Abstract
Prevalence of STK11, KEAP1, and KRAS mutations/co-mutations and associated clinical outcomes for patients newly diagnosed with metastatic non-small cell lung cancer.
Author
person
Firas Dabbous
Evidera, Bethesda, MD
info_outline
Firas Dabbous, Ching-Yu Wang, Daniel Simmons, Samuel Huse, Rami Jassim
Full text
Authors
person
Firas Dabbous
Evidera, Bethesda, MD
info_outline
Firas Dabbous, Ching-Yu Wang, Daniel Simmons, Samuel Huse, Rami Jassim
Organizations
Evidera, Bethesda, MD, AstraZeneca, Gaithersburg, MD
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
AstraZeneca Pharmaceuticals
Background:
Data on the prevalence of emerging mutations /co-mutations (e.g., STK11, KRAS, and KEAP1) and associated clinical outcomes in metastatic non-small cell lung cancer (mNSCLC) patients are lacking therefore the objective of this study is to address these gaps in the current data.
Methods:
This study used the Flatiron clinico-genomic database and included newly diagnosed patients (≥18 years old) with stage IV NSCLC and known histology/PD-L1 status. Patients enrolled in clinical trials, with positive/missing EGFR or ALK, other malignancies, mixed histology, or without structured data within 90 days of diagnosis were excluded. The prevalence of STK11, KEAP1, KRAS mutations and co-mutations for each combination were evaluated in the overall study cohort and stratified by histology and PD-L1 status ( > or ≤1%). The overall survival (OS) from the date of diagnosis with stage IV was analyzed using Kaplan-Meier methods.
Results:
Of the 17,020 patients with NSCLC, 964 met the selection criteria and were included in the study. The prevalence of STK11, KEAP1, and KRAS is 18%, 15%, and 35%, respectively. With the exception of KRAS, the prevalence of all selected mutations and the co-mutations is higher in patients with PD-L1 negative and non-squamous NSCLC. The prevalence of KRAS is higher in patients with PD-L1 positive and non-squamous NSCLC (Table). The median OS was 10.1 months (95% CI, 8.6, 11.2) for the overall population, and 6.6 (5.7-8.3), 7.1 (5.8-8.8) and 9.9 (7.6-11.9) months in patients with STK11, KEAP1, and KRAS mutations, respectively. The median OS in patients with co-mutations ranges from 6.1 to 6.7 months.
Conclusions:
STK11, KEAP1, and KRAS mutations and co-mutations are common in mNSCLC patients. Current treatments, particularly in STK11, KEAP1, and co-mutation patients, are associated with poor OS. To address these harder to treat subgroups new treatment options or clinical trials should be considered.
Prevalence of mutation/co-mutations and overall survival from diagnosis stratified by PD-L1 status and histology.
Histology
PD-L1
Analysis Type
N
STK11
KEAP1
KRAS
KRAS & STK11
KRAS & KEAP1
STK11 & KEAP1
KRAS & STK11 & KEAP
Both
Both
OS (mutant vs wildtype)
964
6.6 vs. 11.1
7.1 vs 10.7
9.9 vs 10.3*
6.7 vs 10.8
6.4 vs 10.6
6.4 vs 11.3
6.1 vs 11.1
Prevalence
†
964
175 (18%)
141 (15%)
339 (35%)
95 (10%)
63 (7%)
67 (7%)
38 (4%)
Squamous
Positive
(> 1%)
Prevalence
†
164
5 (3%)
13 (8%)
21 (13%)
0 (0%)
4 (2%)
3 (2%)
0 (0%)
Squamous
Negative
(≤1%)
Prevalence
†
75
1 (1%)
5 (7%)
4 (5%)
0 (0%)
1 (1%)
1 (1%)
0 (0%)
Non-squamous
Positive
( > 1%)
Prevalence
†
498
94 (19%)
57 (11%)
236 (47%)
54 (11%)
29 (6%)
30 (6%)
19 (4%)
Non-squamous
Negative
(≤1%)
Prevalence
†
227
75 (33%)
66 (29%)
78 (34%)
41 (18%)
29 (13%)
33 (15%)
19 (8%)
OS= overall survival in months;
†
Prevalence is calculated among patients tested for each biomarker; *not statistically significant.
4 organizations
3 drugs
3 targets
Organization
Evidera, IncOrganization
Bethesda, MDOrganization
AstraZenecaOrganization
Gaithersburg, MDDrug
STK11Drug
KEAP1Drug
KRASTarget
KRAS G12CTarget
KEAP1Target
STK11