In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e14555-e14555
Abstract:
e14555 Background: The optimal systemic treatment for pulmonary large-cell neuroendocrine carcinoma (LCNEC) is still under debate. Previous studies showed that LCNEC with different genomic characteristics might respond differently to different chemotherapy regimens suggesting the potential role of genomic profiling in therapeutic decision-making. Tumor biopsies are often inadequate for genomic profiling, while cell-free DNA (cfDNA) analysis has demonstrated great potential in genomic profiling. Methods: A total of 63 patients with LCNEC treated with different chemotherapy regimens (etoposide-platinum doublets, pemetrexed with platinum and gemcitabine, docetaxel, or paclitaxel with platinum, hereafter referred to as SCLC-PE, NSCLC-PEM and NSCLC-GEM/TAX) were enrolled in this study. Samples were collected and included tumor DNA only from 22 patients, cfDNA only from 18 patients and paired tumor DNA and plasma cfDNA from 23 patients. Tumor DNA and cfDNA were sequenced by target-captured 179 genes from Geneplus-Beijing or Oncomine Cancer Panel v3 or 70 genes panel from Guardant 360. Survival and response analyses were only applied to 54 patients who received first line chemotherapy. Results: The mutation landscape of frequently mutated cancer genes in LCNEC from cfDNA closely resembled that from tumor DNA, which led to a 90% concordance in genomic subtyping. We classified LCNEC harboring any of these alterations: RB1 mutation/loss, PTEN mutation/loss, FGFR1/FGFR4 mutation/amplification, TP53 loss, as “SCLC-like” tumors, otherwise as NSCLC-like. Overall, patients with SCLC-like LCNEC had a shorter overall survival (OS) than those with NSCLC-like LCNEC (10.3 vs 14.4 months, p = 0.32) despite higher response rate (RR) (41% vs 22%) to chemotherapy. Furthermore, treatment with SCLC-PE was associated with longer PFS in SCLC-like LCNEC compared to NSCLC-PEM and NSCLC-GEM/TAX (median 8.3 vs 2.3 months, p = 0.0002; median 8.3 vs 5.9 months, p = 0.05), while treatment with NSCLC-GEM/TAX led to a shorter survival compared to SCLC-PE (median 1.9 vs 4.1 months, p = 0.03) or NSCLC-PEM in NSCLC-like LCNEC patients (median 1.9 vs 4 months, p = 0.07). Conclusions: Genomic subtyping has potentials in prognostication and therapeutic decision-making for patients with LCNEC and cfDNA analysis is a reliable alternative for genomic profiling of LCNEC.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.15_suppl.e14555
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2019
detail.hit.zdb_id:
2005181-5
