title: Characteristics and survival of patients with advanced cancer and p53 mutations.
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.
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Internal Medicine, Oncology Division, The University of Texas Health Sciences Center, Houston, TX.
authors.forename: Rabih
authors.initials: R
authors.lastname: Said
authors.forename: Yang
authors.initials: Y
authors.lastname: Ye
authors.forename: David S
authors.initials: DS
authors.lastname: Hong
authors.forename: Filip
authors.initials: F
authors.lastname: Janku
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: Aung
authors.initials: A
authors.lastname: Naing
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Wheler
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.forename: Christoforos
authors.initials: C
authors.lastname: Thomas
authors.forename: Gary A
authors.initials: GA
authors.lastname: Palmer
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.forename: Kenneth
authors.initials: K
authors.lastname: Aldape
authors.affiliation: Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Apostolia M
authors.initials: AM
authors.lastname: Tsimberidou
mesh_terms: D017321:Clinical Trials, Phase I as Topic; D005260:Female; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy; D011379:Prognosis; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome