I am on my flight back from ASCO, the annual meeting of the American Society of Clinical Oncology in Orlando, where over 20,000 oncologists from around the world discuss the newest data in clinical and translational research. This year’s theme was personalized oncology care.
Last year we made a significant step forward in personalized oncology with the identification of a mutation in KRAS which is found in about 40 percent of colon cancers. This genetic switch predicts efficacy of drugs such as Erbitux and Vectibix. Since then the European Regulatory Agency EMEA approved KRAS testing in first-line metastatic colorectal cancer treatment, and since last Monday my colleagues in Europe including England can use Erbitux in wild-type KRAS tumors for first-line treatment t which we in the USA can not do.
The data have been submitted to FDA for review to be able to use Erbitux or Vectibix in first line treatment, and we expect a decision in the next couple of months.
More and more American physicians test for KRAS mutations, but still mainly when we consider starting Erbitux or Vectibix. Increasingly in the US we are beginning to test with the diagnosis of metastatic colon cancer because the planning of treatment strategies may significantly change.
This year’s meeting asked the question: Do we have new information on additional markers?
There was promising data on PI3K mutations and BRAF mutations as well as on PTEN loss and expression of the EGFR ligands. It seems that PI3K and BRAF mutations may be not so clear as the KRAS mutation story. Studies presented at ASCO showed that the data are not consistent indicating that testing for these markers should not be done routinely yet.
PTEN loss is complicated and not easily clinically feasible since you need tissue from the metastatic site and no one likes to biopsy liver or lung lesions for a molecular test. The concordance of PTEN loss is not great when compared between primary and metastic site. This is because the method of PTEN inactivation is not a mutation but methylation which is dependent on the tumor’s environment which obviously is different in the primary tumor and liver or lungs mets.
The most promising is the EGFR ligand expression. Additional data suggested that high levels increase the probability of response to EGFR inhibitors. The problem is methodology and how to determine the cut off level. In other words, what is high and what is low.