New melanoma drug illustrates shift in cancer research as treatments get personal

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Results from a large international phase III clinical trial conducted at 104 centers in 12 countries brings exciting news to some melanoma patients, and to medical progress as well. At the annual American Society of Clinical Oncology meeting, researchers announced that treatment of melanoma with a therapy that targets a specific genetic mutation had an “astounding” 63 percent reduction in the risk of death in patients with the BRAF V600 mutation, which is found in about 90 percent of melanomas.

In their study published in the New England Journal of Medicine, Dr. Paul B. Chapman of Memorial Sloan-Kettering Cancer Center in New York City and colleagues randomized 675 patients whose cancers had the BRAF V600 mutation, administering either oral vemurafenib (developed by Roche Holding AG and Daiichi Sankyo’s Plexxikon unit) or intravenous dacarbazine, the current standard of care. Patients treated with the experimental drug showed a 20 percent absolute difference in six-month overall survival compared to the dacarbazine treatment group. In addition, median progression-free survival was 5.3 months with vemurafenib, compared to 1.6 months for dacarbazine.

“Unlike recently introduced ‘miracle’ cancer therapies, we’re not talking about simply a one-to-three month benefit here,” says ACSH’s Dr. Gilbert Ross. “This is a substantial increase in progression-free survival since patients with disseminated melanoma have about a one-year survival rate. Now, many of them will become candidates for this marvelously effective drug.”

The new drug, which targets a specific molecular pathway, marks a paradigm shift in cancer research and treatment: this new model uses genetic information to match drugs with specific tumor mutations. In an article for The Wall Street Journal, Ron Winslow investigates this burgeoning area of research, citing examples where rival pharmaceutical companies are actually working together to combine targeted therapies with more conventional ones in order to increase efficacy.

Making the transition to targeted therapies does come with its own set of challenges, however. Companies that develop such drugs must also create a valid companion diagnostic test in order to identify candidates for the treatment, which is reviewed separately by the FDA. But Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, says the agency is working to change their regulatory policies in order to accommodate these recent advances: “We are on the tipping point of a whole new game in how we develop drugs [for cancer],” she stated at a recent cancer symposium in New York.

In addition to regulatory changes, targeted therapies also become a question of cost. Both Massachusetts General Hospital and the MD Anderson Cancer Center now routinely analyze the genetic profile of every patient’s tumor. “If you look at this from the long term point of view,” says Dr. Ross, “discovering tumors that are responsive to specific therapies will actually save more lives and money down the road. It may be a huge investment now,” he observes, “but it opens the door for us to learn more about specific molecular pathways and how they work so we can come up with treatments for cancer as well as other conditions.”