Characteristics and survival of patients with advanced cancer and p53 mutations. Oncotarget 2014 Jun 15;5(11):3871-9
Date
07/09/2014Pubmed ID
25003695Pubmed Central ID
PMC4116527DOI
10.18632/oncotarget.2004Scopus ID
2-s2.0-84903545565 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
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.
Author List
Said R, Ye Y, Hong DS, Janku F, Fu S, Naing A, Wheler JJ, Kurzrock R, Thomas C, Palmer GA, Hess KR, Aldape K, Tsimberidou AMAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Clinical Trials, Phase I as TopicFemale
Genes, p53
Humans
Male
Middle Aged
Mutation
Neoplasms
Prognosis
Survival Analysis
Survival Rate
Treatment Outcome
