Evolving Biologic Diversity Generates New Challenges
Published Online: Tuesday, October 16, 2012
D. Ross Camidge, MD, PhD
Director, Thoracic Oncology Clinical Program, University of Colorado, Denver, CO
D. Ross Camidge, MD, PhD, director of the Thoracic Oncology Clinical Program at the University of Colorado Denver, has been at the forefront of efforts to identify driver mutations and develop therapies that target those abnormalities.
In 2009, Camidge helped define the impact of rearrangements in the anaplastic lymphoma kinase (ALK) gene in non-small cell lung cancer (NSCLC) (J Thorac Oncol. 2009;4:1450-1454). He then played a leading role in the clinical trial that led to the FDA’s approval last year of crizotinib (Xalkori), the first ALK inhibitor for advanced NSCLC.
This year, the Bonnie J. Addario Lung Cancer Foundation honored Camidge with its fifth annual lectureship award during the 13th International Lung Cancer Congress. In announcing the award, the foundation leadership said Camidge is “a relentless advocate of molecular testing, redefining the standard of care for lung cancer, and aligning lung cancer patients with targeted treatment regimens.”
In his presentation at the congress, Camidge said the heterogeneity of lung tumors generates challenges in terms of the costs and logistics of developing targeted therapies, given that relatively few patients may harbor a particular mutation.
Camidge said multiplex testing is needed, but there may be regulatory requirements to validate each element of an assay before a panel is approved. In addition, he said participation in clinical trials could be enhanced by “leveraging patient communities” through Internet tools and by making the delivery of care more accessible through telemedicine and a hubstyle research network.
In this interview with OncologyLive, Camidge further discussed emerging issues in molecular testing and drug discovery.
OncologyLive: Please give us a little history about the groundbreaking molecular testing program that you and your colleagues at the University of Colorado Denver established.
Camidge: We started testing every patient with nonsmall cell lung cancer regardless of histology starting in early 2008. The menu was pretty short to begin with. We did direct sequencing for EGFR and for KRAS. We did p53 as well at that time, although that sort of dropped off the menu a little bit.
By 2009, we started doing ALK-FISH [fluorescence in situ hybridization] testing because we were one of only two sites in the United States that could really get that assay up and running, and we helped to optimize that assay. And then very quickly, with the Lung Cancer Mutation Consortium coming on board, we took on board the snapshot platform for multiplex testing of mutations, and it’s still a constantly expanding menu.
We now have FISH testing for ALK, for ROS1, for MET gene amplification, and we have RET gene rearrangement FISH testing coming on board any day now.
Which patients do you test for molecular mutations?I tend to test everybody with advanced-stage disease, mostly stage IV, but people with stage III because I think they’re very likely to relapse. I test all histologies, partly because these assays are multiplex, so you don’t have to think about whether you should do a PI3 kinase assay on a squamous, and an EGFR on an adenocarcinoma. It’s just one big assay, and I do that when they walk through the door.
I think we’re shying away from testing stage I patients. We think it’s probably a waste of money because most of those are likely to be cured. It’s slightly controversial as to whether you should test nonadenocarcinomas. I think you should test them, partly because deciding on whom to do a definitive molecular assay on the basis of a subjective determination of histology makes less sense to me.
There are a lot of data showing how often pathologists, particularly community oncologists, will disagree about the histology. So I don’t think we should decide on whom to do a definitive test on the basis of a nondefinitive test.
Would you test for a panel of mutations?I would test for a panel of mutations for two reasons. One is you actually use up more tissue if you do sequential assays, so you get more “bang for your buck,” and you don’t waste as much time. And, secondly, the cost effectiveness gets much better as your hit rate, albeit for a series of different abnormalities, goes up dramatically for only a minor increase in the cost.
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