P=0.001, P<0.001, and P<0.001, respectively). 
DOI:
10.2147/CMAR.S285121
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

2185 Real-World Analysis of Clinical Characters, Prognosis, And Recurrence Pattern: A Retrospective Multicenter Study of 429 Patients with Epidermal Growth Factor Receptor (EGFR) Mutant Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)

Published date:
11/01/2020
Excerpt:
A total of 429 patients met selection criteria were included in the study, among whom 209(48.7%)patients had exon 19 deletion, 165(38.5%)had L858R exon...In multivariable analysis, use of EGFR-TKIs (yes v not: HR = 0.56, 95%CI 0.43-0.74, P<0.001) and stage (IIIA v IIIB: HR = 0.67, 95% CI 0.51-0.87, P=0.003) were independently associated with PFS; and age was independently associated with OS...By multivariable analysis, EGFR-TKIs independently increased the DMFS (yes v not: HR 0.51,95%CI 0.37-0.70, P<0.001)....
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

Tyrosine Kinase Inhibitors as a Treatment of Symptomatic CNS Metastases in Oncogene-Driven NSCLC

Published date:
09/03/2020
Excerpt:
In conclusion, upfront use of next-generation EGFR TKIs and ALK TKIs in patients with EGFR-mutant and ALK-rearranged NSCLC with brain metastases is of value in multifocal, large-volume, and symptomatic intracranial tumors; their use in patients with symptomatic CNS metastases is associated with reasonable intracranial activity and symptomatic improvement.
DOI:
10.1155/2020/1980891
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

The predictive values of mutation patterns, concurrent mutations and efficacy of different generations of EGFR-TKIs in advanced non-small cell lung cancer harboring non-resistant uncommon EGFR mutations.

Published date:
05/29/2020
Excerpt:
...group1 patients harboring EGFR uncommon mutation in combination with EGFR 19 del/L858R; group 2 patients harboring single or complex EGFR uncommon mutations. Our analyses revealed that the median PFS (mPFS) of group 1 was significantly longer than those in groups 2 (14.65months vs 8.05 months; P = 0.004)....analysis revealed that patients receiving 2nd generation TKI (p = 0.006, HR:0.277,95%CI:0.112-0.688) and coexist with 19del/L858R (p < 0.001, HR: 0.148,95% CI:0.065-0.333) were independently associated with favorable PFS; while concurrent TP53 mutation was independently associated with worse PFS (p = 0.008, HR: 2.530,95% CI:1.270-5.042)....EGFR mutations in combination with 19del/L858R were associated with favorable PFS. The presence of concurrent tumor-suppressor genes mutations especially TP53 is associated with worse prognosis. Patients treated with 2nd generation EGFR-TKI showed a longer PFS...
DOI:
10.1200/JCO.2020.38.15_suppl.e21612
Evidence Level:
Sensitive: C3 – Early Trials
Title:

The Clinical Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Brain Metastases from Non–Small Cell Lung Cancer-Harboring EGFR Mutations

Published date:
02/20/2020
Excerpt:
Among the 730 NSCLC patients with BM, 133 were found to have EGFR mutations, including 24.3% (33) with exon 19 deletions and 24.3% (33) with exon 21-point mutation (L858R). One patient had both exon 19 and exon 21-point mutations...Of the 133 BM cases...65 had received EGFR-TKI...treatment by TKI (HR= 1.805; 95% CI: 1.277–2.552; factors = 0.001), and NLR (HR = 1.805; 95% CI: 1.277–2.552; factors =0.001) were associated with longer OS... The results showed that pretreatment and treatment factors including age below 65, nonsmoker, high KPS, lower number of brain lesions, absence of extracranial metastases, and being treated with WBRT or EGFR-TKI were associated with a longer overall survival...
DOI:
https://doi.org/10.2147/CMAR.S250688
Evidence Level:
Sensitive: C3 – Early Trials
New
Title:

EGFR mutation types and abundance were associated with the overall survival of advanced lung adenocarcinoma patients receiving first-line tyrosine kinase inhibitors

Excerpt:
All patients involved in the present study had sensitive EGFR mutations [either exon 19 deletion (DEL) or exon 21 L858R] and treated by EGFR-TKIs....Overall survival (OS) was significantly longer in patients with 19DEL mutation (20.9 months, 95% CI: 17.7-24.1 months versus 17.0 months, 95% CI: 14.4-19.6 months in patients with L858R; P=0.008)...
DOI:
10.21037/jtd-22-755