4234 - Correlation between p53 expression and clinical outcome in RAS/BRAF wild type metastatic colorectal cancer patients receiving later-line irinotecan-cetuximab

Background

Preclinical and clinical data support that p53 might modulate the EGFR activity and as a consequence it might influence response/resistance to anti-EGFR monoclonal antibodies. However, the association between p53 status and clinical outcome has not been clarified yet. In our study we evaluated the role of p53 expression in RAS/BRAF wild type (WT) metastatic colorectal (mCRC) patients (pts) receiving irinotecan-cetuximab by using a validation cohort.

Methods

p53 immunohistochemical expression was retrospectively analysed in tumour samples of RAS/BRAF WT mCRC pts treated with second-third line irinotecan-cetuximab. Our aim was to evaluate the correlation between p53 expression and OS, PFS and RR. Statistical analysis was performed with the MedCalc package. Survival distribution was assessed by the Kaplan-Meyer method and comparison of survival curves was performed with log-rank test.

Results

Globally 120 RAS/BRAF WT mCRC pts were included in our analysis, 88 in the exploratory cohort and 32 in the validation cohort. 36/88 and 14/32 pts had p53 normal expression, whereas 52/88 and 18/32 showed p53 overexpression. In the exploratory cohort, RR was 61.1% in pts with p53 normal expression versus (vs) 3.8% in pts overexpressing p53 (p < 0.0001); median OS (mOS) was 18 months in pts with normal p53 (95% CI 17-20) vs 8 months (95% CI 5.9-9; p < 0.0001) and median PFS (mPFS) was 8 months in pts with p53 normal status (95% CI 6.98-8.10) vs 3 months in pts with abnormal p53 (95% CI 2.90-3.63; p < 0.0001). These results were confirmed in the validation cohort: RR was 56.2% in pts with normal p53 and 43.7% in pts with abnormal p53 (p = 0.4830); mOS was 30.1 months in pts with p53 normal status (95% CI 22.42-53.31) vs 13.4 months in pts with p53 overexpression (95% CI 12.04-24.84; p = 0.03) and mPFS was 9.8 months in pts with normal p53 (95% CI 7.51-12.55) vs 7.9 months in pts with abnormal p53 (95% CI 5.32-8.21; p = 0.02).

Conclusions

In our study p53 normal expression was associated with better outcome in RAS/BRAF WT mCRC pts receiving irinotecan-cetuximab, as confirmed by the validation cohort. Further prospective studies are needed to validate the role of p53 in these pts and to investigate its cross-talk with EGFR.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Mario Scartozzi.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.