Virtual Library

Start Your Search

Jun Ma



Author of

  • +

    P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)

    • Event: WCLC 2020
    • Type: Posters
    • Track: Targeted Therapy - Clinically Focused
    • Presentations: 1
    • Moderators:
    • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
    • +

      P76.88 - Real-World Data of Osimertinib in Patients with Metastatic EGFRm+ NSCLC who Progressed on First-Line EGFR TKIs (ID 3646)

      00:00 - 00:00  |  Presenting Author(s): Jun Ma

      • Abstract
      • Slides

      Introduction

      Osimertinib is a third-generation epidermal-growth-factor-receptor tyrosine kinase inhibitor (EGFR-TKI) approved for use in EGFR-mutant lung cancer. We examined its performance in the 2nd/subsequent line setting after resistance to 1st/2nd generation EGFR-TKI.

      Methods

      We reviewed n=202 patients who received Osimertinib from July 2015 to July 2018 in the 2nd/subsequent line after progression on prior EGFR-TKI. Clinical data including patient characteristics, primary EGFR mutation, T790M mutation status, presence of baseline brain metastases (BM), first-line EGFR-TKI use and survival outcomes were retrospectively analyzed.

      Results

      Complete data from 193 patients was analyzed. Median age at diagnosis was 63 years (IQR

      55-70), 59.6% patients were females, 79.8% never-smokers, 79.3% ECOG 0-1 at start of osimertinib. Majority had EGFR exon 19 (60.6%) and exon 21 (32.1%) mutations at diagnosis. At resistance, T790M mutation was positive in 151 (78.2%) patients: 96/193 (49.2%) tumour samples and 63/193 (32.6%) plasma samples, negative in 20 (10.4%) and unknown in 22 (11.4)%. 100 (51.8%) patients received osimertinib as 2nd line, and the rest in 3rd/subsequent line. 144 (75%) received first-line gefitinib or erlotinib (1G-TKI), 47 (24%) afatinib and 2 (1%) others. Baseline BM was present in 55/192 (28.5%) patients, 37/55 (67.3%) had whole brain radiotherapy (WBRT). Baseline BM were significantly more common in the afatinib group compared to 1G-TKI group (46.8% vs 22.9%, p=0.002).

      After median follow up of 37 (95% CI 31.8-41.6) months, median progression-free survival (PFS) was 10.3 (95% CI 8.64-11.50) months and median overall survival (OS) 20 (95% CI 15.61-23.13) months. PFS was 6.3 months for those treated with prior afatinib vs 10.5 months in those who received 1G-TKI (HR 1.57, p=0.01). OS in T790M+ patients was 22.6 months vs 7.9 months in T790M-negative patients (HR 0.43, p=0.001), and PFS was 11.2 months vs 3.1 months respectively (HR 0.52, p=0.01). PFS for second-line use of osimertinib was 10.0 (95% CI 6.34-12.29) months and 10.3 (95% CI 8.05-14.03) months for third-line/beyond (p=0.3); OS was 20.5 (95% CI 15.18-23.89) and 18.7 (95% CI 14.13-23.75) months, respectively (p=0.7). Tumour T790M-positivity was associated with longer PFS (p=0.007) and OS (p=0.01) than tumour T790M-negative patients, but significance was not seen with plasma T790M-positivity.

      Physician-assessed overall response rate to osimertinib was 43% (95% CI 35.9-50.3): 48.3% in T790M+ vs 20% in T790M-negative patients. Duration of response was 11.1 (95% CI 8.28-13.67) months in T790M-positive patients.

      By multivariable analysis (MVA), ECOG ≥2 (HR 2.53, p<0.001) was associated with shorter OS, and presence of T790M+ with longer OS (HR 0.50, p=0.008). Presence of T790M+ was significantly associated with longer PFS compared to T790M-negative (HR 0.57, p=0.03). ECOG ≥2 (HR 2.10, p<0.001) and first-line afatinib use (HR 1.58, p=0.009) compared to 1G-TKI, were significantly associated with shorter PFS by MVA.

      Conclusion

      In our cohort, we confirmed that osimertinib is effective even beyond second-line for advanced EGFRm+ NSCLC for T790M+ patients. The shorter PFS in patients who received first-line Afatinib compared to 1G-TKI may be explained by significantly higher proportion of baseline BM in this group. EGFR T790M-negative disease at resistance remain an unmet treatment need.

      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.