Author of

• 25904

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  MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)

  • Event: WCLC 2018
  • Type: Mini Oral Abstract Session
  • Track: Targeted Therapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 13:30 - 15:00, Room 107

  • 26040

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    MA15.03 - PD-L1 Expression in Untreated EGFRm Advanced NSCLC and Response to Osimertinib and SoC EGFR-TKIs in the FLAURA Trial (ID 12989)

    13:40 - 13:45  |  Author(s): Helen Brown
    • Abstract
    • Presentation
    • Slides

    Background
    

    In the Phase III FLAURA trial (NCT02296125), osimertinib significantly improved PFS relative to SoC EGFR-TKIs (gefitinib/erlotinib) in patients with untreated Ex19del/L858R positive (EGFRm) NSCLC. EGFRm NSCLC tumors can exhibit high PD-L1 expression, an important biomarker for immunotherapy treatment decisions. The frequency and clinical relevance of exhibiting both biomarkers prior to treatment are unclear. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following EGFR-TKI treatment.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Tissue samples from 994 patients with advanced NSCLC were screened for EGFR Ex19del/L858R mutations for enrolment in FLAURA; 556 were randomized to treatment. 197 tissue-blocks from the screened population (including EGFR mutation-positive and -negative samples) were tested for PD-L1 using the SP263 (Ventana) immunohistochemical assay; positive tumour cell (TC) staining PD-L1 TC≥25% and TC≥1% thresholds were applied. PFS was investigator-assessed, per RECIST 1.1, according to PD-L1-expressers (TC≥1%) or -negatives (TC<1%) in randomized patients.

    4c3880bb027f159e801041b1021e88e8 Result
    

    193/197 blocks had sufficient tumor tissue for staining. 65/193 patients were EGFR mutation-negative. 128/193 patients were EGFR mutation-positive: 106/128 were randomized to treatment (osimertinib: 54; SoC: 52). The table presents PD-L1 expression according to EGFR mutation status. For PD-L1-expressers (TC≥1%), median PFS was 18.4 months for osimertinib and 6.9 months for SoC (HR 0.30 [95% CI 0.15, 0.60]). For PD-L1-negative patients (TC<1%), median PFS was 18.9 months for osimertinib and 10.9 months for SoC (HR 0.37 [95% CI 0.17, 0.74]).

    	PD-L1 TC≥1%, n (%)	PD-L1 TC≥25%, n (%)
    EGFR mutation-negative (n=65)
    Screened population (n=65)	44 (68)	23 (35)
    EGFR mutation-positive (n=128)
    Screened population (n=128)	65 (51)	10 (8)
    Randomized to treatment (n=106)	52 (49)	8 (8)
    Randomized to osimertinib (n=54)	28 (52)	3 (6)
    Randomized to SoC EGFR-TKI (n=52)	24 (46)	5 (10)

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    There was PFS benefit with osimertinib versus SoC regardless of whether tumors were PD-L1-expressers (TC≥1%) or -negatives (TC<1%). Using the TC≥25% threshold, PD-L1 prevalence was lower in EGFR mutation-positive than mutation-negative samples; there were insufficient patients with TC≥25% tumors for PFS assessment.

    These results support the efficacy of EGFR-TKIs, including osimertinib, as first-line treatment of EGFRm advanced NSCLC, irrespective of PD-L1 expression.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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