Benefits of some cancer drugs exaggerated because trials were stopped early

Apr 9 2008

Italian scientists say the benefits of some cancer drugs may be exaggerated as a rising number of trials are stopped early.

The scientists say drugs hailed as breakthrough treatments for cancer may be less effective and cause more harm than suspected.

The researchers from the Mario Negri Institute for Pharmacological Research in Milan, say data from many of the recent cases had been used to get drug licenses before the long-term impacts were known.

The research team conducted an analysis of 25 drug trials, including some for the breast cancer therapy Herceptin, that were stopped early over a ten year period between 1997 and 2007.

The drugs tested in the trials that were stopped early include some of the biggest new discoveries in cancer therapy, and include Herceptin (trastuzumab) for breast cancer, Avastin (bevacizumab) for bowel and kidney cancer, Campto (irinotecan) for lung and bowel cancer, Sutent (sunitinib) for kidney and gastrointestinal cancer, Nexavar (sorafenib) for kidney cancer, and TaxolCarbo (carboplatin) for ovarian and lung cancer.

Their report shows that of the 25 trials randomly chosen, 14 had been stopped in the past three years, of these, 11 were used to support applications for marketing authorisation from regulators in Europe or the U.S.

Lead researcher Dr. Giovanni Aplone says when a trial is stopped early data on effectiveness and potential side-effects can be missed.

Dr. Aplone suspects the increase in early conclusions to trials suggests that drug firms use good interim results to get their products to market more quickly.

While Dr. Aplone admits that hard evidence to back this claim is scant, he says an in-built bias exists in the system because trials were often only stopped early because the results were positive, when this could just be a "random high", while, those that did not show such positive results were given more time to prove their worth.

The researchers found that the average study duration was 30 months, when the long-term impact could only be judged over years and some trials only enrolled less than 40% of the total patients originally planned.

The researchers say regulators need to take into account the impact of stopping a trial early when making decisions about licenses and make more use of independent monitoring committees to verify trial data.

Currently only the largest trials adopt this approach.

Experts agree the issue is a problem which is not confined to cancer drugs but all kinds of treatment.

They say while there is a dilemma when results are positive because those patients involved in the studies, but not receiving the therapies, could lose out, proof beyond reasonable doubt is needed to stop a trial early.

Dr. Apolone says it could take years for the long-term benefits or dangerous side-effects of a drug to become evident and the main worry was that early stopping exaggerated the beneficial effects.

Drug companies however insist that finishing trials early saves lives.

The report appears in the Annals of Oncology.