Replies to post #82988 on Biotech Values

[p3analyze]

Dew, Question for specificity

Dako markets the EGFr test because it’s a good business—not because it’s good science.
The statement is a bit of extreme. IHC testing is such a useful tool that not only is it used for EGFr testing, but also for HER2+ receptor testing. Breast cancer patients will not receive trastuzumab unless it's 3+ IHC (admittedly there is a small fraction of patients that are FISH+ but IHC2+). And the EGFr IHC testing is no different from HER2+ except for the ligand. Clearly, there are scientific values for the tests.


This is another way of saying the same thing: extremely low levels of EGFr (even levels below the level of detection of the commercial assay) may be sufficient to allow a patient to respond to an anti-EGFr drug.

This statement essentially mocks the collective intelligence of scientists at IMCLONE, BMS, Amgen, Dako and FDA. The line has to be drawn somewhere. I'd rather believe if the test is negative, it has to have high probability of identifying a negative sample, otherwise the assay is useless and should not have been marketed. If the specificity is 90%, then 90% of the EGFr-negative patients will not respond. Again, I ask how prevalent do oncologists treat without testing for EGFr positivity.

[DewDiligence]

Addendum re the direction of personalized medicine:

The discussion in the last few posts illustrates the sharp contrast between older implementations of personalized medicine, such as EGFr-expression screening, and newer implementations, such as testing for the K-ras mutation. The contrast is especially notable in that both implementations are germane to the class of anti-EGFr drugs (Erbitux, Vectibix, and Nimo).

In general, the former kinds of implementations are poorly defined (e.g. EGFr expression is not a true biomarker, but rather an arbitrary cut-off value of an assay) and have weak predictive value, while the latter kinds of implementations are biomarkers in the literal sense of the word and have strong predictive value.

Over time, we should see more and more implementations of personalized medicine that are similar to the K-ras test, and fewer and fewer that are similar to the EGFr screening specified in the FDA labels for Erbitux and Vectibix. This trend pertains not just to the treatment of metastatic colorectal cancer, but also to medicine in general.