Eric Van Cutsem, MD, PhD, Professor of Internal Medicine at the University of Leuven in Belgium, the formal discussant of the late-breaking abstract, noted there is strong rationale for studying TP53 status in relation to rectal cancer outcomes, but he felt the findings of EXPERT-C could not yet be considered practice-changing.
“TP53, a tumor-suppressor gene, has a possible role in predicting response to radiotherapy, and, based on preclinical studies, a role in modulating response to therapies targeting the epidermal growth factor receptor,” he said. “But there have been very few, very small studies evaluating the predictive role of TP53 in metastatic colorectal cancer, and they have not been conclusive.”
EXPERT-C is an “innovative and important conceptual study” conducted by expert centers. It is “well designed” and of “high quality,” he noted, “but it is not without its weaknesses.”
The small, retrospective study has a sample size that is inadequate for validating biomarkers, there was a relatively high degree of discordance for TP53 status between the biopsy and resection samples, and the use of capecitabine/oxaliplatin as a backbone for cetuximab (Erbitux) is questionable, based on the MRC COIN trial, which did not confirm a benefit for the addition of cetuximab to oxaliplatin-based chemotherapy in first-line treatment of patients with advanced colorectal cancer,1 Dr. Van Cutsem pointed out.
“Nevertheless, it is very important to evaluate the potential role of TP53 in nonmetastatic patients,” he acknowledged. “This is an interesting, hypothesis-generating study that may be the basis for further translational studies,” he said. ■
Disclosure: Dr. Van Cutsem has received research funding paid to his institution by Merck Serono.
1. Maughan TS, Adams RA, Smith CG, et al: Results of the randomized phase 3 MRC COIN trial. Lancet 377:2103-2114, 2011.