peterz54
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Posts:12
A patients daughter just told me that her mother's primary tumor (colon) was tested as K-RAS mut, but her liver was biopsied as K-Ras wild type, and therefore she was put on an EGFR inhibitor. This has not been suggested to my wife even though she has significant liver mets, only that EGFR inhibitors are not an option for her due to her being Mut.
I have not seen this treatment option disussed in all the literature I have read. Is it uncommon for secondaries to be WT when primary is Mut, and she just got lucky? And does it make sense to be treated with an EGFR with a Mut primary?
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Reply # - August 12, 2012, 02:39 PM
Reply To: K-Ras mut primary vs K-Ras wt secondary?
Hi peterz54,
Dr. West wrote a recent post on mutation testing: http://cancergrace.org/lung/2012/08/02/heterogeneity-and-mixed-response/ In that post, he points out that EGFR testing (and by analogy, testing for any mutation) is not foolproof in that a negative result can be obtained if the "wrong" part of a tumor is tested, and it is also possible for some of the cancer to be mutation positive while other parts are not. So it is possible that there are both EGFR TKI resistant cells and sensitive cells in the same location. As long as there are cancer cells bearing the mutation, an EGFR TKI tends to be a good option, but another agent may be necessary to control the resistant cells.
JimC
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Reply # - August 12, 2012, 02:57 PM
Reply To: K-Ras mut primary vs K-Ras wt secondary?
In the setting of colon cancer, there isn't apparent value in being on an anti-EGFR antibody if a person has a KRAS mutation (or at least any other than a particular one known as G13D). In most cases, there haven't been multiple areas tested, so it's really not known how often in colon cancer the results are different when 2 or 3 areas are tested. It's not the majority of cases, however, because in people who are KRAS mutation positive, there really doesn't seem to be any benefit from an anti-EGFR antibody -- it's not just as if the results are good but not quite as good as in those with KRAS wild type.
It's worth bearing in mind that 1) these agents are absolutely not miraculously beneficial even if they do provide what we'd consider a meaningful benefit for those with KRAS wild type, and 2) there aren't data out there to say that someone who has two biopsies, one showing a KRAS mutation and one showing KRAS wild type, will do well because they get an anti-EGFR antibody. While it might be enough to enable them to get the drug, whether they benefit from it likely depends on whether most of their cancer is KRAS wild type or KRAS mutated...
It's becoming clear that the more biopsies we do, the more we recognize that there can be molecular heterogeneity in the findings. But I do think it's telling that there just isn't any benefit that is visible with KRAS mutated colon cancer patients getting anti-EGFR therapy -- suggestive that there isn't a subpopulation in that group that is truly benefiting and would be deprived of a great treatment if they don't get it.
--Dr. West