Abstract 5449
Background
Limited data are available on effectiveness and safety of systemic therapies for treatment of advanced (unresectable and/or metastatic) epithelioid sarcoma (ES). This natural history study collected real-world (rw) data on outcomes of ES patients (pts) receiving at least first-line (1L) or 2 or more lines (2L+) of systemic therapies.
Methods
Retrospective chart review was conducted in pts with advanced ES who initiated systemic therapy between 2000-2017 at 5 US cancer centers. Due to unavailability of RECIST assessment, rw overall response rate (rwORR) was assessed by review of radiology reports. rw disease control rate (rwDCR) was defined as percent of pts with response of any duration or stable disease ≥32 wks. Median rw duration of response (rwDOR), rw progression-free survival (rwPFS) and overall survival (OS) were estimated from start of therapy by Kaplan-Meier method. The index date for time-to-event endpoints was the start of first-line treatment. Adverse events (AEs) resulting in treatment modification, discontinuation, hospitalization, permanent sequelae or death, were abstracted.
Results
Of 74 eligible pts, 53 (71.6%) were male, and 63 (85.1%) had metastatic ES. INI1/BAF47 was not expressed in 90.2% of 41 tumors tested. Mean age at advanced ES diagnosis was 36.4 years. Anthracycline-based (54.1%) and gemcitabine-based (24.3%) regimens were most common in 1L. Median (range) number of lines of therapy received was 2 (1-7). 1L rwORR was 14.9%, rwDCR was 20.3%, rwDOR was 14.5 wks, and median OS was 66.3 wks. The table shows 1L and 2L+ results. Over 50% of pts had an AE; most frequently febrile neutropenia (13.5%), pain (9.5%), anemia, dyspnea, fever, thrombocytopenia and transaminitis (5.4% each).Table:
1687P Real-world outcomes by line of therapy
1L N = 74 | 2L+ N = 46 | |
---|---|---|
rwORR (95% CI), % | 14.9 (7.7-25.0) | 9.4 (4.4-17.1) |
Median rwDOR (95% CI), wks | 14.5 (9.1-22.6) | 19.6 (3.1-24.3) |
rwDCR (95% CI), % | 20.3 (11.8-31.2) | 19.8 (12.4-29.2) |
Median rwPFS (95% CI), wks | 11.0 (7.3-29.9) | 26.0 (13.9-32.0) |
Median OS (95% CI), wks | 66.3 (49.6-94.1) | 43.3 (33.6-78.3) |
Conclusions
Currently available systemic therapies are not specific for advanced ES, have a limited response durability and low tolerability. This is the largest US-based rw study that provides benchmarking treatment efficacy and safety data for development of standard of care therapies for ES.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Epizyme, Inc.
Funding
Epizyme, Inc.
Disclosure
M.M. Gounder: Advisory / Consultancy, Travel / Accommodation / Expenses: Epizyme; Honoraria (self), Advisory / Consultancy: Karyopharm; Honoraria (self), Advisory / Consultancy: Daiichi; Honoraria (self): TRACON; Honoraria (self): Amgen. P. Merriam: Advisory / Consultancy: Lilly. S.R. Patel: Advisory / Consultancy, Research grant / Funding (self): Janssen; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: MJ Hennessey/Onc Live; Advisory / Consultancy: Novartis; Advisory / Consultancy: Immune D; Research grant / Funding (self): Eisai; Research grant / Funding (self): Blueprint Medicines; Research grant / Funding (self): Bavarian Nordic. R. Chugh: Advisory / Consultancy: Epizyme, Janssen ,EMD Serono; Research grant / Funding (institution): AADi (Institution), Novartis (Institution), Lilly (Institution), Medivation (Institution), Advenchen (Institution), Epizyme (Institution), Plexiconn (Institution), Pfizer (Institution); Research grant / Funding (self): Portoia Pharmaceuticals. M. Thorton: Research grant / Funding (self): Epizyme; Advisory / Consultancy: Biologics Consulting Group; Shareholder / Stockholder / Stock options: Ziopharm, Novavax, Zogenix. B.A. Van Tine: Advisory / Consultancy, Research grant / Funding (institution): Epizyme. A.H. Abdelhamid: Research grant / Funding (institution): Dubai Harvard Foundation. P. Joshi: Full / Part-time employment: Epizyme. J. Whalen: Full / Part-time employment: Epizyme. J. Yang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Epizyme. A. Rajarethinam: Shareholder / Stockholder / Stock options, Full / Part-time employment: Epizyme. M.S. Duh: Research grant / Funding (self): Epizyme, Novartis, GlaxoSmithKline, Janssen, Pfizer, Bayer, Taiho Pharmaceutical; Speaker Bureau / Expert testimony: AbbVie. P.J. Bobbili: Research grant / Funding (self): Epizyme, Novartis, AstraZeneca, GlaxoSmithKline. C.L. Cavanaugh: Research grant / Funding (institution): Epizyme, GlaxoSmithKline, NovoNordisk, Merck, Eisai, AstraZeneca. L. Huynh: Research grant / Funding (institution): Epizyme, Novartis, Pfizer, Taiho Pharmaceutical; Travel / Accommodation / Expenses: Novartis. T. Totev: Research grant / Funding (institution): Epizyme, Novartis, Takeda (formerly Shire). G. Demetri: Shareholder / Stockholder / Stock options: Blueprint Medicines, Merrimack G1 Therapeutics; Caris Life Sciences; Chapions Oncology; Besson Phramceuticals; Advisory / Consultancy: Novartis, Pfizer, EMD Serono, Jannsen, Ignyta, Loxo, Mirati Therapeutics, Epizyme, PharmaMar, Daiichi Sankyo, WIRB-copernicus group, Ziopharm Oncology, Polaris, Bluprint Medicines, Merrimack, G1 Therapeutics, Caris Life Sciences, Champions Oncology, Besso; Research grant / Funding (institution): Bayer, Novartis, Pfizer, Jannsen, Ignyta, Loxo, AbbVie, Epizyme, AdaptImmune.; Licensing / Royalties: Novartis. All other authors have declared no conflicts of interest.
Resources from the same session
4615 - Proteomic Profiling Identifies Molecular Basis of Adverse Event to BPM31510 Exposure: Rationale for Comprehensive Molecular Pharmacodynamics (PD) in Phase 1 Clinical Trial Design
Presenter: Vivek Subbiah
Session: Poster Display session 1
Resources:
Abstract
5052 - Identification of first-in-class, naturally occurring LAG3 checkpoint inhibitor
Presenter: Gennady Bratslavsky
Session: Poster Display session 1
Resources:
Abstract
5336 - Are Epigenetic therapies modifying sensitivity to conventional chemotherapy?
Presenter: Alexandra Bizot
Session: Poster Display session 1
Resources:
Abstract
5739 - Oncogenic mutations at the dimer interface of EGFR lead to formation of covalent homo-dimers and allosteric activation of the kinase domain: A mechanism which alters the selectivity profile of oncogenic EGFR.
Presenter: Elizabeth Buck
Session: Poster Display session 1
Resources:
Abstract
5492 - Basic selective estrogen receptor degraders (B-SERDs) in combination with novel BET inhibitors in ER+ breast cancer
Presenter: Rui Xiong
Session: Poster Display session 1
Resources:
Abstract
5965 - EPI-7386 is a novel N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer
Presenter: Ronan Le Moigne
Session: Poster Display session 1
Resources:
Abstract
3582 - AVID200 neutralizes TGF-beta1 and -beta3, the principal immunosuppressive TGF-beta isoforms overexpressed by tumors, and sensitizes tumors to immune checkpoint inhibitors.
Presenter: Tina Gruosso
Session: Poster Display session 1
Resources:
Abstract
1996 - High NAMPT expression and anti-tumor activity of NAMPT inhibitor in adult T-cell leukemia/lymphoma
Presenter: Tomohiro Kozako
Session: Poster Display session 1
Resources:
Abstract
4307 - TPX-0046 is a novel and potent RET/SRC inhibitor for RET-driven cancers
Presenter: Alexander Drilon
Session: Poster Display session 1
Resources:
Abstract
4869 - In Vivo Evaluation of Cisplatin-loaded PEG-PCL Block Copolymeric Nanoparticles for Anticancer Drug Delivery
Presenter: Yingtzu Yen
Session: Poster Display session 1
Resources:
Abstract