Hi there, I have alk positive lung cancer, have been treated for two years since diagnosis with crizotinib, I had three very small brain mets last year treated with gamma knife, now I am showing very early progression in left lung and there are also two new tiny brain mets and uncertainty as to whether the original ones are also recurring and also uncertainty whether other spots on the MRI are vessels or new tiny mets, I am to have an MRI again in a month to try and resolve the uncertainties. My consultant has applied for compassionate use of Ceritinib in case I need a change of treatment but nothing is decided yet, continuing crizotinib for a while more and gamma knife for any mets is my hope to buy more time before moving to the next drug, My question is if I have to move on, is alectinib a better choice if I can access it than ceritinib. I have heard Dr Shaw say it is better for the brain. My oncologist has no plan to biopsy at present. I would hope that I might get to use Ceritinib and Alectinib sequentially as some patients have, is there any view on which is better to use first and which order may give the better chance of benefiting from both sequentially. I have watched your brilliant videos so I have a lot of the background information, just wondering if Dr West has any view on best chance sequencing order for the drugs, Thank you Alicia
Ceritinib v Alectinib - 1268973
aliciauk
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Reply # - March 19, 2015, 06:45 AM
Alicia,
Alicia,
I am sorry to hear of your progression. I hope that you can continue with Xalkori (crizotinib) for quite a while and that the brain mets are less than suspected.
Dr. West may express an opinion on your questions, but previously he has written that "There also isn’t any real evidence yet that other second generation ALK inhibitors work after Zykadia [ceritinib]." - http://cancergrace.org/lung/2014/04/30/new-approval-for-zykadia-ldk378c… In light of this statement, it may just be too early to know whether one of these agents is likely to be effective after use of the other, and which sequence would be preferred. And the question of whether one might be better than the other in treating or preventing brain mets would likely require a head-to-head trial comparing the response in patients in the same population, As Dr. West said in the same post, each of these agents is better than crizotinib in treating CNS disease:
"An additional important benefit of this agent, as well as several other second generation ALK inhibitors such as alectinib and AP26113, is that patients with brain metastases demonstrated responses. While XALKORI does not penetrate into the central nervous system (CNS), which is a “sanctuary site” in which we often see new disease appear in patients on XALKORI, Zykadia may be far better at preventing new disease from appearing in the CNS and can potentially treat pre-existing disease there."
Good luck with your scan and further treatment.
JimC
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Reply # - March 19, 2015, 07:09 AM
Thank you Jim, hoping Dr West
Thank you Jim, hoping Dr West might have something further to offer since that post last April even just his view on the basis of what limited information is available. Some people do get to use both drugs, in one of the acquired resistance patient forum videos in September Dr Shaw spoke about a patient moved for re emerging brain mets from ceritinib to alectinib and also of a different patient moved on (non brain I think) progression from alectinib to ceritinib. Thank you Alma
Reply # - March 19, 2015, 08:38 PM
Though Dr. Shaw is as
Though Dr. Shaw is as knowledgeable as anyone about ALK inhibitors, her perspective about the relative value of these agents is really limited to personal impressions based on a few patients here and there, not any definitive comparison. There is no new information to speak to the relative value of one over another in or outside of the brain. I wouldn't want you to put to fine a point on it, and I think Dr. Shaw would probably be uneasy with having her casual comments viewed as the absolute, definitive and divine word on these matters. These second generation drugs have not emerged as having distinctly different efficacy profiles.
-Dr. West
Reply # - March 20, 2015, 02:01 AM
Ok thank you Dr West
Ok thank you Dr West