p53 Mutation in Advanced Solid Tumors Linked to Aggressive Course


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Mutations in the tumor-suppressor protein p53, among the most common mutations in cancers, affect apoptosis, genomic stability, and angiogenesis. To determine the effect of p53 mutation on clinical characteristics and disease and treatment outcomes, Rabih Said, MD, MPH, and colleagues from The University of Texas MD Anderson Cancer Center in Houston retrospectively reviewed data from 121 consecutive patients with solid tumors referred to the Center’s Clinical Center for Targeted Therapy phase I program who had been tested for p53 mutations.1

Mutation Associated with Liver Metastasis, PTEN Loss

Of the 121 patients, 65 (54%) had mutant p53. The presence of p53 mutations was not associated with sex or race. Metastasis to the liver occurred in 44 patients (68%) with mutant p53, compared with 26 patients (46%) with wild-type p53 (P = .0264); there was no difference in proportions of patients with metastasis to bone, lungs, brain, soft tissue, or adrenal glands according to mutant vs wild-type p53. The p53 mutation also showed a trend toward an association with loss of function of the tumor-suppressor gene PTEN, which occurred in 30% of patients with mutant p53, compared with 11% of patients with wild-type p53 (P = .053).

Bevacizumab Improves Survival in Mutant p53 Disease

Among patients with p53 mutations, the best median progression-free survival prior to phase I trial entry was 10.97 months (range, 0.85–29.04 months) when the treatment regimen included bevacizumab (Avastin) and 4.37 months (range, 0.92–14.98 months) when the treatment did not include bevacizumab (P = .0046). Among patients with wild-type p53, there was no significant difference in progression-free survival between patients receiving bevacizumab-containing regimens and patients not receiving such regimens.

Median overall survival from diagnosis was 7.7 years in patients with mutant p53 vs 11.8 years for those with wild-type p53 disease (P = .03). Univariate analysis of overall survival from time of diagnosis showed that mutant p53, Hispanic race (vs Caucasian), and shorter time from diagnosis to metastasis were associated with worse prognosis.

As summarized by the investigators, “Tumors with p53 mutation have a more aggressive clinical behavior, metastasize more to the liver, and may have a higher rate of PTEN loss compared to tumors with wild-type p53…. In addition, antiangiogenic agents may be of therapeutic value in p53-mutated patients.” ■

Disclosure: Dr. Said reported no potential conflicts of interest.

Reference

1. Said R, Hong DS, Wheler JJ, et al: p53 mutations in advanced cancers: Clinical characteristics and outcomes in a phase I setting. 2012 ASCO Annual Meeting. Abstract 10607. Presented June 4, 2012.



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