SM Journal of Sarcoma Research Gr up SM How to cite this article Chawla SP, Sankhala KK, Ravicz JR, Kang GE, Liu S, Assudani N, et al. Clinical Experience with Combination Chemo-/Immunotherapy using Trabectedin and Nivolumab for Advanced Soft Tissue Sarcoma. SM J Sarcoma Res. 2018; 2(1): 1009. Introduction Sof tissue sarcoma is a rare heterogenous group of malignancies that arise from the mesenchymal tissue. It comprises about 1% of all adult cancers. Te American Cancer Society estimates 13,040 new cases of sof tissue sarcomas and 5,150 deaths due to sof tissue sarcomas in the United States for the year 2018 [1]. Te most prevalent types of sarcoma in adults are undiferentiated pleomorphic sarcoma (formerly called malignant fbrous histiocytoma), liposarcoma, and leiomyosarcoma. Certain types occur more ofen in certain areas of the body, e.g., leiomyosarcoma is the most commonly found abdominal sarcoma, while liposarcoma and undiferentiated pleomorphic sarcoma are most likely seen in legs [2]. Surgical resection is the treatment of choice for localized disease, with radiation therapy given as frst-line treatment for unresectable cases. However, about half the high-grade cases tend to recur [3]. For several years, sof tissue sarcoma management was limited to doxorubicin and/or ifosfamide, with an estimated median survival of 8-13 months, as per the results of randomized studies conducted over the last 2 decades [4-7]. Targeted therapies like pazopanib (Votrient®) showed a signifcant, but modest beneft in Progression Free Survival (PFS) for patients with locally advanced unresectable or metastatic sof tissue sarcoma [8]. Te USFDA approval of trabectedin (Yondelis®) in 2015, showed further promise for improving the quality of life and progression free survival of patients with sof tissue sarcoma [2,9-13]. Trabectedin (ET-743), a marine derived natural alkaloid, has a complex mechanism of action that not only afects key cell biology processes in tumour cells but also the tumour microenvironment via direct efects on tumour-associated macrophages and tissue-resident histiocytes [11,12,14]. Research Article Clinical Experience with Combination Chemo-/Immunotherapy using Trabectedin and Nivolumab for Advanced Sof Tissue Sarcoma Sant P Chawla 1 , K Kumar Sankhala 2 , Joshua R Ravicz 1 , Grace E Kang 1 , Seiya Liu 3 , Nupur Assudani 1 , Shiva Sreenath Andrali 1 , Nathan Stumpf 1 , Bryan C Leong 1 , Seth Kim 1 , Suzan Arasheben 1 ,William Tseng 4 , Don A Brigham 1 and Erlinda M Gordon 1 * 1 Cancer Center of Southern California/Sarcoma Oncology Center, USA 2 Cedars-Sinai Medical Center, USA 3 Harvard University, USA 4 USC Keck School of Medicine, USA Article Information Received date: Apr 08, 2018 Accepted date: Apr 19, 2018 Published date: May 16, 2018 *Corresponding author Erlinda M Gordon, Cancer Center of Southern California/Sarcoma Oncology Center, USA, Suite 414, Santa Monica CA, 90403, Email: erlinda.gordon@gmail.com Distributed under Creative Commons CC-BY 4.0 Keywords Alkylating Agent; PD-1 Inhibitor; Chemo-/Immunotherapy; Soft Tissue Sarcoma; Immune Checkpoint Inhibitor Abstract Immune checkpoint inhibitors revive pre-existing immune responses that are suppressed in cancer. To restore innate tumour surveillance that is lost in cancer patients, a tumoricidal agent may have synergistic activity with certain immune checkpoint inhibitors. Herein, we report on our clinical experience using two FDA-approved drugs, trabectedin, a marine derived natural alkaloid with pro-apoptosis and immune modulator properties, in combination with nivolumab, a PD-1 immune checkpoint inhibitor, in advanced Soft Tissue Sarcoma (STS). Twenty-eight heavily pre-treated STS patients received trabectedin (1.5 mg/m 2 Continuous Intravenous Infusion, CIV, for 24 hours) every 3 weeks, and nivolumab (3 mg/kg IV over 30 minutes) every 2 weeks. Retrospective analysis of safety/toxicity was conducted using the NIH/NCI CTCAE v.4.03. Tumour responses were assessed by RECIST v1.1 and irRECIST. Histologic subtypes in 28 patients include undifferentiated pleomorphic sarcoma (UPS; n=7), myofbroblastic sarcoma (n=1), leiomyosarcoma (n=6), synovial sarcoma (n=4), liposarcoma (n=6), chondrosarcoma (n=2), and Ewing sarcoma (n=2). All patients had metastatic disease and a median of 4 lines of prior chemotherapy. Safety analysis (n=28): Grade 3 treatment emergent adverse events include anaemia (n=2), fatigue (n=1), decreased platelet count (n=1), decreased granulocyte count (n=1) and increased creatine kinase (n=1). Effcacy analysis (n=22): Twenty-two patients were followed for at least 6 months and their results are reported here. There were 4 partial responses (UPS=1, myxoid liposarcoma=1, chondrosarcoma=1, leiomyosarcoma=1), 12 stable disease and 6 progressive disease, with best overall response rate of 18.2%, median progression free survival (PFS) of >45.4 weeks (range: 10->95 weeks), median Overall Survival (OS) of >66.5 weeks (10->95 weeks), 6 month PFS rate of 68.2%, and 6 month OS rate of 95.4%. Taken together, the data suggest that paired administration of trabectedin and nivolumab is safe, and that this chemo-/immuno- therapy approach has synergistic activity that can lead to improved clinical outcomes.