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Lingjun Zhu



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    P1.14 - Targeted Therapy (ID 182)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.14-38 - Identification of FGFR1-3 Fusions in Lung Cancers Using Comprehensive Next-Generation Sequencing (Now Available) (ID 2071)

      09:45 - 18:00  |  Author(s): Lingjun Zhu

      • Abstract
      • Slides

      Background

      Fusions have been described in the fibroblast growth factor receptors (FGFR) 1-3 genes with multiple partners in a variety of tumors. Here we focused on the prevalence of FGFR fusions in lung cancers for whom might benefit from FGFR inhibitors in clinical development.

      Method

      We reviewed FGFR alterations in 10833 lung cancer patients (pts) who underwent genetic testing at our institute from 2016 to 2019. Mutation profiles were analyzed using hybridization capture based next-generation sequencing (NGS), which covers all exons of FGFR1-3 and specific intron regions containing the break points of fusions. All patients were also analyzed for mutations in EGFR, KRAS, HER2, BRAF, ALK, RET, MET, ROS1, as well as other oncogenes.

      Result

      FGFR fusions were identified in 25 lung cancer pts, including 9 adenocarcinoma pts, 4 squamous-cell carcinoma pts, 1 patient with large cell neuroendocrine carcinoma and 11 pts with non-specific pathology. FGFR3-TACC3 fusion was detected in 72% (18/25) of pts and the remaining were previously unreported fusions (table). Concurrent EGFR mutations were identified in 44% (11/25) of pts with FGFR fusions (32%, treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs); 12%, not treated with EGFR-TKIs). PI3K-AKT-MTOR signaling pathway was also activated in 28% (7/25) of pts, and cell-cycle gene alterations were also detected in 16% (4/25) of pts.

      Table. Frequency of FGFR fusions

      Fusions

      Fusion region

      N (%)

      FGFR3-TACC3

      EX17:EX11

      6 (24%)

      EX18E:EX11

      4 (16%)

      EX18E:EX13

      2 (8%)

      EX17:EX10

      2 (8%)

      others

      4 (16%)

      FGFR1-chr8:21672159

      EX1:chr8:21672159

      1 (4%)

      FGFR1-MTUS1

      EX19E:EX8

      1 (4%)

      EFHA2-FGFR1

      EX2:EX3

      1 (4%)

      TNRC18-FGFR1

      PMT:EX10

      1 (4%)

      ZMAT4-FGFR1

      EX2:EX2

      1 (4%)

      ZNF696-FGFR1

      EX2:EX18E

      1 (4%)

      OPALIN-FGFR2

      EX6E:EX2

      1 (4%)

      Total

      25 (100%)

      Conclusion

      FGFR1-3 fusions define a unique molecular subtype of lung cancer. Depending on the concurrent genetic alterations, combined targeted therapy might be an optimal strategy to control tumor growth for these pts.

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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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      P2.14-09 - Concurrent TP53 Mutation Adversely Impact the Efficacy of Crizotinib in ROS1-Rearranged Lung Cancer Patients (ID 2158)

      10:15 - 18:15  |  Author(s): Lingjun Zhu

      • Abstract

      Background

      ROS1 tyrosine kinase inhibitors (TKIs) are now standard of care for patients with advanced ROS1-rearranged NSCLC. But factors that may affect the efficacy of ROS1 TKIs remain to be explored.

      Method

      We conducted a retrospective multicenter study of lung cancer patients with ROS1 rearrangements. Treatment and survival follow-up was done and clinical records were reviewed. PFS distribution was analyzed by Kaplan-Meier method with log-rank test.

      Result

      In total, we included 94 lung cancer patients with ROS1 fusion genes profiled by next-generation sequencing from May 2016 to September 2018. Fifty of them were female. The median diagnosis age was 54 (25-83). The most common histologic type was adenocarcinoma, which was confirmed in 75 of 78 patients with available pathological results. The most common fusion partners were CD74, EZR, SDC4 and SLC34A2 identified in 42, 19, 12 and 8 patients respectively. Concurrent actionable mutations were uncommon for ROS1 fusion-positive patients. The most frequent concomitant mutated gene was TP53, which was detected in 33% of all the patients. After excluding 29 patients who were lost to follow-up at the very start, the median follow-up time was 8.5 (0-28) months from the moment when mutation profiling was performed. Thirty-nine patients received treatment with crizotinib, among whom 27 were treatment-naïve patients. The median PFS of the 39 patients with crizotinib was not reached yet. Patients with baseline CNS metastasis tend to have shorter PFS compared to patients without (median, 12 vs NR, p = 0.0073). Besides, concurrent TP53 mutations were correlated with worse PFS (median, both NR, p = 0.0417). Mutation profiles of 10 patients were derived from ctDNA testing. No difference was found in PFS between these 10 patients with others whose genomic profiles were based on fresh tissue or FFPE specimens, suggesting that plasma ctDNA serves as good specimen source for mutation profiling to monitor clinical treatment.

      Conclusion

      Concurrent TP53 mutation and presence of CNS metastasis are associated with decreased PFS of ROS1-positive patients treated with crizotinib.