The American Society of Clinical Oncology (ASCO) annual meeting took place this year in Chicago between June 1-5, 2018

Here are eight Alveolar Soft Part Sarcoma (ASPS) related abstracts from the meeting. Of these, seven describing results of clinical trials with the following treatments:

1. Phase III of Anlotinib
2. Phase II trial of Axitinib plus pembrolizumab
3. Phase II trial of Cediranib
4. Phase II trial of Apatinib
5. Phase II trial of Crizotinib
6. Phase I/II of Sunitinib plus nivolumab
7. Phase I trial of JS001 anti PD-1 inhibitor

1. Anlotinib for metastasis soft tissue sarcoma: A randomized, double-blind, placebo-controlled and multi-centered clinical trial.

Author(s): Yihebali Chi, Yang Yao, Shusen Wang, Gang Huang, Qiqing Cai, Guanning Shang, Guowen Wang, Guofan Qu, Qiong Wu, Yu Jiang, Jianmin Song, Jing Chen, Xia Zhu, Zhengdong Cai, Chunmei Bai, Yongkui Lu, Zhihua Yu, Jingnan Shen, Jianqiang Cai; National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Affiliated Sixth People’s Hospital, Shanghai Jiaotong University, Shanghai, China; Sun Yat-sen University Cancer Center, Guangzhou, China; Hunan Cancer Hospital, Changsha, China; Henan Cancer Hospital, Zhengzhou, China; Liaoning Cancer Hospital and Institute, Shenyang, China; Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; Harbin Medical University Cancer Hospital, Harbin, China; The First Affiliated Hospital of Bengbu Medical College, Bengbu, China; Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China; Gansu Provincial Cancer Hospital, Lanzhou, China; Wuhan Union Hospital, Wuhan, China; The First Affiliated Hospital of Fujian Medical University, Fuzhou, China; The First People’s Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China; Peking Union Medical College Hospital/ Chinese Academy of Medical Sciences, Beijing, China; Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; Jiangxi Cancer Hospital, Nanchang, China; Department of Musculoskeletal Oncology, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

Background: No standard therapy is available in China for soft tissue sarcoma (STS) patients progressed after first-line chemotherapy. Anlotinib has shown single-agent activity in a phase II study presented orally at 2016 ASCO. This study aimed at confirming anlotinib’s efficacy and safety in advanced STS patients after failure of standard chemotherapy.

Methods: Patients aged 18 years and older with angiogenesis inhibitor naive, histologically proven advanced STS, intolerance or failure to anthracycline-based chemotherapy, at least one measurable lesion according to RECIST 1.1, were eligible. Those patients were randomly assigned (2:1) to receive anlotinib (12 mg per day 2 weeks on and 1 week off) or placebo. The pathologic subtypes enrolled were: synovial sarcoma (SS), alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS) and others. Different pathologic subtypes were also randomly assigned (2:1) to each arm. The primary endpoint was progression-free survival (PFS). This trial was registered with ClinicalTrials.gov, number NCT02449343.

Results: 233 patients were randomly assigned to either anlotinib (n = 158) or placebo (n = 75) and included in the final analysis. The median PFS was 6.27 months (95% CI: 4.30-8.40) for anlotinib compared with 1.47 months (95% CI: 1.43-1.57) for placebo (HR=0.33, p < 0.0001); objective response rate was 10.13% versus 1.33% (p = 0.0145); disease control rate was 55.7% versus 22.67% (p < 0.0001). For SS (n = 57), the median PFS was 5.73 months versus 1.43 months (HR = 0.2, p < 0.0001). For ASPS (n = 56), the median PFS was 18.23 months versus 3 months (HR = 0.14, p < 0.0001). For LMS (n = 41), the median PFS was 5.83 months versus 1.43 months (HR = 0.19, p < 0.0001). The most common grade 3 or higher adverse events were hypertension (18.99% with anlotinib vs 0 with placebo, p = 0.00), gamma glutamyl transferase elevation (4.43% vs 1.33%, p = 0.44), triglyceride increase (4.43% vs 0, p = 0.10), low density lipoprotein elevation (3.16% vs 2.67%, p = 1.00), hyponatremia (3.16% vs 1.33%, p = 0.67) and neutrophil count reduction (3.16% vs 0, p = 0.18).

Conclusions: Anlotinib is a new treatment option for patients with advanced STS after failure of standard chemotherapy. Clinical trial information: NCT02449343

2.   A phase II trial of axitinib plus pembrolizumab for patients with advanced alveolar soft part sarcoma (ASPS) and other soft tissue sarcomas (STS).

Author(s): Breelyn A. Wilky, Matteo Maria Trucco, Despina Kolonias, Eric Wieder, Ty Subhawong, Andrew Rosenberg, Deukwoo Kwon, Wungki Park, Vaia Florou, Darcy A Kerr, Efrosyni Sfakianaki, Jaime R. Merchan, Krishna Komanduri, Jonathan C. Trent; Sylvester Comprehensive Cancer Center, Miami, FL; University of Miami, Miami, FL; University of Miami Miller School of Medicine, Miami, FL; University of Miami Sylvester Comprehensive Cancer Center, Miami, FL; University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL; Department of Pathology, University of Miami, Miller School of Medicine, Miami, FL

Background: Inhibition of programmed-death 1 (PD1) by pembrolizumab (P) produced overall response rates (ORR) of 19% in advanced STS [SARC028]. Vascular endothelial growth factor (VEGF) suppresses the immune microenvironment and may contribute to checkpoint inhibitor resistance. Axitinib (Ax) is a pan-VEGFR inhibitor that prolongs progression-free survival (PFS) in advanced STS [Axi-STS], with striking antitumor activity in combination with P in renal cell carcinoma. We report toxicity, efficacy, and correlative endpoints of combination Ax/P for patients (pts) with advanced STS.

Methods: NCT02301039 is an open-label Phase II trial of Ax/P in 30 pts with advanced or metastatic STS, requiring RECIST 1.1 progressing disease, adequate end-organ function and performance status. Pts received Ax 5 mg PO twice daily with concurrent P 200mg IV q21 days. Primary endpoint: 3-month PFS rate (PFS_3mo); secondary endpoints: toxicity, ORR and clinical benefit rate (CBR) by RECIST 1.1, and overall survival. Tumor biopsies and peripheral blood samples were obtained for correlative studies of TIL and PBMC at baseline, 3 months on treatment, and at progression.

Results: 33 pts received at least one dose of study drugs, with 30 pts evaluable for primary endpoint. Enrolled subtypes: ASPS (36%), UPS (15%), LMS (18%), other (30%). PFS_3mo was 70.3% [95% CI 50.7-83.3], with median PFS of 5.4 months [95% CI 3.02-11.6]. Best ORR was 21.9% [95% CI 5.9-33.5]. PFS_3mo in ASPS pts was 90.9% [95% CI 50.8-98.7], with best ORR of 45.5% [95% CI 18.1-75.4] and CBR of 72.7% [95% CI 39.3-92.7]. Ax/P was well-tolerated, with similar immune-related toxicity rates to prior studies. Correlative markers were analyzed by a penalized logistic regression model with bootstrapping to predict PFS_3mo. Baseline high plasma angiogenic activity, circulating neutrophil:lymphocyte ratio < 4.1, low naïve fraction CD4⁺ TIL, and low PD1⁺CD8⁺ PBMC were associated with lack of progression (AUC 0.878 [95% CI 0.743-1, p = 0.0002]).

Conclusions: Combination Ax/P is well-tolerated with promising activity in ASPS pts. Identified immune correlates associated with PFS should be validated in prospective immunotherapy trials. Clinical trial information: NCT02301039

3.   Cediranib phase II study in children with metastatic alveolar soft part sarcoma (ASPS).

Author(s): John Glod, Julia Wanda Cohen, Brigitte C. Widemann, Anne Goodwin, Joanne Derdak, Eva Dombi, Oxana Borisovna Kapustina, Seth M. Steinberg, Geraldine O’Sullivan, Shivaani Kummar, Alice P. Chen; National Cancer Institute at the National Institutes of Health, Bethesda, MD; Pediatric Oncology Branch, Clinical Center National Institutes of Health, Bethesda, MD, US; Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; National Cancer Institute, Bethesda, MD; Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD; Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick, MD; NIH/NCI, Bethesda, MD; Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD; Early Clinical Trials Development Program, DCTD, National Cancer Institute at the National Institutes of Health, Bethesda, MD

Background: ASPS, a rare, highly vascular sarcoma with a clinically indolent course, frequently presents with metastases at diagnosis. Standard sarcoma chemotherapy is ineffective. Vascular endothelial growth factor (VEGF) is a promising therapeutic target. In a phase II trial of the VEGF receptor inhibitor cediranib for adults with ASPS, the partial response (PR) rate (RECIST v1.0) was 35% (15/43;95% CI:21-51%); (Kummar S,et al. J Clin Oncol 2013; 31(18): 2296-302). We evaluated the objective-response rate [PR + complete response] of cediranib in the pediatric population (NCT00942877).

Methods: Patients (pts) ≤16 years old (yo) with metastatic, unresectable ASPS received cediranib at the pediatric maximum tolerated dose of 12 mg/m² (≅70% of the fixed adult phase II dose of 30 mg) orally daily [1 cycle (cy) = 28 days]. Response was assessed every 2 cy (RECIST v1.0). A Simon two-stage optimal design (target response rate 35%, rule out 5%, alpha = 0.1, beta = 0.1) was used. With ≥ 1 response in 6 pts, enrollment would expand to 12 pts; with responses in ≥2/12pts, cediranib would be considered active.

Results:7 pts (4 female), median age 13 yo, (range 9-15), all with pulmonary metastases, enrolled on stage 1. Best response was stable disease (SD) (median cy number = 18). 2 pts were removed from study for disease progression (cy 4 and 5), and one pt for surgical resection of primary tumor (cy 16) per pt and local oncologist choice. 5 of 7 pts had SD for ≥14 months. 4 pts with SD remain on study after 18-44+ cy. Each of these pts had 1 (n = 3) or 2 (n = 1) cediranib dose reductions for grade 2 hypertension (n = 1, cy 2), fatigue (n = 2, cy 2), and proteinuria (n = 1, cy 38), and grade 3 ALT elevation (n = 1, cy 1). No growth plate toxicity was detected on MRI.

Conclusions: Cediranib did not reach the target response rate in this small pediatric cohort; thus, no additional pts were enrolled. This is in contrast to the adult 35% PR rate. Pediatric dosing was 30% lower compared to adult dosing, which may have contributed to response differences. Prolonged SD was observed in 5 pts, but given the indolent nature of ASPS, SD cannot be clearly attributed to cediranib. Cediranib has an acceptable safety profile, with no growth plate toxicity, with several pts experiencing prolonged SD. Clinical trial information: NCT00942877

4.   Apatinib in advanced alveolar soft part sarcoma: Evidence of efficacy and safety

Author(s): Li Min, Yong Zhou, Fan Tang, Yi Luo, Wenli Zhang, Rui Shi, Hong Duan, Chongqi Tu; Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, China

Background: Alveolar soft part sarcoma (ASPS) is a rare soft tissue sarcoma with high metastatic potential and poor prognosis, and it mainly affects young patients. As ASPS is resistance to chemotherapy, antiangiogenic agent sunitinib is the only therapeutic option recommended by NCCN Guidelines Version 2017. Previous studies have suggested that apatinib, an oral VEGFR-2 inhibitor, is safe and effective in some sarcomas. The aim of this study was to evaluate the efficacy and safety of apatinib for advanced ASPS.

Methods: This retrospective series analyzed 6 advanced ASPS patients who received apatinib from 2015 to 2017 at West China Hospital, Sichuan University. Among the 6 patients, there were 1 patient with unresectable local tumor and 5 patients with multiple unresectable lung metastases. Apatinib 500mg was administered once daily. Five of the 6 patients had no previous exposure to other antiangiogenic agents. Tumor responses were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Toxicities were also evaluated according to the National Cancer Institute Common Toxicity Criteria version 4.0 (CTC4.0).

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Conclusions: Apatinib showed promising antitumor activity in patients with ASPS with tolerated adverse effects, when treated as first-line or second line treatment.

5.   Activity and safety of crizotinib in patients with advanced, metastatic alveolar soft part sarcoma (ASPS) with rearrangement of TFE3:European Organization for Research and Treatment of Cancer (EORTC) phase 2 trial 90101 CREATE.

Author(s): Patrick Schoffski, Agnieszka Wozniak, Bernd Kasper, Steinar Aamdal, Michael Gordon Leahy, Piotr Rutkowski, Sebastian Bauer, Hans Gelderblom, Antoine Italiano, Lars H Lindner, Ivo M. Hennig, Sandra J. Strauss, Branko Zakotnik, Alan Anthoney, Birgit Geoerger, Jean-Yves Blay, Peter Reichardt, Winette TA van der Graaf, Sandrine Marreaud, Silvia Stacchiotti; Department of General Medical Oncology Leuven Cancer Institute, University Hospitals Leuven, KU Leuven, Leuven, Belgium; Leuven Cancer Institute, KU Leuven, Leuven, Belgium; University of Heidelberg, Mannheim University Medical Center, ITM – Interdisciplinary Tumor Center Mannheim, Sarcoma Unit, Mannheim, Germany; The Norwegian Radium Hospital, Oslo, Norway; Christie Hosp NHS Trust, Manchester, United Kingdom; Maria Sklodowska-Curie Institute – Oncology Center, Warsaw, Poland; West German Cancer Center, University Hospital Essen, Essen, Germany; Leiden University Medical Center, Leiden, Netherlands; Institut Bergonié, Bordeaux, France; University Hospital Munich-Grosshadern, Ludwig Maximilian University, Munich, Germany; Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom; University College Hospital, London, United Kingdom; Institute of Oncology Ljubljana, Ljubljana, Slovenia; Leeds Cancer Research UK Clinical Centre, Leeds, United Kingdom; Gustave Roussy, Villejuif, France; Centre Léon Bérard, Lyon, France; HELIOS Klinikum Berlin-Buch, Berlin, Germany; Radboud University Medical Center, Department of Medical Oncology, Nijmegen, Netherlands; European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium; Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Background: ASPS is an orphan disease associated with rearrangement of transcription factor E3 (TFE3), leading to abnormal MET expression. We assessed crizotinib in pts with ASPS (NCT01524926).

Methods: Eligible pts with reference pathology-confirmed ASPS received crizotinib 250 mg bid. By central FISH assessment of TFE3 rearrangement, pts were attributed to MET+ or MET– sub-cohorts. Primary endpoint was objective response rate (ORR; RECIST 1.1) according to local investigator. Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), progression-free rate (PFR), overall survival rate (OSR), overall survival (OS) and safety.

Results: Among 53 consenting pts with confirmed diagnosis of ASPS, 48 were treated and 45 were evaluable. Among 40 MET+ pts, 1 achieved a confirmed partial response (PR) lasting 215 d and 35 had stable disease (SD) (ORR: 2.5%, 95%CI: 0.6-80.6%). Further efficacy endpoints in MET+ cases were: DCR 90.0% (76.3-97.2%); 1-year PFR 37.5% (22.9-52.1%); 1-year OSR 97.4% (82.8-99.6%). Among 4 MET– pts, 1 achieved a PR lasting 801 d and 3 had SD (ORR: 25.0%, 0.6-80.6%) for a DCR of 100% (39.8-100.0%). The 1-year PFR in MET– cases was 50% (5.8-84.5%); 1-year OSR was 75% (12.8-96.1%). One pat with unknown MET status (technical failure) achieved SD but progressed after 17 cycles. Shrinkage of target lesions was seen in 17 pts, both in MET+ and – cases. The most common related AEs were nausea (34/48 [70.8%]), vomiting (22/48 [45.8%]), blurred vision (22/48 [45.8%]), diarrhea (20/48 [41.7%]) and fatigue (19/48 [39.6%]).

Conclusions: According to EORTC efficacy criteria for sarcoma, our data suggest that crizotinib has activity in TFE3 rearranged ASPS. While objective responses were infrequent, we observed tumor shrinkage in a significant proportion of pts, excellent DCR and good survival. We present very mature and reliable prospective PFS and OS estimates as reference for future research in pts with ASPS. Clinical trial information: NCT01524926

6.   IMMUNOSARC: A collaborative Spanish (GEIS) and Italian (ISG) Sarcoma Groups phase I/II trial of sunitinib plus nivolumab in selected bone and soft tissue sarcoma subtypes—Results of the phase I part.

Author(s): Javier Martin Broto, Nadia Hindi, Andres Redondo, Javier Martinez-Trufero, Silvia Stacchiotti, Emanuela Palmerini, Enrique Alava, David Silva Moura, Herminia Perez Vega, Irene Otero, Patricio Ledesma, Emanuela Marchesi, Jose A. Lopez-Martin; Virgen del Rocio University Hospital, Institute of Biomedicine Research (IBIS)/CSIC/Universidad de Sevilla, Seville, Spain; Institute of Biomedicine Research (IBIS)- Universitary Hospital Virgen del Rocio/CSIC/Universidad de Sevilla, Sevilla, Spain; Medical Oncology Department, Hospital Universitario La Paz, Madrid, Spain; Hospital Universitario Miguel Servet, Zaragoza, Spain; Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Istituto Ortopedico Rizzoli, Bologna, Italy; Hospital Virgen del Rocío-IBis, Sevilla, Spain; Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain; Hospital Universitario Virgen del Rocio, Seville, Spain; Hospital 12 de Octubre Avda de Córdoba, Madrid, Spain; Sofpromed Investigación Clínica, Palma De Mallorca, Spain; Medical Oncology Department, Hospital 12 de Octubre, Madrid, Spain

Background: Disruption of angiogenesis substantially enhances the efficacy of immune-based cancer therapies. The combination of an antiangiogenic drug (sunitinib or pazopanib) plus anti- PD1 (nivolumab) exhibited both higher activity and toxicity compared with antiangiogenic drug alone in renal cell carcinoma (RCC). We hypothesized that sunitinib (SU) and nivolumab (NI) could be synergistic in some sarcoma subtypes and the toxicity profile could be different from RCC. We present the results of phase I part of the combination of SU-NI in advanced sarcoma patients (pts).

Methods: Pretreated progressing pts, ECOG 0-1 and diagnosed with UPS, synovial sarcoma (SS), clear cell sarcoma (CCS), angiosarcoma (AS), epithelioid hemangioendothelioma (EH), solitary fibrous tumor (SFT), epithelioid sarcoma (ES), osteosarcoma (OS), Ewing sarcoma (EWS) or dedifferentiated chondrosarcoma (DCh) were eligible. SU 37.5 mg/d as induction was given for the first 14 days. The dose-finding stage (from day 15 to 45) would be completed when 10 dose limiting toxicity (DLT)-evaluated pts had been treated with DLT rate < 0.33. Two level- doses were designed: (0 initial) SU 37.5 mg/d or (-1) SU 25 mg/d along with NI 3 mg/kg/2w for both. SU-NI was maintained up to progression or intolerance.

Results: From May to October 2017, 16 pts (M/F 10/6), median age 38y (25-78) were enrolled. Diagnosis was: CSS in 4 (25%), ASPS in 3 (19%); AS, OS, SS (2 each, 12.5%); UPS, extraskeletal OS and Ch (1 each, 6%). There were three DLT in the first 6 pts at dose level 0 (G3 fatigue in 2 and G4 septic shock) and 1 DLT in the following 10 pts at level -1 (febrile neutropenia). G3/4 toxicity: fatigue 25%, thrombocytopenia 19%, mucositis 13% and neutropenia 13%. There were 6 RECIST PR (42.8%), 4 SD (2 of them 25% of shrinkage) and 4 PD in 14 evaluable pts. PR occurred in 2 CCS and in one of AS, Ch, SS, ASPS while 2 cases (ASPS and UPS) shrank 25%.

Conclusions: At the RDP2 (SU 25 mg/d and NI 3 mg/kg/2w), SU-NI is a feasible combination with manageable toxicity. SU-NI has induced objective responses in several sarcoma subtypes. The study is currently on a phase II part. Clinical trial information: NCT03277924

7.   Effect of JS001, a monoclonal antibody targeting programed death-1 (PD-1), on responses and disease control in patients with advanced or refractory alveolar soft part sarcoma: Results from a phase 1 trial.

Author(s): Sheng Yang, Jianliang Yang, Xiaohong Han, Ying Han, Shiyu Jiang, Jiarui Yao, Zhishang Zhang, Shuxiang Zhang, Peng Liu, Yan Qin, Hui Feng, Sheng Yao, Yan Sun, Yuankai Shi; Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; TopAlliance Bioscience Inc, Maryland, MD; Shanghai Junshi Bioscience Co.,LTD, Rockville, MD; Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Background: Alveolar soft part sarcoma (ASPS) is a rare and lethal malignancy mainly affecting youth, with no effective standard systemic treatment. Checkpoint inhibitors has showed efficacy in a variety of tumors, but its role in ASPS remains elusive. Here we report data of JS001, a humanized IgG4 anti-PD-1 antibody developed by Shanghai Junshi Biosciences Co., Ltd., China, in advanced or refractory alveolar ASPS from a phase 1 trial.

Methods: After a dramatic tumor shrinkage with a single injection of JS001 in a patient with ASPS, we decided to expand a cohort in this tumor. Following patients(pts) were planned to receive JS001 at 3mg/kg or 10mg/kg, repeated every 2 weeks (up to 6 doses). The diagnosis was confirmed with central histological review. PD-L1 and CD8 IHC were performed when tissue sample available.

Results: From October 2016 to June 2017, 12 pts were enrolled and all are efficacy-evaluable. One achieved CR and 2 had PR, with a response rate of 25%. Two additional pts had some degree of tumor shrinkage. Response heterogeneity was common: some lesions enlarged while others reduced in a same patient. In three pts with responses, the time to responses were 5.7, 7.7 and 23.9 weeks, respectively and the durations of response were 48.3, 31.1+ and 36.0+ weeks, respectively. Six pts remained under disease control at 6 months, and 4 at 12 months. The estimated median progression-free survival was 12.4 months. Toxicities were mostly grade 1-2. Grade 1 pneumonia and hepatitis, each in 1, were considered immune-related. No DLT or treatment-related death occurred. Tissue samples were available in 10 pts. In 4 PD-L1 positive cases, there were 2 PR, 1 SD and 1 PD; while in 2 pts with minimal CD8+ T-cell infiltration, there were 1 SD and 1 PD. In-depth biomarker analysis is in progress.

Conclusions: In this first prospective cohort of PD-1 antibody in ASPS, JS001 showed satisfactory response rate and prolonged disease control. Responses heterogeneity highlights the importance of biomarker and microenvironment study in ASPS. Our findings may prelude a new option for advanced ASPS. Clinical trial information: NCT02836834

8.   The utility of integrative genomic profiling in sarcoma diagnosis and treatment.

Author(s): Bo Zhang, Bixun Li, Zehua Wu, Fabo Qiu, Shuang Ren, Ye Qiu, Lei Mei, XiaoWei Dong, Jicheng Yao, Weifeng Wang; Peking University Third Hospital, Beijing, China; Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; The Affiliated Hospital of Qingdao University, Qingdao, China; Department of General Medicine, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China; OrigiMed, Shanghai, China

Background: Sarcomas are rare and highly heterogeneous in histological subtypes with various management protocols and prognoses. Next generation sequencing (NGS) has already been used to identify potential actionable genetic alterations and chromosomal rearrangements for diagnostic purposes in sarcomas, however it’s still challenging to select an integrative genomic profiling panel to provide valuable genetic information with reasonable medical costs in sarcoma.

Methods: FFPE tumor and matched blood samples from 82 Chinese sarcoma patients were collected for NGS-based 450 genes DNA panel assay. All classes of genomic alterations including single base substitutions, short and long insertions/deletions, copy number variations, gene rearrangements were assessed, and tumor mutational burden as well. Panel based RNAseq specially assessing gene rearrangements and expressions was performed. Results:TP53 gene mutation is the most common genomic alteration (30%) in the current Chinese sarcoma cohort including 13 cases of liposarcoma, 11 cases of osteosarcoma, 10 cases of Ewing sarcoma, 8 cases of gastrointestinal stromal tumor (GIST), 5 cases of myxoid fibrosarcoma and 14 other histologically different types. All were reviewed by two experienced pathologists. There were about 40% (33/82) of patients with at least one actionable mutations with a potential of treatment to FDA approved drugs, including PIK3CA, PTEN, KIT, MET amplifications, BRCA truncations, ROS1 and PDGFB fusions. In the 25 cases of FFPE samples underwent RNAseq, a number of gene fusions partnered with TFE3, SSX1, EWSR1, COL1A1 and FUS were detected by RNAseq, and all were validated by FISH. In addition, three out of four GIST samples underwent RNAseq showed elevated level of cKIT gene expression. A sixteen year old patient, who was diagnosed by NGS as alveolar soft part sarcoma featured by TFE3 fusion with primary lesion on left thigh and distal brain metastasis, achieved partial response after three months of pazopanib treatment.

Conclusions: The preliminary data from a small cohort of Chinese sarcoma patients indicated the value of integrative genomic profiling combining both DNAseq and RNAseq in sarcoma diagnosis and potential treatment implications.

_____________________________________________________

Yosef Landesman, Ph.D.
President & Cancer Research Director
Cure Alveolar Soft Part Sarcoma International (iCureASPS)
e-mail: landesmany@yahoo.com