Drug Rescue by Biomarker-based Personalized Medicine

Biomarkers can rescue drugs by identifying the patients that respond to them. Herceptin, initially approved in 1998, emerged as a winner only a decade after clinical trials showed little or no efficacy and is now a billion dollar blockbuster. Only when the 20% to 30% of women whose tumors overexpress HER2 were singled out was the drug’s efficacy indisputable. In the pivotal clinical trial of patients with metastatic breast cancer, tumor-response rates to Herceptin plus chemotherapy were 45%, compared to 29% for chemotherapy alone.

But response is not wholly predictable. Reported response rates for HER2- positive cancers vary from less than 20% to more than 75%. HER2-positive cells that don’t respond to Herceptin may have more active forms of the kinase Akt. And HER2 belongs to a receptor family that can be activated by 11 different soluble proteins and combinations thereof. Researchers are already betting that working out the biology behind the biomarker will lead to better treatments. Another anticancer antibody based on this understanding is already in clinical trials.

Similarly, the lung-cancer drug Iressa (gefitinib) could be rescued by a diagnostic based on a biomarker. Unfavorable clinical trial results dashed high hopes for big sales, but finding the patients most likely to benefit changed prospects. Various studies found that patients that responded to Iressa had mutations in the gene for EGFR.