Abstract 355P
Background
All RAS wild-type metastatic colorectal cancer patients do not have the same benefit from the anti-epidermal growth factor receptor (EGFR) therapies. Studies have shown that nuclear factor-kB (NF-kB), hypoxia-inducible factor-1α (HIF-1α), interleukin 8 (IL-8) and transforming growth factor β (TGF-β) may be therapeutic targets for metastatic colorectal cancers. We aimed to clarify the prognostic value of NF-κB, HIF-1α, IL-8 and TGF-β expression in patients receiving EGFR inhibitors in left sided mCRC patients.
Methods
Patients with RAS wild-type, left side mCRC treated with anti-EGFR on the first-line between September 2013 and April 2022 were included. Immunohistochemical staining for NF-κB, HIF-1α, IL-8 and TGF-β was performed from tumor tissues of 88 patients. Patients were divided into NF-κB, HIF-1α, IL-8 and TGF-β expression positive and negative group, moreover expression positive group were also divided into two group as expression intensity low and high group. The median follow-up was 25.2 months.
Results
Median progression-free survival(PFS) was 8.1 (6-10.2) months in the cetuximab group, 11.3 (8.5-14) months in the panitumumab group (p=0.09). Median overall survival (OS) was 23.9 (4.3-43.4) months in the cetuximab group, 26,9 (15.9-31.9) months in the panitumumab group (p=0.8). NF-kB expression was present in all patients. The mOS was 19.8 (11-28.6) months in NF-kB expression intensity low group and 36.5 (20.1-52.8) months in high group (p=0.03). The mOS of the HIF-1α expression negative group was significantly longer compared with expression positive group (p=0.014). There was no significant difference in IL-8 and TGF-b expression status on mOS and mPFS (for all, p>0.05). Positive expression of HIF-1α was poor prognostic for mOS in the univariate analysis (HR:2.7, 95% CI: 1.18-96.52, p=0.02) and in multivariate analysis (HR: 3.69, 95% CI: 1.41-9.6, p=0.008). High expression intensity of NF-kB was found to have a good prognostic value for mOS (HR: 0.47, 95% CI: 0.26-0.85, p=0.01).
Conclusions
High expression intensity of NF-κB and negative expression of HIF-1α could be a good prognostic marker for mOS in RAS wild type left side mCRC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Scientific Research Projects (BAP) fund.
Disclosure
All authors have declared no conflicts of interest.