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.
April 28, 2009 at 9:16 am, Maen Addassi said:
I think the Avastin is a big bubble should be finished for example :
1. CRC with Oxaliplatin was not impressive.
2. Breast cancer with old product called Paclitaxel was given a good result but in the other hand with the newest & most common drug Docetaxel with a trial called Avado trial ; it seems the result was not so impressive they tried to promoted the Hazard ratio rather than a clinical result.
3. Lung cancer : at the beginning with Paclitaxel it was made a good survival a trial called E4599 by A Sandler published at 2006 at NEJM it is add 2 months for overall survival (from 10.2 to 12.2 ) with a double dose and of course a double cost
4. Renal cell carcinoma : same story; without any advantages regarding survival
Kindly note the British health system was refused Avastin for CRC due to lack cost effectiveness
Is it worth this!!!
April 28, 2009 at 9:34 am, j.d. said:
When will we have results from the NO147 trial? Is there any preliminary data at all?
I ask because I’m currently on Folfox with Erbitux after a R0 liver resection for stage 4 cc.
In fact, if you have any advice for people like me to improve our chances at preventing recurrence, we’d love to hear it! So much of it seems to come down to tumor biology.
April 28, 2009 at 9:34 am, Heinz-Josef Lenz said:
there is no doubt that some patients benefit signficantly from Avastin, we just need to learn who these patients are. To treat everyone the same is the past. HJL
April 28, 2009 at 9:36 am, Heinz-Josef Lenz said:
the study is still ongoing because it was stopped to amend the trial to only include wild type kras, based on biology FOLFOX erbitux is a great combination allowing synergism between oxaliplatin and erbitux. HJL
April 28, 2009 at 8:28 pm, jack straw said:
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.
What does the above quote mean? Is there a higher chance of recurrence with MSI?
April 29, 2009 at 8:37 am, Salvatore Salamone, Ph.D. said:
I couldn’t agree more that “to treat everyone the same is the past”. For instance in addition to the genetic advances that have been made to optimize treatment, recent studies have shown that by optimizing the dose of 5-FU to plasma target levels impressive results can be achieved with improved efficacy, lower toxicity, and improved survival. Pharmacokinetic dose adjustment is far less expensive than any new drug regimen and, it appears to provide higher benefit to patients. It is interesting to note that in discussions of tailored therapies that oncologists often talk of genetic advances and do not mention drug management of the dose to increase the drug’s effectiveness in spite of the promising results.
April 29, 2009 at 9:42 am, Heinz-Josef Lenz said:
MSI tumors have a lower risk of recurring therefore they do overall better. aboutt the PK/PD agree that we can optimize dosing and schedule for patients by monitoring pharmacogenomics and checking plasma levels. HJL
April 30, 2009 at 7:15 am, Anne Scheving said:
Dear Dr Linz,
I am desperate to get a second opinion for my mother from a multidisplinary team; she has metastatic colon cancer (recurrence in regional LN), but no spread to liver, lungs.
We are in Belgium but are happy to travel.
April 30, 2009 at 9:39 am, Heinz-Josef Lenz said:
Anne,there is a great clinic in leuven Dr. Tejpar is an outstanding GI Oncologist who I would strongly recommend to see. HJL
May 02, 2009 at 10:43 pm, Michelle G. said:
The issue in some cases is not even whether Avastin extends survival or not. In my husband’s case, taking Avastin allowed him to have surgery for Stage IV metastatic colorectal cancer which had spread to his liver. Prior to taking Avastin, he was considered inoperable and palliative. Drastic improvement in the outlook of things thanks to Avastin!
May 02, 2009 at 10:53 pm, heinz josef lenz said:
the problem is how do you know it was avastin and not the chemotherapy. since the response rate is the same for folfox versus folfox and avastin……..not that i think that avastin is a great drug we just need to know how to use it. in your husband case it could the chemo alone. HJL