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Association details:
Biomarker:EGFR L861Q
Cancer:Non Small Cell Lung Cancer
Drug:erlotinib (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: C2 – Inclusion Criteria
New
Title:

Erlotinib and Chemotherapy for Patients With Stage IB-IIIA NSCLC With EGFR Mutations (ECON)

Excerpt:
...- Patients must have lung cancer with a documented EGFR activating mutation (exon 19 deletion, L858R, L861Q)...
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

INC280 and Erlotinib Hydrochloride in Treating Patients With Non-small Cell Lung Cancer

Excerpt:
...- A tumor that harbors an EGFR mutation known to be associated with drug sensitivity (i.e. G719X, exon 19 deletion, L858R, L861Q)...
Trial ID:
More C2 evidence
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

A Multicenter Randomized Phase III Study Comparing Second-line Treatment With Chemotherapy Associated or Not to Erlotinib in NSCLC Patients With Secondary Resistance to TKI-EGFR

Excerpt:
...- Presence of one of the EGFR activating mutations in the tumor (exon 19 deletion or L858R, G719X or L861Q)...
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

A Study of LY2875358 in Participants With Non-Small Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations

Excerpt:
...- Have molecular evidence of an epidermal growth factor receptor mutation (EGFRmt) known to be associated with EGFR tyrosine kinase inhibitor (TKI) drug sensitivity (G719X, exon 19 deletion, L858R, L861Q)...
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Trial of Erlotinib and BKM120 in Patients With Advanced Non Small Cell Lung Cancer Previously Sensitive to Erlotinib

Excerpt:
...Exon 19 deletion; G719S, G719A, G719C mutations (Exon 19);or L861Q (laboratory report required at enrollment)....
Less C2 evidence
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Evaluation of Treatment Efficacy of Tyrosine Kinase Inhibitors in Rare Single EGFR Exon 21 L861Q Mutation: Single Center Experience

Published date:
07/01/2022
Excerpt:
Progression-free survival and overall survival of 30 non-small cell lung cancer patients treated with erlotinib or afatinib due to single epidermal growth factor receptor L861Q positivity were compared retrospectively....Median progression-free survival was 12.8 months in the erlotinib group and 9.3 months in the afatinib group. Median overall survival in erlotinib and afatinib groups was 77.9 months and 30.3 months, respectively....Survival times of erlotinib and afatinib treatment are similar in patients with a single epidermal growth factor receptor L861Q mutation....In patients with rare mutation exon 21 L861Q positivity, both first-generation and second-generation tyrosine kinase inhibitors should be considered.
DOI:
10.5152/TurkThoracJ.2022.21270
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:

Clinicopathologic Characteristics, Treatment Outcomes, and Acquired Resistance Patterns of Atypical EGFR Mutations and HER2 Alterations in Stage IV Non–Small-Cell Lung Cancer

Published date:
12/21/2019
Excerpt:
Among the 10 patients who received erlotinib, the ORR was 10% and the DCR was 50%. The DCR by a-EGFR mutation was as follows: G719X (2/4, 50%), L861Q (2/3, 66%), and exon 20 insertion (1/3, 33%).
DOI:
https://doi.org/10.1016/j.cllc.2019.11.008
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
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...The median PFS for all 44 patients was 6.70 months [95% confidence interval (CI)=2.06-8.66 months], with a longer median PFS for those treated with erlotinib than gefitinib (7.50 versus 5.83 months; log-rank p=0.32) (Figure 2)….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.
DOI:
35(7):3885-91
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
Source:
Title:

Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy

Excerpt:
...recent studies revealed that these rare genotypes could be targetable if appropriate TKI are selected. For example, G719X (X denotes A, S, C and so on), Del18, E709K, insertions in exon 19 (Ins19), S768I or L861Q showed moderate sensitivities to gefitinib or erlotinb with ORR of 30%–50%
Evidence Level:
Sensitive: C4 – Case Studies
Title:

Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma

Published date:
08/22/2022
Excerpt:
The first case is a 65-year-old woman (P27), initially diagnosed with a localized form of NSCLC and treated by conventional chemotherapy and radiotherapy. After developing metastasis, she tested positive for the p.L861Q mutation and had received a 1-year long erlotinib therapy. Now she is in complete remission with an OS of 40 months...
DOI:
https://doi.org/10.3390/genes13081499