What Is an “Off Label” Cancer Drug?

Sometimes the term “off label” comes up in discussions of cancer drugs.  What does “off label” mean?

All prescription drugs sold in the USA have been approved for use by the U.S. Food and Drug Administration (FDA).  After a drug is approved by the FDA, it sometimes is used for different purposes or in different populations.  That is “off label” use of a drug.  As WebMD explains, it’s perfectly legal. Per the National Cancer Institute’s definition, off label is “the legal use of a prescription drug to treat a disease or condition for which the drug has not been approved by the U.S. Food and Drug Administration.”

Consumer Reports states off label drug prescription is actually very common.  More than one in five outpatient prescriptions today are written off label.  For instance, Neurontin (also known as gabapentin) was originally approved to treat seizures.  It is now also used to treat nerve pain and neuropathy – an off label use.  However, one trusts that one’s doctor will only prescribe a drug with good evidence that drug is useful for the patient’s disease or condition.

Two types of off label use occur. The first type is when a drug is used to treat the approved disease, but used in a manner different than stated in the FDA approval.  For instance, use of the antidepressant Zoloft is off label in children (Zoloft is FDA approved for adults only); taking a drug in a larger dose or on a different schedule than that approved by the FDA is also off label. The second type of off label use is when a drug is used to treat a condition or disease different than that for which the drug was originally approved.

Cancer drugs are sometimes used off label to treat metastatic patients who have exhausted traditional treatment options, but only if evidence indicates the drug might be effective against the patient’s particular cancer situation.  For example, crizotinib (Xalkori) was approved by the FDA only for non small cell lung cancer (NSCLC) patients whose tumors tested positive for the ALK translocation (a type of mutation in a specific gene called ALK).  In addition, the approval stated the patient’s ALK-positive (ALK+) status had to be determined by a specific molecular test.  Prescribing Xalkori for patients who test ALK+ using a different type of test (genomic profiling) is an off label use, because the patients weren’t tested with the specific test named in the FDA approval.  This is not a big deal, because research indicates both tests identify ALK+ tissue with high accuracy.

Xalkori is also legally prescribed for a different disease: ROS1+ lung cancer in patients (like me). ROS1 is a different tumor mutation than ALK, but has a similar structure–technically, ROS1+ NSCLC is a different disease than ALK+ NSCLC. This is an off-label use, because Xalkori has not been approved for treating ROS1+ lung cancer.  Xalkori for ROS1+ lung cancer has been in clinical trials for over two years, with a goal of someday obtaining FDA approval (this is the clinical trial in which I am enrolled). Strong evidence from this clinical trial indicates Xalkori has a high response rate in ROS1+ lung cancer patients, so oncologists are now prescribing Xalkori for this use even though it’s not approved by the FDA for that purpose.

Even a drug that’s approved to treat a particular cancer can be used to treat that cancer in off-label ways. Examples are when a drug normally approved for first line treatment is used for maintenance, or when the dosing interval differs from the schedule called out in the FDA approval.  A friend who has metastatic lung cancer could not tolerate the standard combination chemotherapy for lung cancer because he couldn’t have a platinum drug.  He wanted to have Gemzar, a relatively well-tolerated chemo, off label as a single agent (Gemzar’s FDA approval says it must be used with a platinum drug). After consulting several different oncologists, all of whom wanted to put him on hospice, he found an oncologist willing to give him Gemzar off label as a single agent.  My friend was stable on Gemzar for over two years.

As genomic testing identifies more mutations in different types of cancer tumors, drugs that are FDA approved for one type of cancer – say, a BRAF inhibitor for melanoma– might be tried in a BRAF+ lung cancer patient.  Or, an oncologist might prescribe a cancer drug off label after a functional profiling assay indicates a drug approved for a different cancer is effective against a patient’s tumor tissue. Until FDA approval is given for the drug to be used in a different cancer, this is considered an off label use. However, it could also be a life-saving use for the patient.

“As a cancer patient, it’s always a good idea to ask your oncologist what evidence he has for using a drug off label to treat your cancer. Most oncologists will cite results from early research or a clinical trial. If they don’t have such evidence, ask LOTS of questions. You as the patient are ultimately the one assuming the risk of an off label drug.”

Assuming one has an up-to-date and responsible oncologist, a cancer patient’s primary concerns regarding an off label cancer drug are usually side effects, and whether their insurance will cover a non-approved use of that drug. Sometimes insurance companies will not cover a pricey drug used off label.  When oncologists started prescribing Xalkori for ROS1+ lung cancer outside of clinical trials, some insurance companies refused to cover the expensive drug (around US $10,000 per month) because it was not FDA approved for that type of cancer.  However, I’m hearing more ROS1+ LC patients say their insurance is covering Xalkori even without FDA approval. Insurance companies are learning to adapt to the changing molecular landscape of cancer, just as researchers, oncologists, regulators and professional organizations are.

The times they are a changin’.  Off label cancer drugs may be the new black.