Article and Video CATEGORIES
Please Note: New Treatments Have Emerged Since this Original Post
Thus far, the vast majority of patients who have an initial response to EGFR tyrosine kinase inhibitors like Iressa and Tarceva will eventually become resistant to them. At this year’s ASCO, our huge annual US-based oncology conference, a report was made by the group at Memorial Sloan Kettering Cancer Center (Riely abstract here) on a small series of patients who had progressed after a prolonged period of responding to Iressa or Tarceva. They found that patients who had slow progression, generally without symptoms, and then came off of their EGFR TKI therapy would often experience a rapid worsening of symptoms.
In general, we don’t continue drugs on which patients are showing progression, because we consider the drug ineffective at that point, but in this case it could just be a less effective set of brakes that is still better than not having them. In some cases in oncology, we do routinely continue drugs after patients have shown progression, such as men who initially responded to hromone therapy for prostate cancer and then continue on hormore therapy, or women with breast cancer who progress on chemo with Herceptin and are then often put on another chemo approach with Herceptin. We really don’t know the best way to manage situations like this. The early evidence suggests that approximately half of the patients with an initial response to EGFR TKIs who then progress seem to develop a defined mutation, called T790M, that makes drugs like Tarceva no longer fit as well as it previously did to the EGFR target protein. At this point, it is not clear if there is a way to reverse that process and have patients respond again to EGFR inhibitors. In lab models, some “irreversible” inhibitors of EGFR, such as a drug made by WYeth that goes by the catchy name HKI-272, seems to have encouraging activity in the test tube models. It is being tested in patients at a few centers around the country right now. The new agent Tykerb (lapatinib), which blocks both EGFR and another receptor in the same family known as HER-2 and has demonstrated activity in patients with breast cancer who have been previously treated, may bind to EGFR anfter it develops the secondary mutation. Still, at this point we haven’t seen how these and other potentially helpful drugs perform in real people who have stopped responding to drugs like Tarceva or Iressa. A further complicating factor is the evidence thus far that adding chemo and drugs like Iressa or Tarceva at the same time may lead to antagonism of each other, which would make it problematic to just add new chemo while keeping the EGFR TKI therapy ongoing. Perhaps adding the anti-angiogenesis agent Avastin or another agent targeting EGFR like cetuximab (an IV monoclonal antibody against EGFR) can be combined with EGFR TKIs and improve results, but at this point nobody has a clear answer of a best way to proceed in these cases.
Please feel free to offer comments and raise questions in our
discussion forums.
Forum Discussions
Radiation + Brain Operation has just been discarded due to high risk. They will double Tagrisso dosis and then wait to see if it works, then try traditional Chemo. I would...
Hi and welcome to GRACE. I'm sorry to know you are entering a new stage. I'm not about to comment just now but wanted to let you know I see your...
Edit to say, we can't give advice but we can comment with views and facts. :)
My first thought is to ask if she has been seen at a large...
Hi Barbro, Welcome to GRACE. I'm sorry you're worrying about this. We aren't able to give feedback on scan reports. Interpreting scan reports in this setting is not only unethical but...
Thank you, Janine, for answering so rapidly. I am aware that my nodules are small, but they scare me all the same. Your words that nodule measurements may vary somewhat when...
Hi Barbro, I'm sorry you're worrying about this, and don't feel like you can discuss this with your doctor. Speak to your doctor about this. Let them know your worries and...
Hi Bluebird, Welcome to GRACE. I'm sorry you're going through this scare and hope it's just inflammation or from an infection you didn't know you had.
A CT would be...