Abstract 1963P
Background
Chordoma is a rare type of bone cancer with limited treatment options. Encouraging results showing the efficacy of pembrolizumab, a PD1 checkpoint inhibitor, in chordomas have recently been reported. Here, we performed comprehensive molecular testing to dissect the immune profile of these tumors and elucidate mechanisms of therapy response in chordomas.
Methods
Whole exome sequencing (WES) and whole transcriptome analysis was performed on samples from 14 patients (n = 6 samples from skull base, n = 8 samples from spine) with chordoma. Retrospective analysis of BostonGene’s Tumor Portrait® test results identified genomic and transcriptomic alterations of chordomas and classified tumor microenvironment (TME) subtypes according to methods from Bagaev, et al., 2021.
Results
The median age of patients was 54.5 years (range: 26-76 years). The histologic subtypes were conventional (n = 13) and dedifferentiated (n = 1). The median number of prior therapies was 1 (range: 0-3). Transcriptomic-based TME classification revealed 93% (n = 13) of patients had an immune-enriched (IE) TME subtype characterized by high levels of B cells and CD4+ T cells and low levels of tumor-associated macrophages. Only one patient had a fibrotic TME characterized by minimal immune infiltration and a high prevalence of stromal elements. High CD274 (PD-L1) expression was observed in 57% of samples. EGFR expression was high in all samples. In three cases, a 22q deletion was identified. Other clinically actionable events included SMARCB1 loss (n = 3), TP53 alteration (n = 2), BRCA1 loss (n = 1), a combination of PTEN, NF2, and TRAF2 loss (n = 1), and CDKN2A/B loss (n = 1). All samples were microsatellite stable and had low tumor mutational burden (range: 0.31-1.32 mut/Mb). From this cohort, 50% of patients were matched with at least one clinical trial based on their molecular profiles.
Conclusions
The prevalence of IE TME subtypes in chordomas supports the previously reported response to immune checkpoint inhibitors in chordomas. Together, these findings indicate next-generation sequencing could be a useful tool for informing treatment selection in advanced chordomas.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
BostonGene, Corp.
Funding
BostonGene, Corp.
Disclosure
M. Voropaeva, I. Zhuk, A. Aukhadieva, K. Zirov, A. Makarova, L. Bednyagin: Financial Interests, Personal, Full or part-time Employment: BostonGene, Corp. A. Bagaev: Financial Interests, Personal, Full or part-time Employment: BostonGene, Corp.; Financial Interests, Personal, Stocks/Shares: BostonGene, Corp.
Resources from the same session
1840P - RNASEH2B loss and PARP inhibition (parpi) in metastatic castration resistant prostate cancer (mCRPC)
Presenter: Juliet Carmichael
Session: Poster session 15
1841TiP - Darolutamide plus androgen-deprivation therapy (ADT) in patients with high-risk biochemical recurrence (BCR) of prostate cancer: A phase III, randomized, double-blind, placebo-controlled study (ARASTEP)
Presenter: Alicia Morgans
Session: Poster session 15
1842TiP - Phase II randomized trial of two dose levels of vobramitamab duocarmazine in participants with metastatic castration resistant prostate cancer (mCRPC; TAMARACK)
Presenter: Johann de Bono
Session: Poster session 15
1922P - Immunosarc II master trial: phase II of sunitinib and nivolumab in vascular sarcomas cohort - A GEIS, ISG and UCL study
Presenter: Nadia Hindi Muñiz
Session: Poster session 15
1923P - Combined analysis of phase III ANNOUNCE study and phase II study exploring olaratumab in advanced soft tissue sarcoma
Presenter: Yoichi Naito
Session: Poster session 15
1924P - Targeting microenvironment and cellular immunity in sarcomas with trabectedin combined with metronomic cyclophosphamide: The TARMIC study
Presenter: Cheng-Ming Sun
Session: Poster session 15
1925P - Results of SOC-2082 phase II study using metronomic gemcitabine, doxorubicin, and docetaxel plus nivolumab as second/third-line therapy for advanced leiomyosarcoma
Presenter: Neal Chawla
Session: Poster session 15
1926P - Trabectedin plus radiotherapy on symptomatic advanced sarcoma patients: Results from the SYNERGIAS study - A Spanish group for research in sarcoma (GEIS) phase II study
Presenter: Javier Martin-Broto
Session: Poster session 15
1927P - Epithelioid hemangio-endothelioma (EHE) in NETSARC: The nationwide series of 267 patients over 12 years
Presenter: Axel Le Cesne
Session: Poster session 15
1928P - Differential presentation and outcome of sclerosing epithelioid fibrosarcoma (SEF) vs low grade fibromyxoid sarcoma (LGFMS): The nationwide series of 330 patients in NETSARC since 2010
Presenter: Jean-Yves Blay
Session: Poster session 15