Abstract 4234
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.
Resources from the same session
3353 - Results of the 3rd interim analysis of C-Patrol: A non-interventional study on olaparib in German routine clinical practice
Presenter: Jalid Sehouli
Session: Poster Display session 2
Resources:
Abstract
740 - A real-world analysis of the treatment of advanced ovarian cancer with PARPIs
Presenter: Alejandra Martinez de Pinillos
Session: Poster Display session 2
Resources:
Abstract
5867 - Incidence of tumour BRCA1/2 variants in relapsed, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer
Presenter: Robert Morgan
Session: Poster Display session 2
Resources:
Abstract
2966 - Frequency of mutations in 21 hereditary breast and ovarian cancer susceptibility genes among 882 high-risk individuals
Presenter: Jihong Liu
Session: Poster Display session 2
Resources:
Abstract
1687 - BRCA testing of 1,284 Brazilian patients for hereditary breast and ovarian cancer in a routine diagnostic setting
Presenter: Fernanda Milanezi
Session: Poster Display session 2
Resources:
Abstract
3162 - A multi-center integrative study on cancer predisposition genes in Chinese patients with epithelial ovarian carcinoma
Presenter: Changbin Zhu
Session: Poster Display session 2
Resources:
Abstract
5993 - Incidental Early Occult Ovarian Cancer after Risk-Reducing Salpingo-Oophorectomy in BRCA1/2 Mutation Carriers followed in a Community Public Hospital
Presenter: Begona Grana Suarez
Session: Poster Display session 2
Resources:
Abstract
5334 - Response to chemotherapy in ovarian cancer (OC) patients with or without prior breast cancer (BC), stratified by BRCA mutation (BRCAm) status
Presenter: Angela George
Session: Poster Display session 2
Resources:
Abstract
4565 - Advanced ovarian cancer: is residual disease after debulking surgery affected by genetics factors involved in angiogenesis and immunity pathways?
Presenter: Michele Bartoletti
Session: Poster Display session 2
Resources:
Abstract
3251 - Surrogate endpoint of progression-free (PFS) and overall survival (OS) for advanced ovarian cancer (AOC) patients (pts) treated with neo-adjuvant chemotherapy (NACT): Results of the CHIVA randomized phase II GINECO study
Presenter: Fabrice Lecuru
Session: Poster Display session 2
Resources:
Abstract