We were all convinced that when we added Erbitux and Avastin to our chemotherapy, it would work in the adjuvant setting, which means with FOLFOX for 6 months after the successful removal of colon cancer.
But it did not work. Neither Avastin nor Erbitux showed any benefit. How is that possible?
This forces us to go back to the drawing board and get smarter and learn from these experiences. What we must assume is that when you treat with these antibodies, it does not work when you only have microscopic disease.
The reason tumors recur is because some cancer cells are left behind. Some of these cells are stem cells and can’t get killed with chemotherapy.
We have demonstrated benefit in patients with metastatic disease. When you take Avastin, tumors that are visible and big and need to grow up regulate VEGF which is bound away with Avastin. But what can Avastin do when the cancer cells are very small and don’t need VEGF to survive?
One discussion asks whether we should give adjuvant Avastin for a longer time. However there are also side effects seen when treatment with Avastin was extended to one year.
Erbitux also did not work. Why not?
I don’t think we have the answers, but it forces us to think about the difference of cancer and its microenvironment between cancer which has spread and is active and cancer which only exists in the form of a few cells somewhere.
We need to develop smarter therapies and how to select the effective therapy like we have begun to do in metastatic patients. Interestingly, KRAS mutation did not help to select patients who benefitted from Erbitux in the adjuvant setting . Maybe EGFR is not the right target? These results, even through disappointing will force us and industry to rethink and use our molecular biology of cancer to come up with more effective strategies.
Also, I want to mention diet, exercise and supplements in this setting. We need to invest more resources and research to understand what else we can do to reduce cancer recurrence. There are interesting data on exercise, aspirin, vitamin D and diet rich in vegetables. We need to systematically test these possible interventions.
In addition we need to develop a complete new class of medications which attack the colon cancer stem cells, because if they are not removed, they will cause recurrence. Research is going on at USC which may be successfully address this ongoing problem.