Many genetic mutations have been identified in lung cancer tumors, and the mutations that have FDA-approved targeted therapies are increasing. All metastatic adenocarcinoma tumors should be tested for EGFR and ALK, as should some squamous tumors. Even though we only have a few FDA-approved targeted therapies, many more mutations have been identified and are being studied in ongoing clinical trials for use in these other mutations.
a. EGFR MUTATION POSITIVE
The EGFR receptor targets in a lung cancer cell can make it sensitive to what are known as “EGFRinhibitors.” A patient’s tumor is referred to as “EGFR mutation positive” if it has this gene alteration in its cells. Examples of EGFR inhibitors are the drugs Tarceva® and Gilogrif®.
When a patient has an “EGFR mutation positive” tumor, his/her cancer can be highly sensitive to treatment with drugs like Tarceva® and Gilogrif®. Side effects of this treatment may include diarrhea and rash, although these side effects are usually manageable. In this situation, patients can actually receive Tarceva® and Gilogrif® before receiving any chemotherapy.
This treatment can cause the cancer to remain 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® and Gilogrif® even though they are “EGFR mutation positive.” For these patients’ lung cancers (as for those patients whose tumor is resistant to Tarceva® or Gilogrif®) there are new “next generation” inhibitors being developed.
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 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 using tumor samples but the most frequent method is to use a test known by the acronym “FISH.”
“ALK Mutation Positive”
Tumors with this mutation are likely to be highly sensitive to new drugs like Xalkori® and ZyKadia®, which are “ALK inhibitors.” Most patients report only mild side effects. New next generation ALK inhibitors are available in clinical trials and may be even more effective. They may even work in tumors that have become resistant, meaning they initially responded to Xalkori® or ZyKadia®, but have stopped responding.
There are other mutations 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 may also wish to consider participating in clinical trials for which they are qualified, as all new drugs must go through this standard approval process.