In an interesting new trial funded by Genentech, vemurafenib, a skin cancer drug showed positive results in certain kinds of lung cancer and some other malignancies. The trial was based on a new concept of targeting gene mutations common to many cancers.
Current cancer therapies are usually specific to the type of cancer
Most clinical trials test the effect of the drug on a single type of cancer. Lately, advances in gene therapy made it possible to study cancer at its most fundamental level⎯genes. Scientists believe that although cancers may show organ heterogeneity, many of their molecular mechanisms have common genetic origins. For example, a genetic mutation called the BRAF V 600 is found to be present in many cancers.
BRAF is gene that makes the protein B-Raf, which when functioning properly prepares a cell for its death. An aberration in this mechanism sends the cell life-and-death cycle askew, leading to the development of cancer.
The Genentech clinical trial design
The clinical trial, also called the “basket” trial, attempted to test vemurafenib⎯a drug already approved for the treatment of melanomas showing the BRAF mutation⎯in other cancers with the same gene defect. Vemurafenib was developed by Plexxikon and marketed by Genentech under the name Zelboraf. A total of 122 patients with BRAFV 600 mutation-positive, non-melanoma cancers were enrolled in this open-label clinical trial. At the end of the study they were testes on the basis of response to cancer, survival without disease progression, and overall survival.
The clinical trial yielded mixed results
The study tested the drug effects on seven types of tumors. Among them, non-small-cell lung cancer showed a high response rate of 42%; the median survival time before progression of the disease was 7.3 months. Another group of cancer-like conditions⎯Erdheim–Chester disease or Langerhans’-cell histiocytosis⎯showed a 43% response rate and median treatment time of 5.9 months, with no one showing disease progression during this period. There were some anecdotal results with anaplastic thyroid cancer, salivary-duct cancer, ovarian cancer, and colorectal cancer; not much confidence can be placed on these results.
This study is a proof-of-concept that ushers in an era of molecular medicine. Though the results aren’t enough to yield an approval, this is a good starting point.