SAN FRANCISCO – None of the common KRAS mutant alleles seen in metastatic colorectal cancer reliably predict benefit from panitumumab, new data show, suggesting that this agent should continue to be used only in patients with KRAS wild-type tumors.
Investigators led by Dr. Marc Peeters of Antwerp University Hospital in Edegem, Belgium, analyzed data from a trio of phase III randomized trials of panitumumab (Vectibix), an antibody to epidermal growth factor receptor (EGFR), in more than 1,400 patients.
Dr. Marc Peeters
Main results showed that there was no consistent difference in benefit across trials in terms of progression-free and overall survival for patients having the most common codon 12 and 13 KRAS mutant alleles, he reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
In a pooled analysis, a significant association was seen only for the G12A mutant allele, whereby patients having this allele had poorer overall survival when panitumumab was added to their treatment.
"The take-home message based on this study: Patients with metastatic colorectal cancer harboring any of the most common codon 12 or 13 mutant KRAS alleles are unlikely to benefit from panitumumab treatment. Today, only metastatic colorectal cancer patients with wild-type KRAS tumors should be treated with EGFR antibodies," Dr. Peeters asserted.
Previous research (JAMA 2010;304:1812-20), has suggested that patients with the G13D KRAS mutant allele might still benefit from cetuximab, another antibody to EGFR, an attendee noted. Therefore, is it possible that there is some biological difference between panitumumab and cetuximab (Erbitux) when it comes to this allele?
"The results I presented here were based on a large data set treated with panitumumab and a very homogeneous population, which really shows ... that there is no benefit of treating patients with G13D with panitumumab," Dr. Peeters replied. "If you compare the results ... of data with cetuximab, this population is more heterogeneous than we studied in the panitumumab group.
"So it’s very difficult to draw final conclusions ... on standard of care of patients. My advice is still that patients with mutant tumors probably in general don’t benefit from treatment with EGFR antibodies, although from a scientific point of view, the discussion is still open and we have to search further [to see] if there is really a difference between the antibodies based on the results obtained in the literature," he added.
"And one of the studies that could answer this question is a head-to-head study that we are performing, where cetuximab is compared with panitumumab, and this might give us a better idea what is really the difference between the antibodies."