by Barbara A. Brenner
Debu Tripathy is a professor of internal medicine and the Annette Simmons Distinguished Chair in Breast Cancer Research at the University of Texas Southwestern Medical Center. Through his work in clinical research, he has come to appreciate breast cancer’s complexities, including the culture and politics of the disease. He is involved in both clinical practice and breast cancer research.
At the medical center, Tripathy sees only breast cancer patients. BCA caught up with him to ask about the off-label use of breast cancer drugs. For Tripathy, “off-label drug use” refers to using drugs for a purpose that has not been approved by the FDA. “They have not yet been subjected to randomized controlled trials in that setting,” he explains, “but there is some other evidence of the drug’s effectiveness in the intended situation, usually from smaller trials or from other diseases.”
The off-label use of drugs in a cancer setting is controversial, because patients are subjected to unknown potential side effects. Tripathy uses drugs off-label only if he believes that doing so will have a reasonable chance of helping his patients. When he does, he explains why the use is off-label, what the rationale is for using it, and what the other treatment alternatives are.
The factors that influence Tripathy’s decision to use a drug off-label involve the type of evidence that is available regarding the drug, the strongest being a randomized, controlled trial comparing the drug under consideration to the standard of care, and showing that the drug actually offers an advantage to patients even if it has not yet gained FDA approval. However, even encouraging results from a trial where there is no comparison to standard therapy (termed a Phase II trial) can sometimes be compelling enough to recommend off-label use. “Safety is always a factor, and a recommendation is always made in the context of how much a treatment might help,” Tripathy says.
Once a drug has been approved by the FDA, Tripathy is much more likely to use it with his patients. However, he knows from his own clinical practice that the data from clinical trials do not always give all of the information about a treatment’s side effects. Tripathy takes caution, based on his experience, in incorporating a new drug or diagnostic assay into his clinical practice. This is important because knowledge of the benefits and side effects of a treatment becomes evident over time. He adopts new treatment practices in stages—first offering the drug to those that he thinks will derive the greatest benefit. For example, adjuvant Herceptin was used only on higher-risk patients in the beginning. As more safety data became available, Tripathy was willing to use it on lower-risk cases, where the benefits might be smaller.
Tripathy has clear ideas about what kinds of information doctors and patients should use in deciding what treatment is appropriate. The central issue is whether the overall benefits exceed the overall risks, and he tries to individualize treatments to the best extent possible.
Tripathy also recognizes that it takes time for a patient to comprehend these concepts, noting the “numerous issues that patients deal with day to day once they’ve been diagnosed and are trying to make treatment decisions.” And he recognizes that most decisions can be made on a conditional basis—if a patient can tolerate it reasonably well, a treatment can continue. Additionally, as new risks become known, people will need to receive pertinent information so they can reconsider their decisions.
Medicare and other insurance companies will sometimes cover the costs of off-label drugs if there is early evidence of effectiveness and safety even if they’re not FDA-approved. The FDA does not regulate the off-label use of drugs. BCA is concerned about the FDA’s capacity to monitor safety once a drug has been approved. For more information, contact BCA at email@example.com.
As of press time, Tripathy has taken a new position as the president and chief executive officer of Physicians’ Education Resource in Dallas, Texas.