What Targeted Therapies Are Currently Available?

Many gene mutations have been identified in lung cancer tumors, but at present only some of the mutations have FDA-approved targeted therapies that can be used in patients. The three gene mutations that are frequently tested for in lung cancer currently are EGFR, KRAS, and ALK, but we know about and test for many other mutations, and treatments are being developed for many of them. Even though we currently have only two FDA-approved targeted therapies, there are many additional compounds being tested for the other mutations.

EGFR (Epidermal Growth Factor Receptor)

a. EGFR MUTATION POSITIVE

The EGFR receptor targets in a lung cancer cell can make it sensitive to what are known as “EGFR inhibitors.”    A patient’s tumor is referred to as “EGFR mutation positive” if it has this gene alteration in its cells. An example of an EGFR inhibitor is the drug Tarceva®.

When a patient has an “EGFR mutation positive” tumor, his/her cancer can be highly sensitive to treatment with drugs like Tarceva®. Side effects of this treatment may include diarrhea and rash, although these side effects are usually easily manageable. In this situation, patients can actually receive Tarceva® before receiving any chemotherapy. This treatment can cause the cancer to stay stable or even cause the cancer to disappear for a period of time.

NOTE: There are some uncommon mutant versions of EGFR that don’t respond to treatment with Tarceva® even though they are “EGFR mutation positive.” For these patients’ lung cancers, there are new “second generation” inhibitors being developed. Ask your doctor for the latest research in this area.

b. EGFR “MUTATION NEGATIVE”

When lung cancer tumor cells do NOT have the EGFR mutation, they are called “EGFR negative” or “EGFR wildtype.” These tumors are likely to be less sensitive to drugs like Tarceva®. The drug may still inhibit cancer growth, but is less likely to cause dramatic tumor shrinkage. In this case, the drug may be used after other treatments are used first, and it is called a “second-line” or “third-line” treatment option.

ALK (Anaplastic Lymphoma Kinase)

ALK mutations are found in a smaller number of non- small cell lung cancer patients than the EGFR mutations. There are several ways to test for ALK mutations, but the most common method is to use a test known by the acronym “FISH.”

a. “ALK MUTATION POSITIVE”
Tumors with this mutation are likely to be highly sensitive to new drugs like Xalkori®, which is an “ALK inhibitor.” Most patients report only mild side effects. New “second generation” ALK inhibitors may be even more effective, and may work even in tumors that have become resistant, meaning they initially responded to Xalkori®, but have stopped responding.

b. “ALK MUTATION NEGATIVE”
These tumor cells have been found not to be sensitive to Xalkori®. However, there are several other gene mutations, such as MET and ROS, which seem to respond well to treatment with Xalkori®; ask your physician for the latest research.

KRAS (Kirsten-ras)

“KRAS mutation positive” tumors are relatively common, but there are currently no FDA-approved targeted therapies for the KRAS mutation. However, it is still useful to test for KRAS because there are multiple clinical trials showing encouraging results.

What about tumors testing negative for both EGFR and ALK mutations?

If a patient’s lung cancer tests negative for mutations in EGFR and ALK, or if his/her tumors have become resistant, a patient may be offered chemotherapy with or without targeted therapies, or s/he can be enrolled in a clinical trial for any new targeted therapy under investigation.

There are multiple other mutations (especially in genes called MET, HER2, BRAF, ROS, and RET) currently being studied as candidates for therapeutic targets, with early promising results. Patients should consider getting tested for all gene mutations, as new targeted therapies are being developed. Patients should also consider participating in clinical trials for which they are qualified, as all new drugs must go through this standard approval process.