Author of

• 20167

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  P2.03 - Chemotherapy/Targeted Therapy (ID 704)

  • Event: WCLC 2017
  • Type: Poster Session with Presenters Present
  • Track: Chemotherapy/Targeted Therapy
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)

  • 23323

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    P2.03-052 - Local Ablative Therapy for Oligoprogressive, EGFR-Mutant, Non-Small Cell Lung Cancer (NSCLC) After Treatment with Osimertinib (ID 10360)

    09:30 - 09:30  |  Author(s): D.T.W. Wong
    • Abstract

    Background:
    EGFR tyrosine kinase inhibitors (EGFR-TKIs) improve progression-free survival (PFS) in patients with EGFR-mutant NSCLC, but disease progression limits efficacy. Retrospective studies show a survival benefit to local ablative therapy (LAT) in patients with oligoprogressive disease (progression at a limited number of anatomic sites).
    
    Method:
    This is a prospective study of LAT in patients with oligoprogressive EGFR-mutant NSCLC. Patients with no prior EGFR-TKI therapy (cohort 1) or progression after 1[st]/2[nd] generation EGFR-TKIs with acquired T790M mutation (cohort 2) receive osimertinib. Upon progression, eligible patients with <= 5 progressing sites undergo LAT and resume osimertinib until disease progression. Patients previously treated with osimertinib qualifying for LAT upon disease progression are also eligible for treatment (cohort 3). Primary endpoint: evaluation of safety and efficacy of reinitiation of osimertinib after LAT (assessed by PFS2). Additional goals are assessment of mechanisms of resistance to osimertinib by multi-omics analyses of tumor, blood, and saliva.
    
    Result:
    Between 04/2016 and 06/2017, 18 patients were enrolled (cohort 1: 11, cohort 2: 4, cohort 3: 3). Median age was 57 (range 36-71). The most common adverse events (AEs) on osimertinib treatment were rash, diarrhea, thrombocytopenia, and alanine transaminase elevation with most of the AEs being grade 1 or 2. Among evaluable patients, confirmed objective response rates prior to LAT in cohorts 1 and 2 were 66.7% (6/9) and 75% (3/4), respectively, with 11.3 months median PFS (95% CI: 3.4-11.3 months) in cohort 1 and 8.9 months in cohort 2 (95% CI not defined due to the small number of patients). To date, 7 patients had progressive disease, 6 of which had oligoprogression and subsequently underwent LAT (cohort 1: 2; cohort 2: 1; cohort 3: 3). Three patients were treated with combination of surgery and radiotherapy (RT), 2 patients with surgery, and 1 patient with RT. Whole exome sequencing (WES) and RNA-seq were performed on tumor tissues obtained pre-treatment and upon progression on osimertinib. MET amplification, transformation to small cell lung cancer, and EGFR C797S mutation were identified as mechanisms of resistance to osimertinib. One patient with MET amplification was referred for a clinical trial of osimertinib and savolitinib, a MET inhibitor, upon second progression on osimertinib re-challenge, and had a response to treatment.
    
    Conclusion:
    Patients with EGFR-mutant NSCLC and oligoprogression after EGFR-TKI therapy can be safely treated with LAT. In select patients, this approach could potentially maximize duration of EGFR-TKI treatment and prevent premature switching to other systemic therapies.