Cancer Drugs

Risks and Benefits
by Food and Drug Administration (FDA)

Few deliberations have greater bearing on human health than when the Food and Drug Administration weighs the risks and benefits of drugs designed to treat life-threatening diseases, such as cancer.

FDA physicians who specialize in treating cancer (oncologists), chemists, statisticians, microbiologists, pharmacologists, immunologists, and other experts work in concert to evaluate cancer drug data, weigh the risks and benefits, and reach a decision to approve or not approve. If the scale is tipped on the side of benefits, the drug is approved and allowed on the U.S. market.

Patients, doctors, caregivers, and family members must also weigh the risks and benefits of drugs to decide which treatments to use.

How Are Cancer Drugs Reviewed?

Under federal law, the FDA may approve a new drug for marketing in the United States if it is supported by substantial evidence of safety and effectiveness demonstrated in adequate and well-controlled studies.

The drug's manufacturer or marketer must show this evidence by submitting an application to the FDA that includes results from studies of the drug's use in people (clinical trials).

FDA experts review cancer drug applications and evaluate study results. Sometimes, they seek outside advice, calling upon a group of leading cancer specialists, clinical practitioners, and patient representatives who make up the FDA's Oncologic Drugs Advisory Committee (ODAC).

At an ODAC meeting, the pharmaceutical company presents findings from clinical trials on safety and effectiveness of the drug, and FDA staff present their assessments after reviewing the drug application. The ODAC draws conclusions intended to guide the agency in its decision to approve or not approve the drug for marketing or for a new claim.

What Makes Cancer Clinical Trials Different?

Clinical trials for cancer drugs are somewhat different from those for drugs used to treat illnesses that are less serious. For a less severe disease or condition, the commercial sponsor may show that the drug works better than an inactive substance (placebo), but generally does not have to show that it works as well or better than other drugs on the market to treat the same illness.

Studies involving cancer drugs usually do not use placebos, says Patricia Cortazar, M.D., an oncologist in the FDA's Office of Oncology Drug Products. "Because cancer is a life-threatening illness, it would not be ethical to give placebo when something better than placebo is available." In cancer trials, a new drug is usually compared to a drug or a combination of drugs that are commonly accepted and widely used to treat the same type of cancer, known as the standard of care, or standard treatment.

"The standard of care changes over time as new drugs or drug combinations that are shown to be better become available," says Cortazar.

The FDA may approve a drug for several uses (indications). If a drug is approved for one indication, it must still be shown in clinical trials to be safe and effective before the FDA will approve it for another indication.

What Do 'Safe' and 'Effective' Really Mean?

A cancer drug may be considered effective if it extends a person's life (survival), increases the probability that a person will remain alive without the disease getting worse (progression-free survival), shrinks the tumor (response rate), or relieves other symptoms. In short, FDA cancer drug reviewers ask, "Does the drug prolong life, control the disease, or relieve symptoms? And does the scientific evidence support it?"

These benefits are weighed against the risks of the drug. No drug is absolutely safe - all have some risks, or potential side effects. "Safe" means that the benefits of the drug outweigh the risks for its intended use in the population the drug is intended to treat.

Cancer drugs often contain potent ingredients that kill cancer cells. "Unfortunately, most of the drugs used to treat cancer aren't targeted," says Cortazar. "They kill the cancer cells, but at the same time, they kill healthy cells." The death of rapidly dividing healthy cells weakens the body's immune system, putting a person at risk for infections and other health problems.

Yet highly toxic effects may be considered acceptable if the benefits are important and the disease is very serious or life-threatening.

Numbers Don't Always Count

The FDA does not require a specific number of participants in a clinical trial, but trial size should be tailored to the risks acceptable to people with the disease and in consideration of the rarity of the disease. Similarly, the FDA does not require a specific number of patients to respond to a cancer drug, nor does it require the drug to extend life by a specific number of days so long as the results are convincing and clinically meaningful given the side effects of the drug and other treatment options.

"There is no hard and fast rule," says Edwin Rock, M.D., Ph.D., an oncologist in the FDA's Office of Oncology Drug Products. "The agency looks at the data and makes judgments about what's clinically significant and whether, on balance, the benefits exceed the risks." To be considered clinically significant, a finding must show real meaning for patients, such as extending their lives or making them feel better.

About the Author

www.fda.gov
FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.