Characteristics and survival of patients with advanced cancer and p53 mutations

// Rabih Said 1,2 , Yang Ye 1 , David S. Hong 1 , Filip Janku 1 , Siqing Fu 1 , Aung Naing 1 , Jennifer J. Wheler 1 , Razelle Kurzrock 1,3 , Christoforos Thomas 4 , Gary A. Palmer 5 , Kenneth R. Hess 6 , Kenneth Aldape 7 and Apostolia M. Tsimberidou 1 1 Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX 2 Department of Internal Medicine, Oncology Division, The University of Texas Health Sciences Center, Houston, TX 3 Center for Personalized Therapy and Clinical Trials, University of California San Diego - Moores Cancer Center, San Diego, CA 4 Department of Biology and Biochemistry, University of Houston, Houston, Texas 5 Foundation Medicine, Cambridge, MA 6 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 7 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX Correspondence: Apostolia-Maria Tsimberidou, email: // Keywords : p53 mutations, matched therapy, molecular aberrations Received : February 21, 2014 Accepted : May 23, 2014 Published : May 25, 2014 Abstract P53 mutations are associated with invasive tumors in mouse models. We assessed the p53mutations and survival in patients with advanced cancer treated in the Phase I Program. Of 691 tested patients, 273 (39.5%) had p53 mutations. Patients with p53 mutations were older (p<.0001) and had higher numbers of liver metastases (p=.005). P53 mutations were associated with higher numbers of other aberrations; PTEN (p=.0005) and HER2 ( p=.003)aberrations were more common in the p53 mutation group. No survival difference was observed between patients with p53 mutations and those with wild-type p53. In patients with wild-type p53 and other aberrations, patients treated with matched-therapy against the additional aberrations had longer survival compared to those treated with non-matched-therapy or those who received no therapy (median survival, 26.0 vs. 11.8 vs. 9.8 months, respectively; p= .0007). Results were confirmed in a multivariate analysis (p= .0002). In the p53 mutation group with additional aberrations, those who received matched-therapy against the additional aberrations had survival similar to those treated with non-matched-therapy or those who received no therapy (p=.15). In conclusion, our results demonstrated resistance to matched-targeted therapy to the other aberrations in patients with p53 mutations and emphasize the need to overcome this resistance.