Author of

• 32099

  +

  EP1.12 - Small Cell Lung Cancer/NET (ID 202)

  • Event: WCLC 2019
  • Type: E-Poster Viewing in the Exhibit Hall
  • Track: Small Cell Lung Cancer/NET
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall

  • 32139

    +

    EP1.12-37 - Higher Consistency of Mutations Between Tumor DNA and ctDNA in Small-Cell Lung Cancer Compared to Non-Small Cell Lung Cancer (ID 2060)

    08:00 - 18:00  |  Presenting Author(s): Hongxia Ma
    • Abstract

    Background
    

    Small-cell lung cancer (SCLC) is an aggressive neuroendocrine lung tumor representing 15% of lung cancers, patients with SCLC usually have a poor prognosis and limited treatment options. This is primarily due to the lack of adequate tumor tissues to assess and delaying therapy to repeat biopsies is often not possible. Circulating cell-free tumor DNA (ctDNA) based test for EGFR mutations in patients with Non-small cell lung cancer (NSCLC) has been approved by US Food and Drug Administration, however, whether it is feasible to perform genomic profiling of ctDNA from SCLC patients still have been lacking. SCLC is characterized by early hematogenous spread, we hypothesized that ctDNA sequencing in SCLC is more comprehensive as a promising biomarkers than that in NSCLC.

    Method
    

    To analyze the consistency of gene mutation sites between tumor DNA and perepheral blood ctDNA in patients with lung cancer (SCLC and advanced NSCLC), and further explore the feasibility of ctDNA as a clinical tool in SCLC. Paired tumor and blood samples were obtained from systemic treatment naïve patients with SCLC and advanced NSCLC. DNA was sequenced by target-capture deep sequencing of 808 previously annotated genes related to solid tumors.

    Result
    

    During February 2017 to April 2018, 8 SCLC and 119 advanced NSCLC patients were enrolled from 3 centers. A total of 256 somatic variations were detected in tumor DNA and ctDNA. TP53 and RB1 are the most frequently mutated genes in SCLC patients and mutations occurred most frequently in NSCLC were EGFR , TP53 , KRAS , ALK. In matched tumor DNA and ctDNA, we observed significant higher concordance of mutations in SCLC (90%) compared to NSCLC (65%). Furthermore, the variant allele frequency (VAF) of shared mutations in SCLC highly correlated to each other (r=0.68). In addition, a subset of mutations was exclusively detected in ctDNA, indicating that the genomic landscape derived from ctDNA reflects that from SCLC to a certain degree.

    Conclusion
    

    Taken together, our data showed the potential advantage of sequencing ctDNA in SCLC over than that in NSCLC to reveal the global genomic landscape. SCLC ctDNA analysis will be used as a powerful research tool that can shed light on this poorly understood disease and could also provide clinical information that benefits patients.

• 31515

  +

  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

  • 31526

    +

    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): Hongxia Ma
    • 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.