In the Pipeline

Prospective clinical studies that evaluate off-label uses of approved oncology drugs for advanced cancers should include patients in community settings and, whenever possible, should use actual survival as the primary outcome, according to recommendations published online Jan. 17 in the Journal of Clinical Oncology.

These and other proposed recommendations are outlined in a document intended "to guide the design of future prospective trials for off-label use of oncology drugs," wrote C. Daniel Mullins, Ph.D., professor of pharmacoeconomics at the University of Maryland, School of Pharmacy, Baltimore, and his coauthors, in the paper, published online (doi:10.1200/JCO.2011.35.5198). The recommendations "address the needs of patients and their clinical providers, compendia, payers, and policy makers," and focus on "the design of clinical studies to support evidence-based clinical and health policy decision making, but do not focus on changing the FDA-approved label of these drugs or resulting in approvals of the indications."

Referring to the "pervasive" use of oncology drugs for nonapproved indications, the authors noted that, in 2005, 50%-75% of cancer drugs were being used off label, an increase from previous years, but clinical evidence was available to support use of the drug for only about 27% of the off-label indications. Sources oncologists turn to when prescribing off-label treatments for patients include Food and Drug Administration–approved drug labels, medical literature, anecdotal information from colleagues, and continuing education programs, which are useful, but "reflect evidentiary gap that make it difficult for end users to gain information sufficient to make informed treatment decisions," they said.

The recommendations are based on the proceedings of a November 2009 meeting hosted by the Center for Medical Technology Policy (CMTP), with input from oncologists, drug manufacturers, the FDA, the National Cancer Institute, Centers for Medicare and Medicaid Services, public and private payers, and other stakeholders. The recommendations apply to studies of drugs for late-stage cancers, "in which there are hypothesized survival benefits for the drugs being examined in new indications," and are most likely relevant to patients who have been pretreated and have gone beyond first-line treatments. (The CMTP is a private, nonprofit organization, which "serves as a neutral forum to promote discussion and development strategies that improve the quality of clinical research for health care decision making," according to its website. (The founder and director, Dr. Sean Tunis, is a coauthor of the paper.)

"In oncology, more so than in any other area of medicine, drugs are used outside of FDA-labeled indications," Dr. Mullins said in an interview. In some cases, there is good evidence of the drug’s net health benefit for the indication that has not resulted in approval for that indication or a label change. "But oftentimes, there is very limited evidence, so physicians have to make decisions and talk with patients about important decisions that affect their lives," without adequate evidence, he noted.

To address this gap, the group provided recommendations about the conduct of clinical trials of off-label indications so that the study of a treatment and the data collected in the postapproval setting parallel what takes place in the "preapproval process for a drug being reviewed for an indication being considered for [FDA] approval, where the data are more consistent," said Dr. Mullins, who is also with the School of Pharmacy’s Center of Drugs and Public Policy."Our goal is to help patients and their physicians make better informed decisions" by making more consistent data available, so that if, for example, two drug options have been studied in similar trials, "you can compare them more readily," he added.

01/18/12  

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FROM THE JOURNAL OF CLINICAL ONCOLOGY

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