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Joon Ho Shim



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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-54 - High Incidence of CNS Metastases in Advanced or Recurrent Non-Small Cell Lung Cancer Patients with RET Fusion (ID 1758)

      10:15 - 18:15  |  Author(s): Joon Ho Shim

      • Abstract

      Background

      Chromosomal rearrangements involving RET, with incidence of 1-2% in non-small-cell lung cancer, define a distinctive molecular subset. Here, we aim to determine the clinicopathological characteristics of patients with advanced NSCLC harboring the RET fusion gene.

      Method

      We identified 59 consecutive cases with RET rearrangements by using break-apart fluorescence in situ hybridization (n=14), next-generation sequencing (n=37), or both (n=8). Clinical data, including baseline characteristics, initial presentation, responses to chemotherapy and/or immunotherapy were retrospectively analyzed.

      Result

      The median age was 56 years, and 53% of patients were male. Approximately half of the patients (51%) were never-smokers. Adenocarcinoma was the predominant histologic subtype (90%), followed by pleomorphic (3%), neuroendocrine (3%), squamous cell (2%), and small cell carcinoma (2%). For the 19 patients with small primary lesions (<3cm), 32% (6/19) had N2 and 37% (7/19) had N3 disease. 17 patients (29%) had an intracranial lesion at the initial presentation or at the time of recurrence, and additional 11 patients (19%) developed brain metastasis during follow-up. Cerebrospinal fluid cytology exam confirmed leptomeningeal seeding in four patients (7%) with concomitant parenchymal metastasis. The median time to development of brain metastases was 19.0 months (range 3.8-51.8).

      Of 30 patients whose fusion partners were identified, kinesin family member 5B (KIF5B) was the most common, followed by coiled-coil domain containing 6 gene (CCDC6), nuclear receptor coactivator 4 (NCOA4), and myosin 5C (MYO5C) and lisH domain and HEAT repeat-containing protein KIAA1468 homolog (KIAA1468). Additionally, a novel fusion partner, phytanoyl-CoA 2-hydroxylase interacting protein like (PHYHIPL), was reported in one patient. Only two patients harbored concomitant EGFR mutation, and no ALK alterations were reported.

      The median overall survival was 35.3 months (95% confidence interval [CI]: 21.7-48.9). In 46 patients who were treated with pemetrexed-based chemotherapy, the overall response rate (ORR) and progression-free survival (PFS) time were 53.0% and 8.5 months (95% CI: 6.3-10.7), respectively. In 13 patients who were treated with immunotherapy, the ORR and PFS were 7.7% and 1.5 months (95% CI: 1.3-1.7), respectively, with no significant difference according to the level of PD-L1 expression.

      Conclusion

      Our study revealed the unique clinical characteristics and outcomes of advanced NSCLC patients harboring RET fusion gene. Considering the high incidence of CNS metastases, relatively poor response to immunotherapy, and a recent development of RET kinase inhibitors (such as cabozantinib and vandetanib), more efforts are warranted for identification of patients with RET fusion as a candidate for targeted therapies.