Targeted Therapies

Monoclonal antibodies (MAbs) are antibodies produced in a laboratory instead of by the body’s immune system. They can be designed to attack cancer cells. When injected into the body, MAbs attach themselves to receptors on the surface of cancer cells and may prevent the cells from growing, serve as markers so the immune system can find and attack the cells, or make the cells more sensitive to chemotherapy. Sometimes MAbs are attached to drugs, radioactive material, or toxins because MAbs can deliver those agents to cancer cells, reducing damage to normal cells.

MAbs have been approved to treat many types of cancer, including lymphomas and lung, colorectal, and breast cancer, and MAbs are increasingly being studied and approved as first-line treatments. For example, trastuzumab (Herceptin) was approved in 2006 for patients with early-stage breast cancers that make too much of a protein called HER-2. Trastuzumab already had been approved for treating advanced (metastatic) HER-2-positive breast cancer. HER-2-positive tumors tend to grow more aggressively and are more likely to recur than tumors that don’t overproduce HER-2. Another MAb, rituximab (Rituxan), was approved in 2006 for the first-line treatment of certain types of non-Hodgkin’s lymphoma.

Clinical trials may lead to more approvals of MAbs as first-line treatments. For example, in 2007 a phase III clinical trial with patients who have advanced colorectal cancer found that the addition of the MAb cetuximab (Erbitux) to a standard first-line chemotherapy combination cut the risk of further cancer growth or spread by 15 percent. It also increased the number of patients able to undergo surgery to remove their tumors.
 

By interfering with angiogenesis — the formation and development of new blood vessels — these targeted treatments make it difficult for cancer tumors to grow and spread. Two angiogenesis inhibitors added recently to the cancer treatment arsenal are sunitinib (Sutent), approved in 2006 for kidney cancer and gastrointestinal stromal tumors (GIST), and sorafenib (Nexavar), approved in 2005 for kidney cancer. In 2007, an additional study of sorafenib in a phase III clinical trial involving patients with hepatocellular carcinoma, the most common liver cancer, yielded encouraging results: Those who received sorafenib lived about 44 percent longer than patients who didn’t receive the drug, and time to cancer progression also improved.

Another major advance in 2007 was a phase III clinical study involving the angiogenesis inhibitor bevacizumab (Avastin), which also is a monoclonal antibody. The trial showed that adding bevacizumab to an older kidney cancer drug as a first-line treatment for advanced kidney cancer almost doubled progression-free survival, which is the length of time during and after treatment in which the cancer does not grow. Bevacizumab also is used to treat metastatic colorectal cancer and non-small cell lung cancers.
 

These therapies work by hindering the action of enzymes, which play a role in the chemical messages necessary for the cell to grow and develop. An example is erlotinib (Tarceva), approved in 2004, for patients with non-small cell lung cancer who have been treated with another chemotherapy medication and not gotten better. In 2005, it was approved for patients with pancreatic cancer.