From the Desk of Dr. Lenz
New Data on COIN
At the ECCO/ESMO meeting in Berlin the data on a large phase III clinical trial from the United Kingdom (COIN) was presented. It was a trial comparing FOLFOX or XELOX in combination with Erbitux.
It is important to know that in the UK Avastin is not approved, and Erbitux was only recently approved in patients with organ limited disease based on the chance of curative resections in patients initially deemed not to be resectable. However it is difficult to judge what the COIN results mean. The response rates in the patients with wild-type KRAS was significantly increased to 64%, so far so good. The problem is that the time to tumor progression and overall survival was not improved in patients with wild-type KRAS and Erbitux therapies.
I would caution not to jump quickly to conclusions since these data require a closer look. It is certainly surprising that about 40 percent of patients died in the first year which is much higher than any other study, which is usually about 20 percent, suggesting that these patients were sicker than in other trials.
In the UK, which reflects a pretty frugal health system, CT scans to monitor success of therapy are done every three months, not every six weeks as in United States or other parts of Europe. This makes it much more difficult to see a difference in results, particularly when we expect a time to tumor progression between 7 and 9 months. We also have to recognize that the CT findings are not centrally reviewed which means they can change when scans are reviewed by an expert panel (numbers always change from the investigator reading to an independent panel).
However the most interesting data are that the patients who received Erbitux and Xeloda had significant side effects leading to two dose reductions meaning that these patients received much less chemotherapy. This group seemed to have no benefit from Erbitux, but the patients who received FOLFOX did. We don’t know for sure why there are why are there more side effects with Xeloda and Erbitux, but both have overlapping GI and skin toxicities.Whether there is also some biological interaction we don’t know yet.
These data certainly need more evaluation and detailed review to be able to fully understand them.
Disclosure: C3 has accepted funding for projects and educational programs from Bristol-Myers Squibb and ImClone Systems in the form of unrestricted educational grants. C3 has ultimate authority over website content.
At the meeting in Berlin the data on a large phase III clinical trial from the UK was presented. It was a trial comparing FOLFOX or XELOX in combination with Erbitux. It is important to know that in the UK Avastin is not approved and Erbitux was only recently approved in patients with organ limited disease based on the chance of curative resections in patients deemed not to be resectable. However the COIN results are difficult to judge what they mean. The response rates in the patients with wt kras did significantly increase to 64% so far so good. The problem is that the time to tumor progression and overall survival is not improved in patients with wt kras and Erbitux therapies. I would caution to jump quickly to conclusions since these data require a closer look. It is certainly surprising that about 40% patients died in the first year which is much higher than any other study usually about 20% suggesting that these patients were more sick than usual. In the UK which reflects a pretty frugal health system, CT scans to monitor success of therapy are not done like in the US or Europe every 6 weeks but every 3 months which makes it much more difficult to see a difference particular when we expect a time to tumor progression between 7 and 9 months. We also have to recognize that the CT findings are not centrally reviewed which means they can change when scans are reviewed by an expert panel (numbers always change from the investigator reading to an independent panel). However the most interesting data are that the patients who received Erbitux and Xeloda had significant side effects leading to two dose reductions meaning that these patients received much less chemotherapy and this group seemed to have no benefit from Eribtux but the patients who received FOLFOX did. Why are there more side effects in xeloda and Erbitux we don’t know for sure but both have overlapping GI and Skin Toxicities whether there is also some biological interaction we don’t know yet. These data certainly need more evaluations and detailed review to be able to fully understand them.
This news article was originally posted on October 19th, 2009 and was accurate at the time of publication. Since then, information may have changed or links may now be outdated. Please call our Answer Line 1-877-427-2111 for the latest information, or talk to your doctor before making any medical decisions.
Posted by Heinz-Josef Lenz, MD on October 19th, 2009
Tags: cetuximab, clinical trials, COIN, Erbitux
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Catherine Schultz
October 20, 2009 at 12:38pm
Are you associated with the Erbitux people? If so it would be nice to have you mention your association even when we have good news about this drug.
Kate Murphy
October 20, 2009 at 6:17pm
We’re sorry. C3 does receive unrestricted educational and program grants from ImClone Systems and Bristol Myers Squibb.
Our editor forgot to include that disclosure in posting Dr. Lenz’s message. We’ve corrected the mistake.
Dr. Lenz also serves as a consultant to several corporations and receives honoraria from them. His disclosures are listed here.
Thank you for bringing this to our attention.