Background

Non-small cell lung cancer (NSCLC) can harbor different KRAS mutations. Although targeted therapy is available for KRAS G12C-mutant NSCLC, immune checkpoint inhibitors (ICIs) are still the first line treatment (tx) for these patients (pts). Here we aimed to assess the outcomes on ICIs for KRAS G12C compared to KRAS non-G12C-mutant pts.

Methods

This is an observational, retrospective, multicenter study in pts with KRAS-mutant NSCLC treated with ICIs (monotherapy or combination) between January 2017 and January 2023. Targeted sequencing was performed in most cases. Clinicopathological and molecular data were collected. We evaluated pts characteristics, tx response and survival outcomes from the beginning of ICIs in KRAS G12C vs non-G12C tumors.

Results

A total of 169 pts were included. NGS was performed in 105 pts, STK11 and TP53 were the most frequent co-mutated genes present in 4.4%/15% G12C/non-G12C (p=0.110) and 20%/35% G12C/non-G12C (p=0.143), respectively. There were no differences in median progression free survival (PFS) between G12C/non-G12C (8.8 vs 7.1 months(m) respectively p=0.727). In the multivariate analysis, PD-L1 negative tumors and ECOG ≥1 remained independently associated with worse PFS (p=0.010 and p= 0.002 respectively). Regarding overall survival (OS), harboring a G12C mutation was associated with a better OS compared with non-G12C tumors (mOS 16.2m vs 10.4m p=0.033), conversely PD-L1 negative tumors and basal ECOG of ≥1 was associated with worse OS (p= 0.002 and p<0.001 respectively).

Table: 1408P

Patient’s characteristics

Conclusions

Our work shows that patients with KRAS non-G12C tumors are more frequently PD-L1 negative and harbor a higher proportion of STK11 co-mutations conditioning a worse OS on immunotherapy treatment. Innovative therapeutic strategies need to be investigated for these patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L. Masfarre Pinto: Other, Personal, Other, Travel Support: Kyowa Kirin. N. Castro Unanua: Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Ownership Interest, Travel, congress registration: Merck, Roche; Financial Interests, Personal, Ownership Interest, Grant support: Expert Degree in Immuno-Oncology: Bristol Myers Squibb; Financial Interests, Personal, Ownership Interest, Travel: Pfizer. P. Rocha: Non-Financial Interests, Personal, Other, Travel Support: AstraZeneca. B. Bellosillo Paricio: Other, Personal, Other, Grant: Thermo Fisher, Roche Diagnostics, Roche Farma, AstraZeneca; Other, Personal, Other, Consultant: Amgen, AstraZeneca, Janssen, Novartis; Other, Personal, Speaker’s Bureau: Janssen, Merck-Serono, Novartis, Qiagen, Thermo Fisher, Pfizer, Bristol Myers Squibb. H. Arasanz: Other, Personal, Advisory Board: AstraZeneca; Other, Personal and Institutional, Other, Clinical Trial Coordination: Ferrer Farma; Other, Personal, Other, accommodation/travel expenses: Takeda, MSD, Angelini Farma. E. Arriola: Financial Interests, Personal, Advisory Board: Roche, Boehringer Ingelheim, Lilly; Financial Interests, Personal, Invited Speaker: Takeda, MSD, AstraZeneca, BMS, Thermo Fisher Scientific, Guardant Health, Pfizer; Financial Interests, Personal, Other, Co-founder: Trialing Health; Financial Interests, Institutional, Research Grant: AstraZeneca. All other authors have declared no conflicts of interest.