Replies to post #142398 on Biotech Values

[biomaven0]

this class of drugs works very well to retard tumor progression for some cancer subgroups, while at the same time significantly accelerating closely related tumors

I'd like to see more evidence for this claim. Showing that one subgroup does much better than another doesn't imply that the drug is actually making the inferior subgroup worse.

Peter

[genisi]

Interestingly the lesson I take away from this is that if you are putting such drugs through the clinic it behooves you to predefine a set of subtypes and check. If you do this you are likely to find some stellar efficacies and some subgroups to stay away from.

In this paragraph you have summarized the essence of tailored targeted therapy. Since cancer types can be divided into subcategories and further by the molecular signals driving each one, plus we know there is heterogeneity not only between but also within tumors, clearly therapies need to be more precise. People in the industry understood that and Roche Diagnostics is an example of implementing this: Roche is already developing the vast majority of its new molecules with a companion diagnostic in order to defined population groups to a drug's MoA as early as possible, because of all the obvious advantages (better early stage detection, finding likely responders/non-responders, improve patient outcomes, shorting development process, finding the better combination, and even improve reimbursement).

[iwfal]

Kinase acting drugs

About the only such drug for which I looked for this effect and did not find it was Nexavar and its compatriot.

After hours searching there does, in fact, appear to be reasonably little regarding use of kinase profile to predict efficacy of VEGFR inhibitors. E.g. I did find one such purported paper - but amusingly (and frustratingly) it doesn't actually answer the question it says it is answering.

Purpose: No biomarkers have been identi?ed to predict outcome with the use of an antiangiogenesis agent for cancer. Vascular endothelial growth factor (VEGF) genetic variability has been associated with altered risk of breast cancer and variable promoter activity. Therefore, we evaluated the association of VEGF genotype with ef?cacy and toxicity in E2100,...

Results: The VEGF-2578 AA genotype was associated with a superior median overall survival (OS) in the combination arm when compared with the alternate genotypes combined (hazard ratio
0.58; 95% CI, 0.36 to 0.93; P
.023)...

I.e. they never tested whether: a) the drug works better in that genotype, or b) whether that genotype just lives longer, despite that being the claimed purpose of the study. (and, no, this wasn't just a poorly written 'results' section - the body of the paper is no better.). Yet is still published in a reasonably high Impact Factor, peer reviewed, journal.

PS All that said, the paper does possibly highlight an aspect that might matter - that for some drugs the efficacy of the drugs may depend more on the patient's genome than the tumor's.