BACKGROUND: Evidence for TP53 mutations as biomarker in colorectal cancer (CRC) is conflicting. METHODS: We assessed TP53 mutations in 51 patients with advanced CRC enrolled into a phase II, randomised trial of first-line tegafur-uracil (UFT)/leucovorin (LV) plus irinotecan (n = 23) versus UFT/LV plus oxaliplatin (n = 28). RESULTS: Non-functional TP53 mutations were found in 35% of patients. The response rate was not significantly different according to TP53 status. Progression-free and overall survival were longer in patients with TP53 mutations compared to those with wild-type TP53 (9 vs. 6.5 months, p = 0.0504, and 39.2 vs. 19.6 months, p = 0.0055, respectively). On multivariable analysis, TP53 mutation was independently associated with a decreased risk of death (hazard ratio 0.329, 95% CI 0.159-0.679; p = 0.0026). Treatment arm did not interact with TP53 in influencing outcomes. CONCLUSION: TP53 was not predictive of benefit from first-line irinotecan- or oxaliplatin-based chemotherapy. TP53 mutations may possibly be associated with a more indolent course of CRC after the diagnosis of metastatic disease.
RCT Entities:
BACKGROUND: Evidence for TP53 mutations as biomarker in colorectal cancer (CRC) is conflicting. METHODS: We assessed TP53 mutations in 51 patients with advanced CRC enrolled into a phase II, randomised trial of first-line tegafur-uracil (UFT)/leucovorin (LV) plus irinotecan (n = 23) versus UFT/LV plus oxaliplatin (n = 28). RESULTS: Non-functional TP53 mutations were found in 35% of patients. The response rate was not significantly different according to TP53 status. Progression-free and overall survival were longer in patients with TP53 mutations compared to those with wild-type TP53 (9 vs. 6.5 months, p = 0.0504, and 39.2 vs. 19.6 months, p = 0.0055, respectively). On multivariable analysis, TP53 mutation was independently associated with a decreased risk of death (hazard ratio 0.329, 95% CI 0.159-0.679; p = 0.0026). Treatment arm did not interact with TP53 in influencing outcomes. CONCLUSION:TP53 was not predictive of benefit from first-line irinotecan- or oxaliplatin-based chemotherapy. TP53 mutations may possibly be associated with a more indolent course of CRC after the diagnosis of metastatic disease.
Authors: Romina Briffa; Inhwa Um; Dana Faratian; Ying Zhou; Arran K Turnbull; Simon P Langdon; David J Harrison Journal: PLoS One Date: 2015-12-17 Impact factor: 3.240