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L. Mezquita

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    Immunotherapy and next-generation TKIs: From second to frontline treatment (ID 55)

    • Event: ELCC 2018
    • Type: Poster Discussion session
    • Track:
    • Presentations: 1
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      144PD - Leptomeningeal metastases in EGFR-mutated non-small cell lung carcinoma: Management after tyrosine kinase inhibitors (ID 611)

      07:45 - 09:00  |  Author(s): L. Mezquita

      • Abstract
      • Slides

      Leptomeningeal metastases (LM) in non-small-cell lung carcinoma (NSCLC) are associated with poor outcome. Tyrosine kinase inhibitors (TKIs) are active in LM+ EGFR mutated (EGFRm) patients (pts), but optimal patient's management after failure of TKIs is unknown.

      We included consecutive pts with EGFRm NSCLC who had LM progression during first-line EGFR TKI, defined as diagnosis of LM during TKI treatment or progression of known LM after first-line TKI, treated in our institution. Clinical and pathological data were retrospectively collected. We evaluated overall survival (OS), progression-free survival (PFS), clinical response rate (CRR), and disease control rate (DCR) defined as clinical response or stable disease >2 months.

      We included 66 pts treated between Apr. 2003 and Sept. 2016, with a median age of 54 years [26–79]; 51 (77%) were females; 56 (85%) non-smokers. Twenty-three tumors (35%) had exon 19 deletion, 23 (35%) L858R exon 21 mutation, 10 (15%) T790M mutation. Median number of previous lines was 2 [1–7], and 19 pts (29%) had additional intrathecal treatment. 2[nd] line TKI was given to 36 pts (55%): 19 (53%) received erlotinib, 10 (28%) high dose (HD) erlotinib (300 mg daily), 3 osimertinib, 4 other 1[st]/2[nd] generation TKI (3 gefitinib, 1 afatinib). Median PFS and OS from LM progression were 3 months (m) [CI95% 2–3] and 7 m [CI95% 3–16], respectively. CRR and DCR for 2nd-line TKI were 43% and 77%. Nine pts (25%) were alive at 10 m (6 erlotinib, 1 HD erlotinib, 2 osimertinib). Median OS for erlotinib, HD erlotinib, osimertinib and other 1[st]/2[nd] generation TKI were 8 m (CI 95% 7–16), 3 m (CI 95% 2-not reached (NR)), NR (CI 95% NR-NR), and 2.5 m (CI 95% 0-NR), respectively. Patients treated with erlotinib, of whom 79% received prior afatinib or gefitinib, had better OS compared to patients treated with other 1[st]/2[nd] generation TKI (8 m vs. 2.5 m, P = 0.04). CRR and DCR in patients with HD erlotinib were 40% and 60%, respectively, of whom 80% received prior erlotinib.

      2[nd]-line TKI can increase survival in LM+ EGFRm NSCLC previously treated with TKI. Sequential erlotinib after prior gefitinib or afatinib seems to be a suitable strategy. Increasing erlotinib dose has demonstrated clinical benefit.

      Clinical trial identification:

      Legal entity responsible for the study:
      Gustave Roussy

      Has not received any funding

      All authors have declared no conflicts of interest.

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