Where are we with Targeted Cancer Therapeutics?

In a recent project, I received a draft manuscript discussing targeted cancer therapeutics and companion diagnostics in which the writer made this statement: ”CML patients in treatment with Gleevec now have the same life expectancy as people without the disease, while suffering few side effects”. I was aware that many CML patients respond well to imatinib (Gleevec), but wasn’t aware that imatinib effectively cured these patients, as this statement implies. If true, this is a stunning success. I am more accustomed to reports such as this paper on gelfitinib resistance or this one on imatinib resistance, which bolster the view that resistance to targeted therapeutics is essentially inevitable.

I took a closer look at the paper that this statement was apparently based on to convince myself. The publication that seems to have been the focu s of the attention that generated statements such as that above was published in the Journal of the National Cancer Institute in 2011. The first author, Caro Gambacorti-Passerini, and his colleagues analyzed outcomes in 832 CML patients who had been treated with imatinib. The figure that encapsulates this phenomenon is Figure 2 from Gambacorti-Passerini et al. J Natl Cancer Inst, 2011, 103:553, reproduced here:

Gambacorti-Passaro Figure

Panel A is the incidence for several types of leukemia/lymphoma, CML is indicated by black triangles; panel B shows mortality for the same diseases, with CML again indicated by black triangles.

Notice that the mortality of CML drop dramatically right around when imatinib was approved. We would like to do this with all cancers.

The caveat to the story that the writer in my project glossed over was that one of the enrollment criteria in the aforementioned study was that the patient be in complete remission at 2 years of treatment. That is to say, patients who did not respond to imatinib or relapsed prior to their 2 year anniversary were not included in the study. This criterion for participation means that this study examined survival of the patients with the very best response to imatinib. Now, it is still an impressive fact and excellent news for CML patients. It means that if you have a good response to imatinib, you are just as likely to succumb to another disease as to CML or, in other words, you have a normal life expectancy.

This got me to thinking. How are we doing with targeted therapeutics for cancer? Do other targeted therapeutics have a similar highly effective profile? Is the original statement that caught my eye just a narrow, subjective view of the situation for CML patients?

In upcoming posts I am going to take a closer look to see what lessons we might learn from this encouraging view of cancer therapy. I don’t think the effect will be quite as drastic for other targeted therapeutics, but I think it’s worth taking a look. Are those who respond well to some of these therapeutics essentially cured of their cancer? If not, what does the response look like and what does it say about where to go next. Stay tuned for future posts examining the impact of targeted therapies

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