38P - The immunotherapy role in patients (pt) with KRAS mutated metastatic non-small cell lung cancer (NSCLC): Differences between KRAS G12C and non-G12C

Background

Approximately 20% of lung adenocarcinomas harbor KRAS mutations (mut), an oncogene that drives tumorigenesis and has the ability to alter the tumor immune microenvironment. The most common mut is KRAS G12C, representing ∼40%, which has been related with tobacco exposure. Despite the immune-related nature of KRAS driven tumors, the efficacy of immunotherapy (IT) according to KRAS mut type has not been well elucidated. The objective of this study is to describe a cohort of pt with KRAS-mut NSCLC and evaluate the clinical outcomes with immunotherapy according to KRAS mut type.

Methods

A retrospective cohort of KRAS-mut NSCLC pt treated at Catalan Institute of Oncology (Badalona) between 2013-2020 were included in this study. KRAS status was determined by using the cobas® KRAS mut test, a real-time PCR test designed for the identification of mut in codons 12, 13 and 61; and NGS (Oncomine Solid) in the recent cases (2020). PD-L1 status was determined by immunohistochemistry assay (VENTANA PD-L1 SP263). PD-L1 status in tumor cells was categorized as: negative <1%, low 1-49% and high 50-100%. Chi-square test for categorical variables and Kaplan Meier method for survival analysis were performed.

Results

Of the 120 pt included: 75% were male, median age at diagnosis was 63. 96% were current or former smokers. At diagnosis, 74% of pt had stage IV lung adenocarcinoma. KRAS status was determined in 107 pt: 46% harbored KRAS G12C and 54% KRAS nonG12C. High PD-L1 was detected in 37% of cases, predominantly in KRAS G12C vs nonG12C (56% vs 44% p=0.2). A total of 65 pt (54%) were treated with IT for advanced disease; 42% in 1^st line, 46% in 2^nd and 12% in 3^rd. 81% received anti-PD-1, 16% anti-PD-L1 and 3% anti-CTLA-4. After median follow up of 63m, the median progression free survival (mPFS) to IT was 10.1m vs 3.3m in KRAS G12C vs nonG12C, respectively (p=0.07); the mOS was 17.9m vs 18.6m in KRAS G12C vs nonG12C (p=0.13).

Conclusions

KRAS mut represent an heterogenous group of NSCLC. Although no statistically significant, pt with KRAS G12C mut tended to present better mPFS to IT compared to nonG12C pt, with no impact on OS. A deeper understanding of biology in KRAS mutant tumors in the era of molecular testing and precision medicine is essential.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.