Disease progression

The recommended first line treatment for patients with advanced non-small cell lung cancer (NSCLC), harbouring an activating or sensitising epidermal growth factor receptor (EGFR) mutation is an EGFR tyrosine kinase inhibitor (EGFR-TKI).1,2

Although patients experience a high initial response rate to first-line EGFR-TKIs, most patients with EGFR mutation-positive advanced NSCLC will progress on treatment, with a median progression-free survival range of 9.7–13.1 months.3 The most common mechanism of acquired resistance to EGFR-TKIs is the EGFR T790M mutation, which occurs with an amino acid substitution at position 790 in EGFR, from a threonine (T) to a methionine (M). Studies have shown that the incidence of the EGFR T790M mutation in tumours that have developed resistance to first-generation EGFR-TKIs (erlotinib and gefitinib) ranges from 51 to 68%.4–9

Testing for the T790M mutation is now possible using tissue and plasma samples, and methods similar to those for EGFR mutation testing at the time of primary diagnosis. Visit www.EGFR-mutation.com or www.IDLung.com for more information on EGFR mutation testing at progression.

The treatment landscape for patients with EGFR mutation-positive advanced NSCLC has now changed, with the availability of the first 3rd generation TKI approved for adult patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC (TAGRISSO [osimertinib]). TAGRISSO is an oral, selective irreversible TKI that targets both EGFR-sensitising mutations and specifically the EGFR T790M mutation while sparing wild-type EGFR. Visit www.tagrisso-global.com for further information.

References

  1. NCCN. NCCN Clinical Practice Guidelines in Oncology NSCLC (version 8.2017), 2017. Available at:
    https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed 03 July 2017.
  2. Reck M et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014; 25(Suppl 3): iii27-39.
  3. Lee CK et al. Impact of specific epidermal growth factor receptor (EGFR) mutations and clinical characteristics on outcomes after treatment with EGFR tyrosine kinase inhibitors versus chemotherapy in EGFR-mutant lung cancer: a meta-analysis. J Clin Oncol 2015; 33: 1958-1965.
  4. Arcila ME et al. Rebiopsy of lung cancer patients with acquired resistance to EGFR inhibitors and enhanced detection of the T790M mutation using a locked nucleic acid-based assay. Clin Cancer Res 2011; 17: 1169-1180.
  5. Yu HA et al. Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers. Clin Cancer Res 2013; 19: 2240-2247.
  6. Oxnard GR et al. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumours harboring the T790M mutation. Clin Cancer Res 2011; 17: 1616-1622.
  7. Sun JM et al. Clinical implications of T790M mutation in patients with acquired resistance to EGFR tyrosine kinase inhibitors. Lung Cancer 2013; 82: 294-298.
  8. Kuiper JL et al. Incidence of T790M mutation in (sequential) rebiopsies in EGFR-mutated NSCLC-patients. Lung Cancer 2014; 85: 19-24.
  9. Li W et al. T790M mutation is associated with better efficacy of treatment beyond progression with EGFR-TKI in advanced NSCLC patients. Lung Cancer 2014; 84: 295-300.