EGFR-INHIBITORS IN COLORECTAL CANCER

Hello. I am David Kerr, Professor of Cancer Medicine at the University of Oxford and past President of ESMO (European Society for Medical Oncology). Today I would like to talk about an interesting study that was presented recently in the Annals of Oncology by Alfredo Falcone and his group from northern Italy.^[1] It's a phase 2 study in which the authors selected patients with quadruple wild-type metastatic colorectal cancer for first-line treatment. They selected patients by typing them for KRAS, HRAS, NRAS, and BRAF and made absolutely certain that all of the patients they selected had wild-type disease. They were looking at the combination of a regimen that they had pioneered, the FOLFOXIRI regimen, with panitumumab. They had previously shown that FOLFOXIRI is superior to conventional FOLFIRI in a small, randomized trial.^[2] We were looking at the combination of their regimen with the anti-EGFR antibody panitumumab.

They had some interesting results. They screened 87 patients and selected 37 for entry to the trial. Of those 37 patients, 33 had objective response rates of around 90%, and toxicity patterns were pretty reasonable. The dose of the chemotherapy was modified somewhat, but there was mainly neutropenia, diarrhea, and rash associated with panitumumab. Of the patients that they treated, 16 (43%) underwent primary resection of hepatic metastases, and of those 16 patients, 13 were R0 -- the resection margins were completely free of tumor. Median duration of progression-free survival was almost 12 months.

This study caught my attention for 2 reasons. One is the complexity of the regimen. This is a phase 2 study with all of the data warnings that go with those. That fantastic response rate of 90% is utterly remarkable. There was a very high resection rate, of course, in a very highly selected patient population. The second point of interest was that we have a series of molecular discriminants being used to select what seems to be a very effective regimen. They typed the patients for 4 individual genes to ensure that they were wild-type. It feels as if colorectal cancer is catching up with lung cancer and is becoming a disease that is increasingly defined by the genotype and not by a particular clinical phenotype.

This is an interesting phase 2 study. We aim to watch that space with interest to see if they actually move forward and do the randomized trial in that highly selected patient group. The results are very promising and interesting and perhaps are a small herald of the future as to where we will see increasing compartmentalization of colorectal cancer.

As always, thanks for listening. We would be happy to take any questions. Medscapers, ahoy.