PLX4032

The NY Times is running a long series on this promising cancer drug, which is designed to shut down a particular aberrant protein created by a single genetic mutation, known as V600E BRAF. This mutation seems to be behind about half of melanomas and lesser percentages of other cancers. You can read a brief technical report on the drug here:

The Phase I study examined primarily melanoma patients whose tumors were shown on genetic sequencing to contain the V600E mutation. A total of 21 patients were treated with escalating doses of the drug. The drug appeared to be well tolerated at doses providing projected therapeutic drug levels, although dose limiting toxicity was ultimately reached. A small cohort (3 patients) of papillary thyroid cancer patients was also treated.

The results were remarkable. Of the 16 melanoma patients with the V600E mutation, 9 had partial responses , 6 had stable disease and one had progressive disease as their best responses. None of the 5 non-mutated melanoma patients had any responses. Also, of the three papillary thyroid cancer patients treated, one had a partial response and two had stable disease.

The clinical and radiologic effects were reported as rapid and dramatic. Tumor shrinkage at multiple organ sites were seen, including liver, lung and bone. (No patients with brain metastases were treated in this trial.) Several patients also had dramatic clinical improvement in symptoms associated with their disease, such as pain.

As with most Phase I trials of cancer drugs, the people being treated were very sick and considered beyond help with other methods, so that the drug was able to keep 15 of 16 patients alive and reverse the disease in nine is very impressive.

Our knowledge of the genetics of cancer has been growing for 30 years now without leading to much in the way of help for cancer patients. Perhaps this latest generation of drugs will change that.