Supplementary Figures 1-8 from Antitumor Activity of Osimertinib, an Irreversible Mutant-Selective EGFR Tyrosine Kinase Inhibitor, in NSCLC Harboring EGFR Exon 20 Insertions

Authors:
  • NFNicolas Floc'H
    Nicolas Floc'H
  • MMMatthew J. Martin
    Matthew J. Martin
  • JRJonathan W. Riess
    Jonathan W. Riess
  • JOJonathan P. Orme
    Jonathan P. Orme
  • ASAnna D. Staniszewska
    Anna D. Staniszewska
  • LMLudovic Ménard
    Ludovic Ménard
  • MCMaria Emanuela Cuomo
    Maria Emanuela Cuomo
  • DODaniel J. O'Neill
    Daniel J. O'Neill
  • RWRichard A. Ward
    Richard A. Ward
  • MFM. Raymond V. Finlay
    M. Raymond V. Finlay
  • DMDarren McKerrecher
    Darren McKerrecher
  • MCMingshan Cheng
    Mingshan Cheng
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Abstract
Supplementary figure 1: Generation of H2073 ASV and H2073 SVD. Supplementary figure 2: H2073 parental and Ex20Ins are dependent on EGFR for survival in vitro. Supplementary figure 3: Effect of TKI on the Sytox Proliferation of H2073 wt, H2073-SVD and H2073-ASV, in vitro. Supplementary figure 4: The H2073 parental NSCLC xenograft model is sensitive to afatinib in vivo. Supplementary figure 5: Osimertinib and AZ5104 given as monotherapy induce robust inhibition of p-EGFR and relevant downstream signalling pathways. Supplementary figure 6: Osimertinib and AZ5104 as monotherapy induce a strong inhibition of the level of pEGFR and the downstream signalling pathways. Supplementary figure 7: Osimertinib, AZ5104, afatinib and erlotinib are well tolerated at the dose explored in the PDX models and AZ5104 induce significant tumor growth inhibition in the LU0387 model when dosed at 50 mg/kg. Supplementary figure 8: Osimertinib, afatinib and erlotinib robustly inhibit pEGFR; however, select proteins representing downstream signalling pathways (pAKT) have enhanced inhibition to osimertinib and pS6R remains suppressed at early timepoints compared to afatinib and erlotinib in the UC Davis PDX model harboring the V769_D770InsASV.