Tanios Bekaii-Saab, MD
There has been a significant evolution in the care of patients with metastatic colorectal cancer over the past 20 years. It’s been amazing. When I finished my fellowship around 2002, we had a few drugs—5-FU (5-fluorouracil) was our only option and irinotecan (Camptosar) was just approved. The average survival for patients was—with a stretch—about 11-12 months. Irinotecan pushed it a little bit. It was given with fluorouracil/leucovorin as a bolus, and it was tough for most patients. Then came oxaliplatin (Eloxatin), which added 1 cytotoxic option, and then capecitabine (Xeloda), an alternative option for a fluoropyrimidine. Following all this, it was essentially the era of biologics.
After 2004, we saw the introduction of bevacizumab (Avastin) and then cetuximab (Erbitux), panitumumab (Vectibix), and a number of other monoclonal antibodies that essentially target VEGF very similarly, but not the same. We started moving that needle from 1-year to 2-year survival, which is pretty amazing, if you think about the timeline of change. We were shifting the whole curve positively.
With EGFR inhibitors, the story started a little bit different. We started using them mostly without selecting for a gene but selecting for expression of EGFR, which did not make sense since this is an inducible protein that we measure by immunohistochemistry. Shortly after this, we learned that EGFR expression does not really matter, and in time we learned that the KRAS
gene, if mutated, will exclude those patients from receiving EGFR inhibitor therapy given the lack of benefit.
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