Abstract 367P
Background
Non-small cell lung cancer (NSCLC) with KRAS mutations presents distinct challenges in treatment and prognosis. While immunotherapy has become a cornerstone in first-line management, reliable tools for monitoring therapeutic response are still lacking. This study aims to identify prognostic clinical biomarkers and demonstrate the clinical utility of monitoring KRAS mutational status in NSCLC patients undergoing first-line immunotherapy, with the goal of optimizing treatment outcomes.
Methods
A retrospective cohort of 37 patients from the Consorcio Hospital General Universitario de Valencia and diagnosed with KRASmutated NSCLC were included in this study. Blood samples from 23 of them were collected and analyzed using digital PCR (dPCR, Applied Biosystems™ QuantStudio™ Absolute Q, ThermoFisher Scientific). Patients were categorized into two groups according to the presence of at least one (poor prognosis) or none (good prognosis) of the following: i) Variant allele frequency (VAF)% > 1.97 (median VAF of shedders) at baseline ii) VAF% became detectable during follow-up iii) VAF% remains detectable.
Results
Clinical characteristics of the patients are summarized in the table. The median progression-free survival (PFS)was 8.9 months. ECOG status, PD-L1 expression LDH levels and a neutrophil-lymphocyte ratio (NLR) were significantly related with PFS (p < 0.05). At baseline, 78% patients (18/23) had detectable ctDNA, while 22% (5/23) did not. Patients in the poor prognosis group had significantly worse PFS compared to the good prognosis group (8.97 vs. 23.23 months, p=0.036).
Table 367P| Characteristics | N=37 |
| Age (median) | 61.6 (38–83) |
| Gender | |
| Male | 28 (75.7) |
| Female | 9 (24.3) |
| PD-L1 | |
| Negative | 13 (35.1) |
| 1–49% | 9 (24.3) |
| ≥50% | 11 (29.8) |
| Unknown | 4 (10.8) |
| KRAS mutation | |
| G12C | 26 (70.3) |
| G12V | 2 (5.4) |
| G12D | 2 (5.4) |
| Others | 7 (28.9) |
| First line treatment | |
| Chemo-IO | 24 (64.9) |
| Chemo | 3 (8.1) |
| IO | 9 (24.3) |
| Targeted therapy | 1 (2.7) |
Conclusions
KRAS-mutated NSCLC is a highly heterogeneous disease with variable responses to immunotherapy. These findings underscore the importance of integrating clinical characteristics and high-sensitivity techniques, such as dPCR, into clinical practice to enable early detection of molecular responses to treatment.
Funding
GIDO 2024 and CB16/12/00350
Disclosure
All authors have declared no conflicts of interest.