Virtual Library

Start Your Search

Wei Gu



Author of

  • +

    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.13-25 - Efficacy and Safety of Osimertinib in EGFR T790M-Positive Advanced NSCLC Patients with Brain Metastases (APOLLO Study) (ID 13178)

      16:45 - 18:00  |  Author(s): Wei Gu

      • Abstract
      • Slides

      Background

      Osimertinib has demonstrated promising efficacy in T790M-positive NSCLC patients with central nervous system (CNS) metastases, but there is limited data on Chinese patients. We aim to investigate the efficacy and safety of osimertinib in T790M-positive advanced NSCLC patients with brain metastases and to explore the dynamic genetic changes as well as drug penetration in CNS with paired cerebrospinal fluid (CSF) and plasma samples.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      In this single arm, multi-center, prospective trial (NCT2972333), patients with confirmed EGFR T790M positive by Cobas, advanced NSCLC with brain metastases, who had progressed following first-generation EGFR-TKI treatment, received osimertinib 80 mg qd. The primary endpoint was overall progression free survival (PFSo). Paired CSF-plasma samples were collected at baseline, 6 weeks after treatment and disease progression and analyzed by NGS.

      4c3880bb027f159e801041b1021e88e8 Result

      Thirty-eight eligible patients were enrolled and 12 paired CSF-plasma samples were collected. Baseline characteristics and efficacy results are summarized in Table 1. Median PFSo (60% maturity, 23/38) was 8.4 months (95% CI 5.8-11.0). Adverse events of grade 3 or higher were reported in 39.5% patients. Analyzed in 12 paired samples, the median CSF penetration rate of osimertinib was 31.7% (range 19.8-57.7%), with a median CSF concentration of 10.83nM (range 5.2-30.3nM). T790M mutation was detected in 83% (10/12) of plasma and 17% (2/12) of CSF samples at baseline, with a concordance rate of 8.3% (1/12). Median PFSo was prolonged in patients with EGFR sensitizing mutation clearance at week 6 compared with those with persisting EGFR mutations (not reached vs 2.83 months; HR 0.09, 95% CI 0.02-0.54; p<0.01).

      Table 1. Baseline characteristics and efficacy

      Patients characteristics N=38
      Age, median (range), years 63 (38-74)
      CNS metastases, No (%): brain metastases (BM) / leptomeningeal metastases (LM) / other 35 (92.1%) / 2 (5.3%) / 1 (2.6%)
      Histology, No (%): adenocarcinoma 38 (100%)
      EGFR mutations, No (%):
      T790M with Ex19del / L858R
      22(57.9%) /16 (42.1%)
      Sample type for T790M confirmation No (%): Blood / Tissue 27 (71.1%) / 11 (28.9%)
      Lines of anti-tumor therapy, No (%): 1 / 2 / ≥3 13 (34.2%) / 3 (7.9%) / 22 (57.9%)
      Efficacy Overall Extracranial Intracranial
      Median PFS (months, 95% CI) 8.4 (5.8, 11.0) 10.2 (7.5, 14.0) 10.9 (6.1, NA)
      Objective response rate (ORR) 42.4%(14/33) 39.4%(13/33) 71.9%(23/32)
      Disease control rate (DCR) 90.9%(30/33) 90.9%(30/33) 96.9%(31/32)
      Median Duration of Response (DoR) (months, 95% CI) 8.1 (3.4, NA) 11.1 (5.6, 11.1) 8.3 (5.8, NA)

      8eea62084ca7e541d918e823422bd82e Conclusion

      Osimertinib demonstrated promising efficacy, good blood brain barrier penetration and manageable tolerability in EGFR T790M-positive Chinese advanced NSCLC patients with brain metastases. NGS analysis revealed genetic heterogeneity between plasma and CSF samples and longitudinal genetic analysis may be beneficial to predict the efficacy of osimertinib.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.