1. This drug, also known as Lapatinib, amongst other names has been one of the better Tyrosine Kinase inhibitors out there, which blocks both the EGFR (ErbB1) and Her2(ErbB2) receptors, unlike Gefitinib (Iressa) which has been shown not to be as impressive in many types of cancers, including Breast, where EGFR and Her2 are known to be overexpressed. So, many companies including BMS, Array Pharmaceuticals etc have several "broad range" tyrosine kinase receptor inhibitors in the pipeline. It all looks very promising.

Posted at 11:49AM on Feb 6th 2007 by Dmitriy

2. Exciting results have come from studies of multitargeted tyrosine kinase inhibitors, "small" molecules that act on multiple receptors in the cancerous cells, like Tykerb and Sutent. The monoclonal antibodies like Herceptin and Erbitux are "large" molecules. These very large molecules don't have a convenient way of getting access to the large majority of cells. Plus, there is multicellular resistance, the drugs affecting only the cells on the outside may not kill these cells if they are in contact with cells on the inside, which are protected from the drug. The cells may pass small molecules back and forth.

Each of these new targeted drugs are not for everybody (just like conventional cancer drugs are not for everybody). Even when the disease is the same type, different patients' tumors respond differently to the same agents. As the saying goes, "don't throw out the baby with the bath water." If a drug works extremely well for only 10% of cancer patients, identify which 10%. If one drug or another is working for "some" people (not average populations), then obviously there are others out there who would also benefit.

Posted at 5:05PM on Feb 6th 2007 by Gregory D. Pawelski

3. I am not sure that overexpression of a specific receptor (say ErbB1) would place a patient into a 10% category. These "dirty" inhibitors should have wider range of activity, since their specificities are nowhere near that of the antibody, which can be thwarted with polymorphisms etc, lowering the specificity, making antibody treatments more targeted and more specific. So, TKIs, as long as they target multiple pathways should find a wider patient pool, where they are effective.

Dmitriy
http://www.refuter.com

Posted at 8:30PM on Feb 6th 2007 by Dmitriy

4. Whether it be 10, 20 or 30%, the point is "targeted drugs are not for everybody." Pre-tests, like the EGFRx™ Assay, can help identify the individual cancer patient the drug works extremely well for, or it can tell that the drug is resistant. This could be Tykerb, Tarceva, Iressa, Sutent or Nexavar, because of being small molecule drugs. It is important to "personalize" cancer treatment, and this can be accomplished by "testing the tumor first."

Posted at 11:13PM on Feb 6th 2007 by Gregory D. Pawelski

5. Is there any fresh new on Tykerb? I've been following the progress of this drug because I'm Her2 and hopeful of a treatment, this time, in the form of a Pill. When do you guys think it will become available for early stage breast cancer?

Posted at 8:18AM on Feb 8th 2007 by Jeane

6. Oh yea, here is a link to NEJM article that is very recent. http://content.nejm.org/cgi/content/short/355/26/2733

"Conclusions Lapatinib plus capecitabine is superior to capecitabine alone in women with HER2-positive advanced breast cancer that has progressed after treatment with regimens that included an anthracycline, a taxane, and trastuzumab. (ClinicalTrials.gov number, NCT00078572"

And from what I understand it is a 1250mg daily dose in a pill form...


Dmitriy
http://www.refuter.com

Posted at 11:35AM on Feb 8th 2007 by Dmitriy

7. Is Tykerb FDA approved, and if not, where is it in the cycle? Thanks.

Posted at 3:34AM on Feb 22nd 2007 by Patrick

8. also waiting for, trying to find lapatinib

Posted at 4:38PM on Feb 21st 2007 by ann

9. FDA Approves Tykerb for Advanced Breast Cancer Patients

http://www.fda.gov/bbs/topics/NEWS/2007/NEW01586.html

What is of particular note is that monoclonal antibodies (like Herceptin) are large molecules that attach to specific proteins on the outside of cancer cells and do not have a convenient way of getting access to a large majority of the targeted cells on the inside, which are protected from the drug. Plus, there is multicellular resistance, the drugs affecting only the cells on the outside may not kill these cells if they are in contact with cells on the inside. The cells may pass small molecules back and forth. This would be a very good reason Tykerb may be much better than Herceptin.

Posted at 9:15PM on Mar 13th 2007 by Gregory D. Pawelski

10. greg, would it be totally unwise for someone with her2 stage2 breast cancer to just take Tykerb instead of Herceptin? I'm tantalized by the fact that it attacks small molecules, works even when herceptin stops working, and is in PILL FORM!

Posted at 8:33AM on Mar 15th 2007 by Jeane

11. Jeane. I thought about that myself. But the FDA says that Tykerb is only for Herceptin resistance. I have a lot of problem with that. The small vs large molecule may have some great significance. Targeted "small-molecule" therapies ruled at the last annual ASCO meeting of oncologists. The trend is away from the monoclonals to the small molecules.

Having said that, the study of cell function analysis tells us that even when the disease is the same type, different patients' tumor respond differently to the same agents. Herceptin (or any other large molecule targeted drug) may be more beneficial to some patients than Tykerb, Sutent, or any other small molecule targeted drug.

It's ultimately up to the physician to get as much information he/she can get to come up with a rational decision. Gather up all the information you can research and present it to your physician. Diagnostic tests are just that, tests. Not treatment. A physician can use all the necessary diagnostic evaluations they can get.

More and more physicians and patients are turning to individualized therapies to treat cancers. Without individualized testing, it's difficult to determine which drugs are best for patients who don't respond to standard therapies.

Posted at 5:13PM on Mar 15th 2007 by Gregory D. Pawelski

12. A pretty good resource for some diverse information on cancer is this site:

http://xooxleanswers.com/cancer.aspx



from an online research service. It has links to an assortment of interesting research on breast cancer and other cancers -- causes, statistics, treatment -- and more links are added regularly.

Hope it's helpful.

Posted at 11:15PM on Mar 15th 2007 by david

13. Cancer Drugs' Spectacular Costs Shifting Market Dynamics

Tykerb (lapatinib) is one of the first oral agents with the potential to compete directly with the IV drugs which is both a high-volume and high-revenue part of office-based practices. Early use of Tykerb will likely be limited to patients whose breast cancer is refractory to Herceptin (trastuzumab). In the longer term, it could supplant or perhaps find a place in combination with Herceptin.

Of course, will patients be able to afford the cost of these drugs? Herceptin's wholesale price on an annualized basis is approximately $45,000 per year. Tarceva, $40,000 per year. Nexavar, $60,000 per year. Avastin, $47,000 per year. Will the price of Tykerb approximate these novel agents or exceed their costs? The problem is not unique to these drugs, but also to all of the new molecularly-targeted agents.

Lee Newcomer, former chief medical officer and currently an executive with United Health Group, stated at the 12th annual conference of the National Comprehensive Cancer Network, that "Avastin improves outcomes in about 20% of patients, but we have no idea which cancer patients will benefit from a course of treatment. Because Avastin is included with numerous drug cocktails, it costs $354,000 per year of life extended with Avastin because of today's 'cookie-cutter' approach to chemotherapy. You don't know in advance who is going to respond."

Everyone is scared to death (and rightly so) at what is going to happen to the healthcare economic system with the introduction of increasingly expensive new drugs that benefit only a small percentage of patients who receive them, hence the headlong rush to develop tests to identify molecular predisposing mechanisms whose presence still does not guarantee that a drug will be effective for an individual patient. Nor can they, for any patient or even large group of patients, discriminate the potential for clinical activity among different agents of the same class.

Profit is a powerful motivating force. Among medical benefit payors, the profit motive is entirely consistent with the goal of developing a molecular test, which is to identify efficacious therapies irrespective of drug mark-up rates.

The FDA finds themselves under increasing pressure to allow new drugs into the marketplace, while at the same time protecting the safety of potential recipients of those drugs and also the financial interests of those who will have to pay for them. The pressure is so great that companion molecular diagnostics approved often have been mostly or totally ineffective at identifying clinical responders (durable and otherwise) to the various therapies.

It should be in the FDA's interest in saving the healthcare system perhaps billions of dollars a year (and thereby the healthcare system itself) by ensuring that expensive treatments are used appropriately. It should serve their interest not only in discovering new cancer treatments, but also using currently-available cell culture technologies to improve the effectiveness of existing drugs and save lives today by administering the right drug to the right patient at the right time.

The methods of cancer medicine during the last thirty some years are coming to haunt the "one-size-fits-all" establishment. Technologies, developed over the last twenty years by private researchers, hold the key to solving some of the problems confronting a healthcare system that is seeking ways to best allocate available resources while accomplishing the critical task of matching individual patients with the treatments most likely to benefit them.

Posted at 11:21AM on Apr 1st 2007 by Gregory D. Pawelski

14. Mr. Pawelski, please provide a link to this that you directly quote:

"Because Avastin is included with numerous drug cocktails, it costs $354,000 per year of life extended with Avastin because of today's 'cookie-cutter' approach to chemotherapy. You don't know in advance who is going to respond."

I'm especially interested the words that come after the word Avastin.

I would be interested in knowing if the words after AVASTIN were added by someone other than the author of the quote to make a point. If I am off base on this one, I apologize.

Thank you.

Posted at 11:17AM on Apr 1st 2007 by hchcec

15. Bigger guns than me are being aimed at the issue. United Healthcare has found some pretty disquieting things about the use of some big time biotech drugs. It's former Chief Medical Officer and currently an executive with Minneapolis-based United Health Group (one of the leading medical insurers), Lee Newcomer, at the recent NCCN meeting cited a number of striking figures.

http://www.sciencedaily.com/upi/index.php?feed=Science&article=UPI-1-20070316-20215500-bc-us-cancercosts-analysis.xml

Posted at 5:50PM on Apr 1st 2007 by Gregory D. Pawelski