1308P - Molecular and clinical characteristics of patients with non-small cell lung cancer (NSCLC) harboring KRAS Q61 mutations

Background

KRAS Q61 mutations represent a heterogeneous subgroup of KRAS mutations. However, the prognostic value and the outcome of different treatment options remain unclear. Here, we present a real-word data analysis of KRAS Q61X mutated patients (pts) with NSCLC to further characterize molecular and clinical characteristics of this subgroup.

Methods

We queried our national Network Genomic Medicine (nNGM) database for NSCLC pts harboring KRAS Q61X mutations that were tested at our cancer center and linked clinical records. The mutational status was determined by next-generation sequencing (NGS) and PD-L1 status was analyzed by immunohistochemistry (IHC).

Results

We evaluated 365 pts that were diagnosed between 2011 and 2023 of which 18 (4.9%) presented with UICC stage I, 8 (2.2%) with stage II, 41 (11.2%) with stage III and 232 (63.6%) with stage IV. The predominant histologic subtype was adenocarcinoma (n=343, 94.0%) and the predominant mutational subtype was Q61H (n=270, 74.0%) and Q61L (n=76, 20.8%), followed by rare subtypes (Q61K=Q61R>Q61E>Q61P). The gender distribution showed no significant difference between male (n=188, 51.5%) and female (n=177, 48.5%) pts. Median age at diagnosis was 66 years (range: 38 – 89). The majority of the cohort were current or former smokers (n=268, 73.4%) with a mean of 39 pack-years and only 19 pts (5.2%) were never smokers. Common co-alterations (≥5%) among the whole cohort were TP53 mutations (n=127, 34.8%) and KEAP1 mutations (n=34, 9.3%) and among Q61H TP53 (31.9%) and KEAP1 (11.5%) and among Q61L TP53 (38.2%) and BRAF (5.3%) mutations. PD-L1 status was positive in 143 pts (59.8%) with 63 pts showing a TPS score ≥50% and negative in 96 pts (40.1%). Preliminary median overall survival (mOS) in metastatic disease was 292 days (95% CI: 194 – 390).

Conclusions

The cohort is characterized by smoking, a relatively low frequency of co-occurring mutations and a relatively short overall survival. We will further analyze the cohort regarding the impact of different treatment regimens.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

L.V. Ruge: Non-Financial Interests, Personal, Non remunerated activity, Travel expenses for participation of a congress: Amgen, Janssen. F. John: Non-Financial Interests, Personal, Non remunerated activity: Merck; Financial Interests, Personal and Institutional, Funding: AstraZeneca. H. Scharpenseel: Non-Financial Interests, Personal, Non remunerated activity, Travel expenses for participation of a congress: Janssen. R.N. Fischer: Financial Interests, Personal and Institutional, Sponsor/Funding: BMS. R. Büttner: Financial Interests, Personal, Expert Testimony: MSD; Financial Interests, Personal, Leadership Role: Gnothis Inc., Timer Therapeutics Inc. L. Nogova: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Roche, Janssen, Pfizer, Bayer, AstraZeneca; Financial Interests, Personal and Institutional, Funding: Pfizer, BMS, Novartis, MSD, Janssen, Dracen. All other authors have declared no conflicts of interest.