Ultimate Fate of Oncology Drugs Approved by the US Food and Drug Administration Without a Randomized Trial

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Ultimate Fate of Oncology Drugs Approved by the US Food and Drug Administration

Without a Randomized Trial

Apostolia- Tsimberidou, Fadi Braiteh, J. , Razelle Kurzrock

From the Phase I Program, Department of Investigational Cancer Therapeutics, and

Thoracic, Head and Neck Medical Oncology, The University of Texas M. D.

Cancer Center, Houston, TX.

Corresponding author: Apostolia- Tsimberidou, MD, PhD, The University of

Texas M. D. Cancer Center, Department of Investigational Cancer

Therapeutics, Unit 455, 1515 Holcombe Blvd, Houston, TX 77030, e-mail:

atsimber@... .

Purpose To approve a new anticancer drug, the US Food and Drug Administration

often requires randomized trials. However, several oncology drugs have been

approved on the basis of objective end points without a randomized trial. We

reviewed the long-term safety and efficacy of such agents.

Methods We searched the Web site of the US Food and Drug Administration's Center

for Drug Evaluation and Research and MEDLINE for initial applications of

investigational anticancer drugs from 1973 through 2006.

Results Overall, 68 oncology drugs, excluding hormone therapy and supportive

care, were approved, including 31 without a randomized trial. For these 31

drugs, a median of two clinical trials (range, one to seven) and 79 patients

(range, 40 to 413) were used per approval. Objective response was the most

common end point used for approval; median response rate was 33% (range, 11% to

90%). Thirty drugs are still fully approved. United States marketing

authorization for one drug, gefitinib (an epidermal growth factor receptor

[EGFR] inhibitor), was rescinded after a randomized trial showed no survival

improvement; however, this trial was performed in unselected patients, and it

was subsequently demonstrated that patients with EGFR mutation are more likely

to respond. Nineteen of the 31 drugs have additional uses (per National

Comprehensive Cancer Network or National Cancer Institute Physician Data Query

guidelines), and subsequent formal US Food and Drug Administration approvals

were obtained for 11 of these (range, one to 18 new indications). No drug has

demonstrated safety concerns.

Conclusion Nonrandomized clinical trials with definitive end points can yield US

Food and Drug Administration approvals, and these drugs have a reassuring record

of long-term safety and efficacy.

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