Abstract CT083: Apatinib for advanced bone and soft tissue sarcomas in stage IV: Focus on efficacy and safety

e22532 Background: There is no standard treatment for stage IV soft tissue tumor (STS) after the failure of Adriamycin-based chemotherapy. This opening, single-arm, multi-center phase II study (NCT03120846) assessed the efficacy and safety of Apatinib (YN968D1), a new tyrosine kinase inhibitor that targets VEGFR-2, for patients with stage IV soft tissue tumor after the failure of chemotherapy. Methods: Between September 2015 and February 2018, we recruited 42 patients with stage IV STS who had failed chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were progression-free survival rate (PFR), objective response rate (ORR), and disease control rate (DCR) at week 12. Secondary endpoint was overall survival (OS). Treatment-related adverse effects (AEs) were evaluated. Results: Patients (19 men, 23 women; 14-83 years, average age: 47.67years) received 500 mg apatinib on Days 1–28 of 4-week cycles (median 5.7 cycles; range: 0–23 cycles). Median follow-up was 9 months (range: 1–28 months). We assessed 42 patients for AEs and 38 for efficacy. At 12 weeks, PFR was 70% and the ORR was 26.32% (10/38) and DCR was 86.84% (33/38). For the overall responses, the ORR was 23.68% (9/38) and DCR was 57.89% (22/38). The median PFS was 7.87 months and median OS was 17.55 months. The top AEs included hypertension ( n= 18, 42.86%), hand-foot-skin reaction ( n= 15, 35.71%), Apositia (13, 30.95%), and proteinuria ( n= 11, 26.19%). No patients had grade-4 AEs. 11 (26.19%) had grade-3 AEs. 2 patients (4.76%) quit because the AE. Notably, the 26 patients (61.90%) who suffered hypertension, hand-foot-skin reaction or proteinuria had significantly longer OS than those without these AEs (20.94 vs. 8.93 months; Log Rank (Mantel-Cox) = 12.94, P= 0.0003). Conclusions: Apatinib is effective and well tolerated in patients with advanced soft tissue sarcomas. The adverse events hypertension, hand-foot-skin reaction, or proteinuria may indicate a favorable prognosis, representing a novel finding in STS patients. Clinical trial information: NCT03120846.

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Efficacy and Safety of Endostar®Combined with Chemotherapy in Patients with Advanced Soft Tissue Sarcomas

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2013.14.7.4255 ◽

2013 ◽

Vol 14 (7) ◽

pp. 4255-4259 ◽

Cited By ~ 8

Author(s):

Lu-Ping Zhang ◽

Xing-Yun Liao ◽

Yan-Mei Xu ◽

Lv-Jun Yan ◽

Gui-Fang Yan ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcomas ◽

Efficacy And Safety

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Multicenter, triple-arm, single-stage, phase II trial to determine the efficacy and safety of everolimus (RAD001) in patients with refractory bone or soft tissue sarcomas including GIST.

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.10038 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. 10038-10038 ◽

Cited By ~ 12

Author(s):

S. Richter ◽

D. Pink ◽

P. Hohenberger ◽

H. Schuette ◽

P. G. Casali ◽

...

Keyword(s):

Soft Tissue ◽

Phase Ii ◽

Phase Ii Trial ◽

Soft Tissue Sarcomas ◽

Single Stage ◽

Efficacy And Safety

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Multicenter Phase 3 Study of Efficacy and Safety of Aldoxorubicin Versus Investigator'S Choice for Relapsed/Refractory Soft Tissue Sarcomas

Annals of Oncology ◽

10.1093/annonc/mdu354.50 ◽

2014 ◽

Vol 25 ◽

pp. iv510

Author(s):

S.P. Chawla ◽

K. Sankhala ◽

S. Wieland ◽

D. Levitt

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcomas ◽

Efficacy And Safety ◽

Phase 3 ◽

Multicenter Phase

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Recombined humanized endostatin (Endostar) combined with chemotherapy for advanced bone and soft tissue sarcomas in stage IV

Oncotarget ◽

10.18632/oncotarget.13545 ◽

2016 ◽

Vol 8 (22) ◽

pp. 36716-36727 ◽

Cited By ~ 5

Author(s):

Peipei Xing ◽

Jin Zhang ◽

Zhao Yan ◽

Gang Zhao ◽

Xubin Li ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcomas ◽

Stage Iv

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Efficacy and Safety of Anlotinib Combined with Liposomal Doxorubicin Followed by Anlotinib Maintenance in Metastatic Soft Tissue Sarcomas

Cancer Management and Research ◽

10.2147/cmar.s286322 ◽

2021 ◽

Vol Volume 13 ◽

pp. 1009-1016

Author(s):

Zhiyong Liu ◽

Weitao Yao ◽

Yao Zhao ◽

Oufei Liu ◽

Peng Zhang ◽

...

Keyword(s):

Soft Tissue ◽

Liposomal Doxorubicin ◽

Soft Tissue Sarcomas ◽

Efficacy And Safety

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Real-world data of a cohort of patients with soft tissue sarcoma in a single institution of Colombia.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e19259 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e19259-e19259

Author(s):

Luis Eduardo Pino ◽

Ivan Camilo Triana ◽

Aylen Vanessa Ospina Serrano ◽

Javier Segovia ◽

Diana Carolina Hennessey

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Real World ◽

Ewing’S Sarcoma ◽

Ewing's Sarcoma ◽

Soft Tissue Sarcomas ◽

Stage Iv ◽

University Hospital ◽

Single Institution ◽

Pleomorphic Sarcoma

e19259 Background: Soft Tissue Sarcomas (STS) are a group of neoplasm with huge histological diversity and biological behaviors. They have a low prevalence and lack of data, especially in Colombia where there is no specific report of this disease. The objective of this study is to describe clinical characteristics and outcomes of patients with soft tissue sarcoma at Fundación Santafe, a university hospital located in Bogotá. Methods: This is an observational study of a cohort of soft tissue sarcoma patients treated at a single institution with a follow-up of 4 years (2015 - 2019). Clinical, molecular and epidemiological variables were registered, and overall survival was calculated for stage IV sarcomas. For the survival analysis a Kaplan Meier model was used. Results: Twenty-four patients were included. The histologies reported were: Pleomorphic sarcoma 25.0%, Ewing's sarcoma 20.8%, liposarcoma 16.7%, chondrosarcoma 8.3%, leiomiosarcoma 8.3%, synovial sarcoma 8.3%, soft part alveolar sarcoma 8.3%, and dermatofibrosarcoma protuberans 4.3%. OSm for the whole stage IV group was: 30.22m, according to subtypes OSm was: Ewing's sarcoma 37.13 OSm, liposarcoma 11 OSm, chondrosarcoma 12.3 OSm. Only 3 of the cases (2 Ewing's sarcoma and 1 alveolar sarcoma) had multigenic platform information. In these cases, main mutations in BCL2, SOX9, SATB2 and TFE3 were described. In two of the cases PDL1 expression was done with a negative result ( < 1%) (pleomorphic sarcoma and Ewing's sarcoma). Ifosfamide and anthracyclines was the most frequent chemotherapy regimen used, but in two of the cases checkpoint inhibitors were initiated. Conclusions: This real-world cohort of STS have a similar clinical and epidemiological distribution to historic cohorts, but our OSm for Ewing's sarcoma stage IV is longer than reported, even with a case of complete remission after consolidation with autologous bone marrow transplant. Other histologies had a worse prognosis with a less than 12 m OSm. Genomic data were scarce and useless for directed therapies or immunotherapy as usual in STS. [Table: see text]

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Delayed use of eribulin in a heavily pretreated liposarcoma patient, previously misdiagnosed as leiomyosarcoma

Future Oncology ◽

10.2217/fon-2019-0596 ◽

2020 ◽

Vol 16 (1s) ◽

pp. 9-13 ◽

Cited By ~ 1

Author(s):

Federica Martorana ◽

Paolo Vigneri ◽

Livia Manzella ◽

Elena Tirrò ◽

Héctor J. Soto Parra

Keyword(s):

Soft Tissue ◽

Adverse Effects ◽

Safety Profile ◽

Clinical Benefit ◽

Soft Tissue Sarcomas ◽

Molecular Profiling ◽

Efficacy And Safety ◽

Substantial Clinical Benefit ◽

Heavily Pretreated ◽

Low Incidence

Due to its low incidence, liposarcoma displays a limited number of therapeutic options. However, eribulin recently received approval for the treatment of advanced liposarcoma patients, progressing to at least two chemotherapy lines. We report herein the case of a man initially diagnosed with a leyomiosarcoma, subsequently reclassified as a dedifferentiated liposarcoma, who received eribulin after he failed several therapy lines. Eribulin provided our patient an 8-month disease control and a substantial clinical benefit with no relevant adverse effects, showing a good efficacy and safety profile despite its delayed employ. Additionally, this case strengthens the pivotal importance of molecular profiling in the management of soft tissue sarcomas.

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Predicting the Efficacy and Safety of TACTICs (Tumor Angiogenesis-Specific CAR-T Cells Impacting Cancers) Therapy for Soft Tissue Sarcoma Patients

Cancers ◽

10.3390/cancers12102735 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2735

Author(s):

Kento Fujiwara ◽

Shigemi Sasawatari ◽

Sho Nakai ◽

Keisuke Imaeda ◽

Seina Nagai ◽

...

Keyword(s):

T Cells ◽

Soft Tissue ◽

Tumor Angiogenesis ◽

Growth Factor Receptor ◽

Soft Tissue Sarcomas ◽

Efficacy And Safety ◽

Normal Tissues ◽

Car T Cells ◽

Car T ◽

New Treatment

Soft tissue sarcomas (STSs) are heterogeneous and aggressive malignancies with few effective therapies available. We have developed T cells expressing a vascular endothelial growth factor receptor 2 (VEGFR2)-specific chimeric antigen receptor (CAR) to establish a tumor angiogenesis-specific CAR-T cells impacting cancers (TACTICs) therapy. In this study, we optimized the manufacturing and transportation of mRNA-transfected anti-VEGFR2 CAR-T cells and collected information that allowed the extrapolation of the efficacy and safety potential of TACTICs therapy for STS patients. Although 5-methoxyuridines versus uridines did not improve CAR-mRNA stability in T cells, the utilization of CleanCap as a 5′ cap-structure extended the CAR expression level, increasing VEGFR2-specific cytotoxicity. Furthermore, 4 °C preservation conditions did not affect the viability/cytotoxicity of CAR-T cells, contrarily to a freeze-thaw approach. Importantly, immunohistochemistry showed that most of the STS patients’ specimens expressed VEGFR2, suggesting a great potential of our TACTICs approach. However, VEGFR2 expression was also detected in normal tissues, stressing the importance of the application of a strict monitoring schedule to detect (and respond to) the occurrence of adverse effects in clinics. Overall, our results support the development of a “first in humans” study to evaluate the potential of our TACTICs therapy as a new treatment option for STSs.

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