The ALK mutation came back negative. According to the report there weren't enough cells that presented with the mutation for it be considered positive for ALK. HOWEVER, 63% of the cells tested "suggests ALK gene apmlification or plysomy of chromosome 2. The clinical significance of ALK gene amplification or chromosome 2 polysomy in patients with NSCLC is uncertain. Polysomy is not currently an indication for crizotnib therapy."
What exactly does this verbiage mean? Is there an ALK mutation present or not? what is amplification? and what is chromosome 2 polysomy? are these treatable with targeted therapy or immunotherapy? where can I go to research these specific details? are there clinical trials that work on this specific situation? or certain docs across the nation that are experts in this field?
Reply # - January 24, 2016, 04:06 PM
Hi Good-life,
Hi Good-life,
The ALK "mutation" is actually a rearrangement in which the ALK and EML4 genes are inverted. The reference in the report to "ALK gene apmlification or plysomy of chromosome 2" refers to a finding that there are extra copies of that gene. This is not the same as an ALK rearrangement, and as the report states, there is no evidence that this amplification results in sensitivity to crizotinib, and therefore treatment with crizotinib is not suggested.
I have not found any trials testing crizotinib efficacy in NSCLC patients with ALK amplification as opposed to rearrangements, although there is at least one study looking at that situation in other cancers, which can be found at https://www.clinicaltrials.gov/ct2/show/NCT02034981?term=alk+AND+gene+A… Unless further study reveals evidence that patients with such amplifications benefit from crizotinib, and unless the cells show some other targetable abnormality, such as MET amplification (for which crizotinib may be indicated, there is no targeted therapy available. Immunotherapy may be an option, and is something you may want to discuss with your doctor.
JimC
Forum moderator
Reply # - January 25, 2016, 06:43 PM
ALK rearrangement is uncommon
ALK rearrangement is uncommon, 4% of lung adenocarcinomas.
In contrast, ALK gene amplification is a common finding. It is probably seen in at least 20 -30% of lung adenocarcinomas. It has little practical significance for most patients.
It is proposed to be a mechanism of acquired resistance to Xalkori and other ALK drugs. In my experience, I find that patients who first present with both high ALK gene amplification and ALK rearrangement tend to progress quickly through Xalkori.
Reply # - January 25, 2016, 06:59 PM
Hello Dr Creelan
Hello Dr Creelan
thank you for your reply. Since I don't present with both ALK gene mutation and ALK gene amplification, rather I only present with the amplification or polysomy, do you think I would progress through Xalkori quickly? Is Xalkori a drug that might be worth me giving a try? just looking for clarification on your comment, some of it's over my head.
Also, I received a report today from Foundation One Medicine. It shows ERBB2 mutation, which I understand is also known as HER2. Also it showed RICTOR amplification. Do these results anything more to you that you could comment on? I'm curious how the entire picture is evolving now and what options are out there that may address my entire situation? Reports are showing ALK polysomy plus ERBB2/HER2 mutation and now RICTOR amplification.
Reply # - January 25, 2016, 07:33 PM
No, I would not suggest
No, I would not suggest trying the Xalkori currently for the ALK gene amplification/polysomy.
RICTOR is a gene involved in cancer cell proliferation. Relatively less is known about its clinical importance in lung cancer. There has been limited activity reported with mTOR inhibitors, mostly in the non-human lab setting. There has been durable stable disease reported in a handful of patients. Bottom line: I would only do this if it is part of clinical trial.
The HER2 mutation is more important. Drugs like afatinib have activity in this setting. There are several trials for HER2 mutation. You need to discuss the importance with an oncologist.