Author of

• 25921

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  P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

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

  • 26306

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    P1.01-74 - MET Exon 14-Altered Lung Cancers: Central Nervous System (CNS) Metastases and Patterns of CNS Progression on MET Inhibition. (ID 14263)

    16:45 - 18:00  |  Author(s): Ai Ni
    • Abstract
    • Slides

    Background
    

    MET exon 14 (METex14) alterations are targetable drivers found in 3-4% of lung cancers. The frequency of intracranial disease and patterns of central nervous system (CNS) progression on MET tyrosine kinase inhibitors (TKI) are not well characterized.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Patients with advanced METex14-altered lung cancers identified by next-generation sequencing (MSK-IMPACT) between January 2014 and March 2018 were eligible for analysis. A retrospective review of clinical features, patterns of metastases, and CNS progression on MET-TKI was performed. The frequency of intracranial disease was compared to cohorts single-center of EGFR-mutant (n=200), ERBB2-mutant (n=98) and KRAS-mutant (n=200) lung cancers.

    4c3880bb027f159e801041b1021e88e8 Result
    

    82 patients with metastatic METex14-altered lung cancers were identified. The median age was 73; 56% (n=46) were female and 54% (n=44) were former smokers. The frequency of brain metastases at baseline was 11% (n=9/82). The lifetime frequency of intracranial metastases from diagnosis of metastatic disease was 34% (n=28/82). By comparison, the frequency of brain metastases was 47% (94/200, p=0.05) with EGFR-, 47% (46/98), p=0.09) with ERBB2-, and 32% (64/200, p=0.78) with KRAS-driven tumors. 6% (n=5/82) of patients developed leptomeningeal disease. The overall survival (OS) of patients who developed intracranial disease on therapy compared to those who did not develop intracranial disease was not significantly different (HR 0.66, 95% CI 0.30-1.43, p=0.29). 51 patients received crizotinib, 26 of whom developed progressive disease. The frequency of intracranial (alone), intracranial and extracranial, and extracranial (alone) progression was 8% (2/26), 19% (5/26), and 73% (19/26), respectively.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    A third of patients with METex14-altered lung cancers develop intracranial disease. This proportion is lower than that seen in EGFR- and ERBB2-mutant lung cancers and comparable to KRAS-mutant lung cancers. The frequency of CNS failure on crizotinib was lower than expected compared to historical rates in ALK-rearranged lung cancers.

    6f8b794f3246b0c1e1780bb4d4d5dc53

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• 25943

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  P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 27050

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    P2.06-40 - VISTA is Highly Expressed in Malignant Pleural Mesothelioma (MPM) and Independent of PD-L1 Expression (ID 13232)

    16:45 - 18:00  |  Author(s): Ai Ni
    • Abstract

    Background
    

    PD-1 blockade is effective in only a minority of MPM patients and predictors of response in MPM are unclear. Recent TCGA analysis of MPM revealed VISTA (V-domain Ig-containing suppressor of T cell activation), another inhibitory T cell checkpoint protein, to be frequently expressed in MPMs. In search of other immunotherapeutic targets in MPM, we evaluated the expression of VISTA, its relationship with expression of PD-L1, and the association with response to PD-1 blockade in MPM.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    We retrospectively interrogated the MPM database at Memorial Sloan Kettering to identify patients who received immune checkpoint inhibitors (ICIs). Archival tissue, where available, was obtained and we performed immunohistochemistry (IHC) using antibodies to PD-L1 (clone E1L3N) and VISTA (clone D1L2G), both from Cell Signaling Technology. Imaging studies were reviewed with a thoracic radiologist according to the modified RECIST criteria.

    4c3880bb027f159e801041b1021e88e8 Result
    

    37 patients were identified as having received at least one dose of ICI, of whom 26 patients had tissue for VISTA/PD-L1 testing. VISTA was positive (>1%) in 25 (96%) and >50% in 22 (84%). PD-L1 was positive in 11 (42%) and >50% in two (8%). No evident correlation between VISTA and PD-L1 expression was seen. Correlation with response will be reported.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    In contrast to PD-L1, VISTA is highly expressed in most patients with MPM. Its expression appears independent of PD-L1 expression. Molecules targeting VISTA and its ligand should be prioritized for clinical development in MPM.

    6f8b794f3246b0c1e1780bb4d4d5dc53