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T790M EGFR mutation: Consider newer drugs like Gilotrif (afatinib)

You indicated that your patient's cancer has an EGFR-T790M mutation.

The T790M aberration is primarily associated with resistance to treatment with the first generation EGFR tyrosine kinase inhibitors (TKI) Tarceva (erlotinib) or Iressa (gefitinib) (Kosaka, et al. 2006). However the aberration has also been observed in some TKI-naive non-small cell lung cancers (NSCLC). In both cases, the T790M mutation is associated with significantly reduced response to first generation EGFR TKI therapy (Su KY, et al. 2012).

Several treatment modalities for addressing drug resistance due to the EGFR T790M mutation are currently being explored in clinical trials. These include 1) addition of a second targeted therapy drug to Tarceva -- such as a MET inhibitor in the case of MET amplification -- or another targeted drug that blocks another pathway potentially conferring resistance, 2) second generation tyrosine kinase inhibitors such as Gilotrif (afatinib) -- described in more detail below, 3) and Hsp90 inhibitors. All of these approaches involve investigational drugs that are currently being tested in clinical trials to determine their effectiveness alone or in combination. Your patient should consider one of the clinical trials listed below.

Drugs to consider:

Gilotrif: Gilotrif (afatinib) is a second generation EGFR inhibitor recently approved by the FDA. A large phase III clinical trial demonstrated that Gilotrif significantly increases the period of progression-free survival in comparison to the standard chemotherapy combination (pemetrexed/cisplatin) in patients with EGFR mutation-positive NSCLC (Sequist LV, et al. 2013).

dacomitinib: Dacomitinib is also a second generation EGFR inhibitor that is in clinical testing. Preliminary data suggests that dacomitinib has demonstrated 'encouraging efficacy' as first-line treatment in NSCLC patients as measured by progression-free survival (PFS) rates. Patients with EGFR mutation-positive NSCLC experienced tumor shrinkage (Mok, et al. 2011). In another study, dacomitinib demonstrated significantly improved PFS in comparison to Tarceva (erlotinib) in EGFR mutation-positive NSCLC patients (Ramalingam SS, et al. 2012).

See 'Drugs' tab below to learn about additional drugs to consider.



  • EGFR-T790M
Potentially Relevant Drug Classes

Clinical Trials

Details of your patient's condition will determine eligibility for any specific trial. We encourage shared decision-making between patients and physicians.
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The selected criteria return 46 trials.

Potentially Relevant Drugs

Drug Other names Drug Target Manufacturer Status
The information above is selected based upon the information you provided and the guidance of our editorial board. It is not necessarily comprehensive and may not reflect information that is not publicly available. The specifics of your patient's situation may suggest options not included here, or may exclude some options that we have shown.