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Association details:
Biomarker:EGFR L861Q
Cancer:Non Small Cell Lung Cancer
Drug:gefitinib (EGFR inhibitor)
Direction:Sensitive
Evidence:
Evidence Level:
Sensitive: A2 - Guideline
Source:
Published date:
03/16/2022
Excerpt:
The NCCN NSCLC Panel has preference stratified the systemic therapy regimens and decided that afatinib or osimertinib are preferred options for patients with metastatic NSCLC and EGFR L861Q, G719X, and S768I mutation; other recommended options include erlotinib, gefitinib, dacomitinib.
Evidence Level:
Sensitive: B - Late Trials
New
Title:

Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR

Excerpt:
First-line gefitinib for patients with advanced non–small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy.
Secondary therapy:
paclitaxel + carboplatin
DOI:
10.1056/NEJMoa0909530
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Dynamic Changes of Circulating Tumor DNA in Late Stage NSCLC Patients

Excerpt:
...- Activating EGFR mutations (G719A/C/S; Exon 19 insertion/deletion; L858R; L861Q)...
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Selumetinib in Combination With Gefitinib in NSCLC Patients

Excerpt:
...A tumor harboring an EGFR mutation known to be associated with drug sensitivity (ie, exon 19 deletion , L858R, L861Q, G719X etc.)....
Less C2 evidence
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

145P-UpSwinG: real-world, non-interventional cohort study on TKI activity in patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC with uncommon mutations

Published date:
03/17/2021
Excerpt:
Uncommon mutation categories were: major uncommon (G719X, L861Q, S768I; 73%); compound (35%); ex20ins (12%); T790M (7%); other (9%). Most pts (n = 226; 92%) were treated in 1st-line with an EGFR TKI; 132 (54%), 70 (28%), 35 (14%) and 7 (3%) received afatinib, gefitinib, erlotinib and osimertinib....Overall median OS was 24.4 mos....ORR was 42% overall (major: 50%; compound: 49%; other: 44%; T790M: 20%; ex20ins: 17%); afatinib: 44% (DoR: 12.0 mos); 1st-gen TKIs: 44% (DoR: 11.0 mos)....Response was highest in pts with major uncommon, and/or compound mutations.
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Treatment and Outcomes of Metastatic Non-Small-Cell Lung Cancer Harboring Uncommon EGFR Mutations: Are They Different from Those with Common EGFR Mutations?

Published date:
10/07/2020
Excerpt:
...EGFR mutation-positive NSCLC received first-generation (1G, gefitinib or erlotinib) or 2G EGFR-TKI (afatinib) as the first-line (1L) systemic therapy....The objective response rate (ORR) for the 1L EGFR-TKI was 63.3%. The median progression-free survivals (PFSs) were 8.6 months (95% CI: 3.8-13.5), 11.7 months (95% CI: 6.6-16.7), 7.7 months (95% CI: 4.9-17.4), and 5.0 months (95% CI: 3.7-6.1) for major uncommon EGFR mutation (G719X, L861Q), compound mutation with major EGFR mutation (Del 19 or EGFR exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively.
DOI:
10.3390/biology9100326
Evidence Level:
Sensitive: C3 – Early Trials
Title:

502P - Epidermal growth factor receptor tyrosine kinase inhibitor treatment response in advanced non-small cell lung cancer with uncommon mutations: A multicenter observational study

Published date:
11/23/2019
Excerpt:
Moreover, the PFS of patients with the G719X mutation (n = 12, median PFS: 32.9 months) was longer than that of patients with the L861Q mutation (n = 4, median PFS: 11.1) and compound mutations (n = 4, median PFS 7.3 months)….First and second generation EGFR-TKIs are effective treatments for patients with NSCLC with uncommon mutations. Notably, a greater favorable response was observed in patients with G719X mutations than those with L861Q and compound mutations.
Evidence Level:
Sensitive: C3 – Early Trials
New
Source:
Title:

Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non–Small-Cell Lung Cancer to Gefitinib

Excerpt:
A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene, which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib....Figure 2. Mutations in the EGFR Gene in Gefitinib-Responsive Tumors...
DOI:
10.1056/NEJMoa040938
Evidence Level:
Sensitive: C3 – Early Trials
New
Title:

Impact of Epidermal Growth Factor Receptor and KRAS Mutations on Clinical Outcomes in Previously Untreated Non–Small Cell Lung Cancer Patients: Results of an Online Tumor Registry of Clinical Trials

Excerpt:
Some of these include mutations known to be associated with sensitivity (L861Q) or resistance (exon 20 insertions) to EGFR-TKI. Other mutations or combinations of mutations, 
DOI:
10.1158/1078-0432.CCR-09-0888
Evidence Level:
Sensitive: C3 – Early Trials
New
Title:

Effectiveness of Tyrosine Kinase Inhibitors in Japanese Patients with Non-small Cell Lung Cancer Harboring Minor Epidermal Growth Factor Receptor Mutations: Results from a Multicenter Retrospective Study (HANSHIN Oncology Group 0212)

Excerpt:
Out of 56 patients with minor mutations of the EGFR gene, 44 were treated with either gefitinib or erlotinib. Mutation sites were G719X in exon 18 (n=35), L861Q in exon 21 (n=11), and G874S in exon 21 (n=1). Three patients had both the G719S and the L861Q mutation....Treatment with first-generation EGFR-TKIs, in particular erlotinib, may be considered a first- or second-line option for patients with NSCLC with minor EGFR mutations.
Evidence Level:
Sensitive: D – Preclinical
New
Source:
Title:

Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants

Excerpt:
Cell In different EGFR variant-expressing 32D cells, only cells harboring L858R, E746-A750 deletion, and G719S mutants were clearly more sensitive to gefitinib than wild-type EGFR-expressing cells. Cell expressing the L861Q mutant were also more sensitive, but to a less extent. also more sensitive, but to a less extent. 
DOI:
10.1038/sj.onc.1209159