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The ROS1 Mutation: A Target for a Small Population with Apparent Sensitivity to XALKORI

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After the last several posts have discussed our friend and lung cancer expert Dr. Ross Camidge, we’ll turn to the related topic of ROS mutations, which have been the subject of research by Dr. Ross Camidge (though apparently not named for him) and also researchers at Massachusetts General Hospital. This is a gene for a DNA repair protein, and the tyrosine kinase binding portion (the part that gets turned on to set off a cascade of downstream intracellular events) for ROS1 is very similar to that for ALK. In the lab, ALK inhibitors can also inhibit ROS1, and now the first few patients have been at the same centers that have done the initial work with XALKORI (crizotinib) — Massachusetts General Hospital, University of Colorado, University of California at Irvine, and now Peter MacCallum Cancer Centre in Melbourne, Australia — are also studying this agent in people with a ROS1 mutation. Apparently, the results with XALKORI in the few ROS1 mutation patients thus far are very encouraging, though this work hasn’t been published or presented yet in a large forum. Apparently Dr. Alice Shaw from Massachusetts General Hospital will be the lead author on a publication about to be published in the next week or so. I’ll share details when it’s available in the public domain.

How common is the mutation and who has it? Unfortunately, this group is so small that it makes the ALK positive population look big. It’s looking like about 1% of the lung cancer population, and these are again the patients who are never-smokers and have an adenocarcinoma, with pure bronchiololoalveolar carcinoma (BAC) also over-represented, younger patients, and perhaps a little more common in Asian than non-Asian patients. These are also patients who haven’t tested positive for EGFR, KRAS, or ALK, or other mutations being tested for by the Lung Cancer Mutation Consortium, for that matter.

ROS1 testing isn’t commercially available, and apparently at this time it’s pretty much limited to labs at Massachusetts General Hospital and the University of Colorado right now. Neither Drs. Camidge nor Shaw were recommending that broad screening should be done, but it is a stronger consideration for patients who have the clinical characteristics associated with a higher probability and who test negative for other mutations.

Stay tuned. We’ll have more on this in the next few weeks to months. It’s still very early in this developing story.


4 Responses to The ROS1 Mutation: A Target for a Small Population with Apparent Sensitivity to XALKORI

  • Craig says:

    FYI – A related news article mentioning the above blog article:
    http://seekingalpha.com/article/310533-pfizer-s-xalkori-the-story-can-only-get-better

  • Craig says:

    The research article you were waiting for in your blog entry has been published. Below are links to the abstract and to the citation for a related research article.

    (1) ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers
    http://jco.ascopubs.org/content/early/2012/01/03/JCO.2011.35.6345

    (2) ROS1 Rearrangements in Lung Cancer: A New Genomic Subset of Lung Adenocarcinoma
    http://jco.ascopubs.org/content/early/2012/01/03/JCO.2011.39.4197

    P.S. — I wasn’t mentioned in those articles, but I am a ROS1 mutation success. Dr. Alice Shaw nailed my mutation (rearrangement) on the 1st test she did for me, and crizotinib has been working very well for me as 1st line treatment. Based on my personal experience, I recommend triple-negative (not KRAS nor EGFR nor ALK) never-smoker adenocarcinoma patients consider getting ROS1 testing for this trial (either at MGH in Boston by Dr. Shaw or via another participating location), especially if at an incurable stage or match the ideal profile described in the articles. I believe the trial description can be found here: http://clinicaltrials.gov/ct2/show/NCT00585195

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