Molecular Markers: The More You Seek, the More You Find

Howard (Jack) West, MD, Founder, President and CEO

Here's a video I just did in response to my recent spate of molecular marker studies I've sent in the last 4-6 weeks that have come back with quite a few positive results for an EGFR mutation or ALK rearrangement, as well as one patient positive for a ROS1 rearrangement.  For each of these patients, the results have had a major impact in the opportunity for them to receive an oral therapy with a high probability of response, and in a few cases, we've already seen a significant improvement.

The reason I made this video was that while I haven't found these mutations in a long-time smoker with a squamous cancer, I have been impressed by the range of patients in whom I've seen an "actionable" mutation.   Though some of the mutations were in never-smokers with an adenocarcinoma, quite a few have been in patients with a very significant smoking history and/or a poorly differentiated tumor.   And I've seen mutations more frequently than I might have anticipated.

I just had a long conversation with Dr. Horton, the pathologist at my institution who has a particular focus on lung cancer and who is very current on molecular testing.  We were discussing that we are living through some significant changes, in real time, that are still playing out.  Are we going to see the same patterns of which patients have mutations as we expand the tested population from few dozen in the initial reports to hundreds and thousands?  Are the growing number of places doing testing conducting these tests in the same way, so that the patients who are reported as ALK positive or EGFR mutation positive have the same high rate of response, or might we see a broader range of positivity with a lower response rate because it's diluted?  Are the general "rules" about mutations being mutually exclusive or being extremely infrequent in squamous histology going to hold true as we test more patients?

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As I mention in the video, it can be difficult to change your view, but I think that's the appropriate action to take if new information coming should lead to a change.  We don't want to be wishy-washy, but I think it's also a mistake to tenaciously hold onto perspectives that might have been appropriate based on the information available previously, but not necessarily as new information comes in.  I am happy that my views on molecular vs. clinical factors predicting response to oral EGFR inhibitors changed with the results from the IPASS trial, and as we learn more about molecular oncology, we should all recognize that the story is still being written, and that we need to be open to changing our views on the basis of new knowledge we're gaining in real time.

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craig's picture

_________________________________
Stage 4 ROS1+ [mucinous BAC] adenocarcinoma NSCLC since 2011
Xalkori (crizotinib) 5 yrs
Alimta (pemetrexed) + carboplatin (mere months)
TPX-0005 (repotrectinib) TBD (1+ years as of Fall 2018)

craig's picture

_________________________________
Stage 4 ROS1+ [mucinous BAC] adenocarcinoma NSCLC since 2011
Xalkori (crizotinib) 5 yrs
Alimta (pemetrexed) + carboplatin (mere months)
TPX-0005 (repotrectinib) TBD (1+ years as of Fall 2018)

 

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