Therapy Finder Advisor
Director of the Thoracic Oncology Program
Professor, University of Chicago
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.
|Drug||Other names||Drug Target||Manufacturer||Status|
|Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs): A better mousetrap? A review of the clinical evidence.||Ou Sai-Hong Ignatius, Crit. Rev. Oncol. Hematol. Sep 2012;83(3):407-21.|
|New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer.||Oxnard Geoffrey R, Clin. Cancer Res. Sep 2011;17(17):5530-7.|
|Targeting epidermal growth factor receptor: central signaling kinase in lung cancer.||Yoshida Takeshi, Biochem. Pharmacol. Sep 2010;80(5):613-23.|
|EGFR T790M mutation: a double role in lung cancer cell survival?||Suda Kenichi, J Thorac Oncol. Jan 2009;4(1):1-4.|
|Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib.||Kosaka Takayuki, Clin. Cancer Res. Oct 2006;12(19):5764-9.|