Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Therapy for EGFR tyrosine kinase inhibitor-resistant NSCLC with afocus on the T790M-resistant mutation

Therapy for EGFR tyrosine kinase inhibitor-resistant NSCLC with afocus on the T790M-resistant... The molecular characterisation of nonsquamous lung cancer has now become a standard procedure. In addition to the rare EML4-ALK and ROS-1 mutations, the detection of an epidermal growth factor receptor (EGFR) mutation has become a crucial factor in the selection of an optimal targeted therapy. Deletion of exon 19 and the L858R point mutation account for approximately 90 % of activating EGFR mutations and patients with these mutations are highly sensitive to treatment with EGFR tyrosine kinase inhibitors (EGFR TKIs). First-generation EGFR TKIs (gefitinib, erlotinib) reversibly inhibit the EGFR tyrosine kinase, while second-generation EGFR TKIs (afatinib, dacomitinib) are irreversible EGFR TKIs. However, despite an often excellent initial response to treatment with first- or second-generation EGFR TKIs, patients eventually develop drug resistance after approximately 9–12 months of treatment. T790M-targeting third-generation EGFR TKIs as osimertinib and rociletinib have shown high response rates of about 60 % in EGFR T790M-positive pretreated patients with a favourable toxicity profile. Unfortunately, patients eventually developed resistance to these drugs after approximately 10 months and the third-generation EGF R Cys797S mutation was recently reported to be a potential mechanism of resistance to third-EGFR TKIs. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png memo - Magazine of European Medical Oncology Springer Journals

Therapy for EGFR tyrosine kinase inhibitor-resistant NSCLC with afocus on the T790M-resistant mutation

Download PDF
4 pages

Loading next page...
 
/lp/springer-journals/therapy-for-egfr-tyrosine-kinase-inhibitor-resistant-nsclc-with-afocus-N1bi0fG6Hi
Publisher
Springer Journals
Copyright
Copyright © 2016 by Springer-Verlag Wien
Subject
Medicine & Public Health; Oncology; Medicine/Public Health, general
ISSN
1865-5041
eISSN
1865-5076
DOI
10.1007/s12254-016-0288-y
Publisher site
See Article on Publisher Site

Abstract

The molecular characterisation of nonsquamous lung cancer has now become a standard procedure. In addition to the rare EML4-ALK and ROS-1 mutations, the detection of an epidermal growth factor receptor (EGFR) mutation has become a crucial factor in the selection of an optimal targeted therapy. Deletion of exon 19 and the L858R point mutation account for approximately 90 % of activating EGFR mutations and patients with these mutations are highly sensitive to treatment with EGFR tyrosine kinase inhibitors (EGFR TKIs). First-generation EGFR TKIs (gefitinib, erlotinib) reversibly inhibit the EGFR tyrosine kinase, while second-generation EGFR TKIs (afatinib, dacomitinib) are irreversible EGFR TKIs. However, despite an often excellent initial response to treatment with first- or second-generation EGFR TKIs, patients eventually develop drug resistance after approximately 9–12 months of treatment. T790M-targeting third-generation EGFR TKIs as osimertinib and rociletinib have shown high response rates of about 60 % in EGFR T790M-positive pretreated patients with a favourable toxicity profile. Unfortunately, patients eventually developed resistance to these drugs after approximately 10 months and the third-generation EGF R Cys797S mutation was recently reported to be a potential mechanism of resistance to third-EGFR TKIs.

Journal

memo - Magazine of European Medical Oncology – Springer Journals

Published: Oct 11, 2016

References

  • Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer
    Scagliotti, G; Parikh, P; Pawel, J; Biesma, B; Vansteenkiste, J
  • Treatment outcomes by tumor histology in Eastern Cooperative Group Study E4599 of bevacizumab with paclitaxel/carboplatin for advanced non-small cell lung cancer
    Sandler, A; Yi, J; Dahlberg, S; Kolb, MM; Wang, L; Hambleton, J; Schiller, J
  • Predictive and prognostic impact of epidermal growth factor receptor mutation in non-small-cell lung cancer patients treated with gefitinib
    Han, S; Kim, T; Hwang, P; Jeong, S; Kim, J; Choi, I
  • Molekularpathologie des Lungenkarzinoms „State of the art“ 2014
    Warth, A; Endris, V; Penzel, R; Weichert, W
  • Molekulardiagnostik des nichtkleinzelligen Lungenkarzinoms. Neue Marker und Technologien
    Warth, A; Endris, V; Kriegsmann, M; Stenzinger, A; Penzel, R; Pfarr, N; Weichert, W
  • Generations of epidermal growth factor receptor Tyrosine Kinase inhibitors: perils and progress
    Castellanos, E; Horn, L
  • Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer
    Wang, S; Cang, S; Liu, D
  • Attacking a moving target: understanding resistance and managing progression in EGFR-positive lung cancer patients treated with Tyrosine Kinase inhibitors
    Levy, B; Rao, P; Becker, D; Becker, K
  • Mechanisms of resistance to EGFR tyrosine kinase inhibitors
    Huang, L; Fu, L
  • Delay of treatment change after objective progression on first-line erlotinib in epidermal growth factor receptor-mutant lung cancer
    Lo, P; Dahlberg, S; Nishino, M; Johnson, B; Sequist, L; Jackman, D
  • Local ablative therapy of oligoprogressive disease prolongs disease control by tyrosine kinase inhibitors in oncogene-addicted non-small-cell lung cancer
    Weickhardt, A; Scheier, B; Burke, J; Gan, G; Lu, X; Bunn, P
  • Local therapy with continued EGFR tyrosine kinase inhibitor therapy as a treatment strategy in EGFR-mutant advanced lung cancers that have developed acquired resistance to EGFR tyrosine kinase inhibitors
    Yu, H; Sima, C; Huang, J; Solomon, S; Rimner, A; Paik, P
  • Impact of continuing first-line EGFR Tyrosine Kinase inhibitor therapy beyond RECIST disease progression in patients with advanced EGFR-mutated non-small-cell lung cancer (NSCLC): retrospective GFPC 04-13 study
    Auliac, J; Fournier, C; Audigier, V; Perol, M; Bizieux, A; Vinas, F
  • Chemotherapy with Erlotinib or chemotherapy alone in advanced non-small cell lung cancer with acquired resistance to EGFR tyrosine kinase inhibitors
    Goldberg, S; Oxnard, G; Digumarthy, S; Muzikansky, A; Jackman, D; Lennes, I; Sequist, V
  • Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial
    Soria, J; Wu, Y; Nakagawa, K; Kim, S; Yang, J; Ahn, M
  • Phase III multinational, randomized, double-blind, placebo-controlled study of Tivantinib (ARQ 197) plus Erlotinib versus Erlotinib alone in previously treated patients with locally advanced or metastatic nonsquamous non-small-cell lung cancer
    Scagliotti, G; Pawel, J; Novello, S; Ramlau, R; Favaretto, A; Barlesi, F
  • Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung cancer
    Borghaei, H; Paz-Ares, L; Horn, L; Spigel, D; Steins, M; Ready, N
  • Next-generation sequencing of tyrosine kinase inhibitor-resistant non-small-cell lung cancers in patients harboring epidermal growth factor-activating mutations
    Masago, K; Fujita, S; Muraki, M; Hata, A; Okuda, C; Otsuka, K
  • AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer
    Jänne, P; Yang, J; Kim, D; Planchard, D; Ohe, Y; Ramalingam, S
  • Rociletinib in EGFR-mutated non-small-cell lung cancer
    Sequist, L; Soria, J; Goldman, J; Wakelee, H; Gadgeel, S; Varga, A
  • Whacking a mole-cule: clinical activity and mechanisms of resistance to third generation EGFR inhibitors in EGFR mutated lung cancers with EGFR-T790M
    Costa, D; Kobayashi, S
  • First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer
    Greenhalgh, J; Dwan, K; Boland, A; Bates, V; Vecchio, F