Avastin and Herceptin

[LauraP]

Is anyone on Avastin and Herceptin? I know that there are some trials out there regarding using the drugs together as maintenance. Has anyone been a part of those trials or have any input.

Thanks!

Laura

[Gina]

Have most of you seen this article?

The San Antonio Breast Cancer Symposium:
The Failure of Targeted Therapies—So Far
by Musa Meyer

One of the disappointments at San Antonio this year was the overall failure of some targeted therapies to show much in the way of treatment benefit when given either alone or with chemotherapy drugs to unselected patients. Because of those and similar results, scientists are no longer looking at single genetic factors but are focusing instead on the “crosstalk” between genes (see the section titled “Understanding Hormonal Resistance” in our story “The 25th Annual San Antonio Breast Cancer Symposium”).

Avastin (bevacizumab), also known as Anti-VEGF, is manufactured by Genentech and was recently studied for its effect on late-stage metastatic breast cancer. VEGF stands for vascular endothelial growth factor, a protein produced by one of the important genes that regulate angiogenesis, the process by which tumors create the blood supply they need to grow and thrive. In normal tissue VEGF is thought to be important in childhood development and in healing wounds--[like h. pylori induced lesion ulcers perhaps??], but in cancers that form solid tumors, angiogenesis is what enables tumors to get larger than the size of a small pea.

A phase III trial randomized 462 patients with metastatic breast cancer who had already received chemo (anthracycline and taxane) and gave them either the drug Xeloda (capecitabine) alone or Xeloda plus Avastin. The results were disappointing. Adding Avastin to Xeloda in heavily pretreated late-stage metastatic breast cancer patients had little effect. There were some treatment responses, but they didn’t translate into any clinical benefit in terms of increasing the time to disease progression or length of survival. Trials are being done in first-line metastatic breast cancer with the hope that Avastin can be more effective with earlier stages of the disease.

Sorry, I just haven't seen Avastin helping any of the her-2 mets folks here either...that is just my take for what it is worth.

Gina

[Joe]

Musa's article deals with patients who are HER2-

Regards
Joe

[StephN]

I was wondering what Gina was talking about.

[al from Canada]

Just to clarify.....95% of the studies on AVASTIN have been done on HER2 (-) patients. AVASTIN targets VEGF which may be over-expressed, or not at all, as is HER2, in a variety of cancers. All these cancers are different. For example, lung cancer can be HER2 positive but herceptin has no effect in lung cancers. Why??? They don't know but....

What we do Know as a result of study information revealed at SABCS by Dr. Slamon himself; that 70% of HER2 cancers also are also over-expressed VEGF; and that a study from a relatively small sampling of HER2 patients has demonstarted that AVASTIN has clear anti-tumour activity IN HER2 POSITIVE BC patients...enough so that when questioned at a discussion forum. he stated that adding avastin to herceptin in HER2 patients was their best shot at maximizing treatment, and by adding xeloda, even better.

What else you have to know is that these conclusions on avastin not working in BC are a result of critical errors in study design. Yes, avastin + xeloda didn't work but they were done in the general BC population. Assume that only 30% of that population was HER2 + and only 70% of that 30% was VEGF + then of course you will get lousy results. You also can't discount Kathy Millar's work on AVASTIN + TAXOL (E-2100) which showed a dramatic response.

One of the best expamples of this was with IRESSA, which is a HER1 antangonist. The sampling in which iressa was tested was far too large therefore it was never approved for BC. Many oncologists have seen the flaw in this study design and are starting to prescribe iressa off-label for things like brain mets in HER2 disease. Other more recent studies unvealed at SABCS show a high level of activity beween herceptin and iressa. Dr. Slamon himself talked about the importance of study design in order to properly target these designer drugs and get approvals. He stated that if herceptin. which was designed for HER2 BC, were tested in the general population, that is all BC patients, the drug that is so revered by all of us, would never have gotten FDA approvals.

We all have to make our own decisions given the available information BUT, just make sure you read the information accurately.

This is my last word on this topic,
Al

[LauraP]

Thank you so much for your information! You all are so knowledgeable, that is why I post here. Al, I appreciate all of your information as your approach appears thoughtful. You have given me so good information to move forward and do further research.

Laura

[Lisa]

Thank you Joe and Al for keeping the facts straight.

I've left a message with Dr. Pegram's trial supervisor and hope to talk to her early next week.

Love and light,

Lisa

[AlaskaAngel]

Thanks Al for the very clear explanation. I can't think of a better person to have taking care of Linda, or to have had at San Antonio.

A.A.

[cmn]

Hi -I had a partial remission while I was in the avastin herceptin trial at UCLA. It also kept me stable for almost 2 years. I am her2+ and er-/pr-. Remember that avastin and herceptin are synergistic. Sometimes drugs do not work as well alone. Ucla is currently recruiting for a phase 2 herceptin/avastin trial. Other people are getting this combo outside of the trial. Please feel free to contact me by e-mail. Regards, Carol

[al from Canada]

Thanks Carol,

This is very important information everyone should know. I think that given the lack of a "cure", the best we can hope for is exactly what you have achieved; that is, stable disease or NED until the next big break-through comes along. At this rate, it won't take another 2 years.

Do you have any new trial data (or rumours)
Al

[cmn]

Dear Al, I hope you are right about a new breakthrough. I will start a new clinical trial (BMS599626) in about 2 and a 1/2 weeks. I am a bit nervous because there is not a lot of data since this is only a phase 1 trial. So far only stable disease has been reported. I haven't been able to find much info about this new drug except that it is a tyrosine kinase inhibitor, works on Her2 and egfr and is the sister to Lapatanib (it is a different compound though). I also found this article today(the bms drug is mentioned at the end of the article):
http://pubs.acs.org/email/cen/html042405142325.html
(I am her2+ and er-/pr-) Does anyone have more information or has been in this trial? I have already met somebody who was in this trial and it did not work for her. There is a washout period of 28 days(no treatment)
which makes me even more nervous. Best regards, Carol

[StephN]

Hi Carole -
There was buzz at San Antonio this Dec. about new drugs to block Her1, Her3 and Her4 pathways. By getting a drug that has the potential to interrupt two of those pathways at the same time you have a better chance of overcoming the tumors.
Not everyone who is HER-2 positive realizes that the reason Herceptin can fail is that the cancer will figure out another pathway besides HER2 for its proliferation route. This is also a reason why those of us whose disease is STRONGLY HER-2 positive will normally do better on Herceptin than those who are less positive.

This is a little complicated and gets into the reasons for the testing by FISH that will actually count the copies of HER-2 within a cell.

Now that the researchers know something about WHY Herceptin can fail, they are off on other directions to see where else they can foil the cancer.

My best wishes for a positive outcome for you in this trial. I also entered a trial for hard-to-treat mets in a very early phase over 4 years ago and manged to have a complete response. So, if someone can do it - it may as well be you, yes?!