By Andrew Ciupek, Ph.D., Manager, Clinical Research, GO2 for Lung Cancer

Approximately 30% of Non-Small Cell Lung Cancers (NSCLC) have an EGFR mutation. For these patients EGFR targeted therapy has greatly increased survival. Tagrisso (osimertinib) has become the drug of choice for EGFR+ (positive) NSCLC treatment after the FLAURA clinical trial showed that patients who got Tarceva as their first treatment had longer survival than patients who received other EGFR targeted therapies. However, Tagrisso resistance remains a problem with a significant group of EGFR+ patients having progression after receiving Tagrisso for a while. Although we do not yet know the best treatments for every patient who develops Tagrisso resistance, several different options are being tried by doctors and looked at in clinical trials.

A few examples include:

1) Using other approved EGFR targeted therapies

Sometimes doctors may recommend the use of other EGFR targeted therapies by themselves or in combination with Tagrisso depending on what specific EGFR mutations are present in the cancer when progression happens. For instance, the T790M mutation is associated with having a good response to Tagrisso and either an exon 19 deletion or an L858R mutation is associated with a having a good response to several EGFR targeted therapies such as Gilotrif (afatinib). If the cancer has both mutations some doctors may recommend a combination of Tagrisso and Gilotrif. However, some EGFR mutations, such as C797S, are associated with poor response to Tagrisso and other targeted therapies. If the cancer has a mutation like C797S, doctors may not recommend using one of the already approved EGFR targeted therapies. In order to find out what EGFR mutations are present and what drugs may be an option it is important to ask about comprehensive biomarker testing if you are having progression on your current therapy. (See the article in this issue titled How Biomarker Testing Affects Patients for more information on comprehensive biomarker testing and when it can play a role in treatment).

2) Using other targeted therapies

Recent clinical research has shown that some EGFR+ patients who develop Tagrisso resistance also may develop a new mutation in their tumor that may play a role in Tagrisso no longer working. There are several clinical trials trying to see if giving a targeted therapy for a new mutation that develops after Tagrisso stops working will help patients. For instance, the ORCHARD clinical trial is testing several targeted therapies for different mutations that may develop after progression on Tagrisso as a first treatment. Patients are matched to a targeted therapy based on the results of comprehensive biomarker testing done when they enter the trial. Another example is the INSIGHT 2 clinical trial that is looking at giving the MET targeted therapy drug called tepotinib to EGFR+ patients who have progressed on Tagrisso and have also developed a new mutation called a MET amplification. It is important to ask about comprehensive biomarker testing if you are experiencing progression to see if any new mutations may be present that could match with a clinical trial.

3) Using immunotherapy combinations

Early clinical trials with immunotherapies showed that they did not work as well as targeted therapies given as a first treatment for EGFR+ NSCLC. However, the IMpower150 clinical trial has provided evidence that some EGFR+ patients who have progression on EGFR targeted therapies, like Tagrisso, may benefit from immunotherapy combinations with other drugs. In this trial some of these patients responded to a combination of the immunotherapy Tecentriq (atezolizumab), chemotherapy, and a drug called Avastin (bevacizumab). Since IMpower150, some doctors may recommend an immunotherapy combination treatment for certain patients that have progression after receiving Tagrisso.

If you are an EGFR+ NSCLC patient experiencing progression after Tagrisso treatment talking with your oncologist about these options and others can help you find the best next step. You can also speak to one of the LungMATCH specialists at GO2 for Lung Cancer for more information on treatment and/or clinical trial options. To speak with a LungMATCH specialist call us at 1-800-298-2436 or email us at support@go2.org.