Mark G. Kris, MD


May 23, 2013

Therapeutic Targets

As part of the therapeutic theme, we are seeing many targets. Each target represents a smaller number of patients, but with more targets more patients can benefit. I believe we will find more information about effective drugs for patients with non-small cell lung cancer patients, patients with adenocarcinoma with BRAF mutations, and also a very interesting story emerging about the next generation of ALK kinase inhibitors. We are all excited about crizotinib for patients who have ALK fusions. But it appears that a number of equally impressive drugs have been found, and clinical trials with some of them -- LDK378,[2] for example -- are being presented at the meeting this year. LDK378 appears to be effective up front and is effective in patients who had benefit from, and then progression on, crizotinib.

Other trials of targeted therapies include, for example, a study of gefitinib, given to patients with EGFR wild type, and comparing their experience with that of patients who received pemetrexed.[3]As you would expect, patients who received pemetrexed had a better result. In that case, it was not so much about finding the target but that the absence of a target leads you to a more effective therapy, and in that case it was chemotherapy.

So, in summary, at this year's ASCO I believe we will see more focused presentations, more precise targets, and more about matching the individual patient's tumors and molecular profile with the targets. We will hear more about the immune checkpoint inhibitors, which was a big topic last year, and more about using those agents in patients who have tumors that show susceptibility either by infiltration of cytotoxic T cells, or the presence of the antigen that would allow the anti-PDL1 antibodies to do their job.

This should be an exciting ASCO. We will talk again after the meeting to share what we learned there.


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