FDA Approves Two Dako Assays As Companion Diagnostics For Genentech's New Breast Cancer Medicine Kadcyla

Companion Diagnostics for Kadcyla

The area of pharmacogenomics was ripe for proprietary tests invented alongside a drug and owned by the drug developer and/or a partner in the diagnostic field.

HercepTest uses immunohistochemistry (IHC) analysis for the detection of HER2 protein over-expression in breast cancer. It measures the level of proteins in cancer cells providing clues about which therapies are "likely" to have clinical benefit.

HER2 IQFISH pharmDX is a direct fluorescence in situ hybridization (FISH) assay, It uses breast carcinoma specimens (FFPE) stained with HER2 IQFISH pharmDX. FISH is used to examine gene copy number variation in the tumor.

These tests serve as a companion diagnostic tool to identify cancer patients with HER2-positive metastatic breast cancer who "may" be eligible for Kadcyla treatment.

Because the results of the IHC test can sometimes be ambiguous, many doctors suggest the FISH test for a second opinion. Tumors that are 3+ positive by IHC and those that test positive by FISH are most likely to benefit from HER2-inhibitors.

Tumors that test 1+ by IHC are considered HER2/neu negative and those that test 2+ are considered equivical, in which case FISH testing is done to make the determination.

Tumors that test negative for HER2/neu by FISH are "unlikely" to benefit from HER2-inhibitors.

Either test examines "dead" tissue that is preserved in paraffin or formalin. According to a professor of translational genomics at the Scripps Research Institute, specimens obtained from biopsy or surgery are formalin-fixed, paraffin embedded (FFPE). FFPE ruins sequencing capabilities, denatures everything, and ruins the samples.

How is that going to be predictive to the behavior of "living" cells in spontaneously formed colonies or microspheres? Can it describe the complex behavior of living cancer cells in response to the injury they receive from different forms of chemotherapy? There is a big difference between "living" and "dead" tissue.

All the gene amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don't tell you if one drug inhibitor is better or wrose than another drug inhibitor which may target this.

No gene-based test can discriminate differing levels of anti-tumor activity occurring among different targeted therapy drugs. Nor can an available gene-based test identify situations in which it is advantageous to combine a targeted drug with other types of conventional cancer drugs.

The cell is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems’ response to drug treatments, not just one target or pathway.

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