A Bumpy Road for Lung Cancer Research in a New Molecular Era

[Guest LCSC Info]

A Bumpy Road for Lung Cancer Research in a New Molecular Era: Identifying Problems and Solutions

March 9th, 2012 - by Dr. Jack West

http://blog.lungevity.org/2012/03/09/a- ... solutions/

I teamed up with Dr. Ross Camidge from the University of Colorado to write a commentary piece that appeared in this month’s Journal of Thoracic Oncology, covering new challenges that have been borne of our new recognition that lung cancer isn’t one or two big groups but actually many, many subgroups. We also proposed some relatively straightforward and some larger efforts that could be undertaken to adapt to the new world of “molecular oncology” we now find ourselves in.

It was only a few years ago that the lung cancer community recognized the clinical relevance of tumor histology, but that is really only a very crude way to subdivide patients with lung cancer. More representative of the new world order is the work from the Lung Cancer Mutation Consortium, which looked the tumor marker profiles of approximately 1000 lung adenocarcinomas and developed a pie with much smaller subgroups, as shown here: (Click on the blog link above to view the graph)

Why does this matter? Because after decades of seeing rather disappointing results from treating many lung cancer patients the same treatment, we’re coming to recognize that we can do far better by treating targeted populations in a targeted way.

The problem is that it’s much harder to find and study small groups than large groups. However, the development of XALKORI (crizotinib) over the past few years as a therapy for just the 3-4% of advanced NSCLC patients with an ALK rearrangement provides an example of how this can be done successfully. But it is a big change: our old model of clinical research in lung cancer relied on offering the same trial of chemo X vs. chemo Y at hundreds of sites for a very broad range of patients with advanced NSCLC. These needed to be large trials because even if we saw a benefit, it was small and needed many hundreds of patients to make the difference statistically significant (and not always clinically significant). At that time, many local cancer centers could open this kind of trial with an expectation to enroll many patients. However, with small subgroups now of lung cancer patients, these same local centers will now have very few patients eligible for such a trial in a year, which making it infeasible (trials cost essentially the same to bring through the regulatory hurdles of activation whether they enroll many or very few patients). Instead, trials for narrow populations are only offered at one or a few sites in a country or the world. And that’s presuming you can identify such patients. Stepping back, if these trials are being done based on the presence of investigational molecular markers, how can we identify such patients if local oncologists can’t realistically know about and offer testing for everything emerging on the research horizon?

Dr. Camidge and I think we can answer this latter question pretty readily by leveraging online patient communities. Dr. Camidge did a webinar on the subject of molecular testing and ALK for GRACE in February, 2010, which was actually relatively early in the evolution of the story of ALK and clinical research with XALKORI. This activity was widely viewed (over 1000 times since its release, following good attendance of the live presentation), from there being disseminated to patients and caregivers throughout the online world. At the same time, participants in other online lung cancer communities also raised the visibility of this marker and research by discussing it throughout cyberspace. This then led to patients asking for the test from oncologists who likely had barely heard of ALK before that. More importantly, it led to some of them being identified as having this marker, which led them to Colorado from all over the country, and even some from other countries, for the opportunity to participate in the clinical research on XALKORI.

However, this requirement for travel remains a major barrier. Our current trials system generally requires patients to undergo most or all of their eligibility work up, then most or all of their care visits as part of the study, at the research center. This represents a major financial and practical hardship for patients and families. A far more efficient and cost-effective system would maximize telemedicine consults for as much of the workup and ongoing care on study protocol as possible. This would enable far more patients to participate in such research.

Dr. Camidge and I wanted to at least start the conversations that identify these problems and, more importantly, propose constructive mechanisms to overcome them. We’ll need to engage far more people if we have any hope of implementing them. But I’ll also have the opportunity to reach out to my oncology colleagues at this year’s ASCO conference, where I’ll be leading an educational session on the subject of physicians collaborating with online patient communities. I’m hoping that these efforts will lead to a converging sense of how we can adapt to these fundamental changes in how we define and need to study cancer.