A news release from last Wednesday stated that the clinical trial of NSABP C-08 was negative.
This was the clinical trial testing whether the addition of Avastin to FOLFOX would increase efficacy in reducing recurrence for patients with stage II and III colon cancer. FOLFOX was given over 6 months compared to FOLFOX in combination with Avastin for 6 months, followed by additional 6 months of Avastin. There was a great hope that this anti-VEGF therapy would further decrease tumor recurrence.
This is a little bit surprising, since the addition of Avastin increased efficacy of many therapies for different cancers including lung, breast, colon and head and neck cancer. However looking closer in colon cancer, a recent company-sponsored study showed that the addition of Avastin did not increase response rates and did not increase progression free survival when combined with FOLFOX and there was no overall survival benefit. Therefore, it may be this combination is not as effective as we hoped for.
The exact details of the clinical trial will be reported at the Annual Meeting of the American Society of Clinical Oncology in Orlando in May 2009. This is the largest oncology meeting in the world with more than 25,000 oncologists attending from around the world. This meeting reports the newest data and sets new standards for the treatment for patients with cancer.
This is another lesson we have learned that the treatments we use for patients with metastatic colon cancer can not always be translated into benefits in the adjuvant setting. Our own group will present data at ASCO on how to predict efficacy of FOLFOX/Avastin in patients with metastatic disease. We found gene expression levels of genes involved in the DNA repair and in different growth pathways make a difference in response to Avastin and FOLFOX.
In the future we need to select patients who really benefit from chemotherapy by testing tumors for sensitivity. We have made a great progress with testing for KRAS but this is only the beginning. We have some preliminary data showing in addition to MSI and 18q deletion that will recur after successful surgery and being treated with adjuvant chemotherapy.
There is one other big trial in adjuvant chemotherapy ongoing, N0147, which is using Erbitux instead of Avastin. We are eagerly waiting to see whether this combination will be more successful.
Despite this negative Avastin trial, the future for colon cancer therapies is looking very promising with novel drugs being developed and new genetic advances which help us to tailor chemotherapy to increase efficacy and decrease toxicity.