The Role of p53 Expression in Patients with RAS/BRAF Wild-Type Metastatic Colorectal Cancer Receiving Irinotecan and Cetuximab as Later Line Treatment

• DOI: 10.1007/s11523-021-00816-3
• Publication Date: 2021-05-10T10:08:49Z
• Authors: Pina Ziranu; Eleonora Lai; Marta Schirripa; Marco Puzzoni; Mara Persano; Andrea Pretta; Giada Munari; Nicole Liscia; Valeria Pusceddu; Fotios Loupakis; Laura Demurtas; Michela Libertini; Stefano Mariani; Marco Migliari; Marco Dubois; Riccardo Giampieri; Giovanni Sotgiu; Angelo Paolo Dei Tos; Sara Lonardi; Alberto Zaniboni; Matteo Fassan; Mario Scartozzi
• Keywords: Adult; Male; Cetuximab; Middle Aged; Irinotecan; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Antineoplastic Combined Chemotherapy Protocols; Humans; Female; Original Research Article; Neoplasm Metastasis; Tumor Suppressor Protein p53; Colorectal Neoplasms; Aged

Preclinical and clinical data indicate that p53 expression might modulate the activity of the epidermal growth factor receptor (EGFR), influencing 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 patients with RAS/BRAF wild-type metastatic colorectal cancer (mCRC) receiving irinotecan/cetuximab in an exploratory and a validation cohort.p53 expression was analysed in patients with RAS/BRAF wild-type mCRC receiving second-line or third-line irinotecan/cetuximab. Survival distribution was assessed by the Kaplan-Meier method, while the log-rank test was used for survival comparison.Among 120 patients with RAS/BRAF wild-type mCRC included in our analysis, 52 (59%) and 19 (59%) patients showed p53 overexpression in the exploratory and validation cohort, respectively. In the exploratory cohort, low p53 expression was correlated with better median progression-free survival (hazard ratio 0.39; p < 0.0001), median overall survival (hazard ratio: 0.23; p < 0.0001) and response rate (p < 0.0001). These results were confirmed by data of the validation cohort where we observed better median progression-free survival (hazard ratio: 0.48; p = 0.0399), median overall survival (hazard ratio: 0.26; p = 0.0027) and response rate (p =0.0007) in patients with p53 normal expression mCRC.In our study, p53 overexpression was associated with anti-EGFR treatment resistance in patients with RAS/BRAF WT mCRC, as confirmed in a validation cohort. Larger studies are needed to validate the role of p53 and investigate EGFR cross-talk in these patients.