Found 1 Presentation For Request "1809P"

Tumour biology and pathology

1809P - Evaluation of KRAS mutation subtype on survival in patients with metastatic non-small cell lung cancer receiving immunotherapy

Presentation Number
1809P
Speakers
  • Carly C. Barron (Toronto, Canada)

Abstract

Background

Activating mutations in KRAS are the most common driver mutations in metastatic non-small cell lung cancer (mNSCLC). KRAS-mutant NSCLCs are heterogeneous in their biology and the response of the various KRAS alleles to immune checkpoint inhibitors (ICI) remains unclear. We sought to investigate differential outcomes to ICI among KRAS subtypes.

Methods

Patients with KRAS mt mNSCLC receiving ICI at two institutions from 2013-2021 were included. Outcomes studied were overall response rate (ORR) and median progression-free survival (mPFS). Patients with KRAS G12C mutations were compared to non-G12C.

Results

We identified 123 patients, 42 (37%) KRAS G12C and 73 (63%) non-G12C. The G12C group were older (median 67 vs 65; p=0.05) and had a greater proportion of PD-L1 high (>50%) expression (63 vs 39%, p=0.02). There were no differences in other characteristics including smoking history: (86% vs 76%; p=0.2). Most patients received ICI monotherapy (81% vs 73%). ORR was significantly higher in G12C vs. non-G12C (49% vs 25%, p=0.031). In a multivariate logistic regression, G12C (OR 2.7, p=0.04), PD-L1≥50% (OR 4.6, p=0.002), TP53 (OR 3.0, p=0.02), but not smoking (p=0.4), were independent predictors of response. mPFS was longer in the G12C vs. non-G12C group (11.7m vs. 3.8m, p=0.1). In a multivariate analysis adjusting for smoking, TP53 and line of treatment, G12C (HR 0.6, p=0.05) and PD-L1≥50% (HR 0.5, p=0.01) remained predictive of PFS. Further subdivision by KRAS subtype and PD-L1 status (Table) revealed that patients in the G12C group with high PD-L1 expression had significant benefit from ICI over other subtypes: ORR 65%, mPFS 23.5m.

mPFS by KRAS subtype and PD-L1 expression

Group ORR mPFS (months, univariate HR, p-value)
G12C, PD-L1 high (n=24) 65% 23.5 (0.2, p<0.001)
G12C, PD-L1 low (n=14) 21% 4.7 (0.7, p=0.3)
Transversion mutation, PD-L1 high (n=23) (G12R, G12V, G12A) 43% 4.9 (0.4, p=0.02)
Transversion mutation, PD-L1 low (n=25) (G12D, G12S) 16% 4.0 (0.7, p=0.3)
Transition mutation (n=20) 20% 2.6 (ref)

Conclusions

KRAS G12C mutated tumors had higher ORR and PFS than non-G12C mutations to ICI. Further research is required to understand the molecular mechanisms by which KRAS subtype modulates the immune microenvironment and response to ICI.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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