Advanced Sarcoma
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ESMO Open ◽  
2021 ◽  
Vol 6 (5) ◽  
pp. 100249
Author(s):  
J.H. Kim ◽  
S.H. Kim ◽  
M.K. Jeon ◽  
J.E. Kim ◽  
K.H. Kim ◽  
...  

2021 ◽  
Author(s):  
Akash Mitra ◽  
Neeta Somaiah ◽  
Anthony P. Conley ◽  
Behrang Amini ◽  
Heather Lin ◽  
...  

2021 ◽  
Vol 14 (7) ◽  
pp. e243243
Author(s):  
Joshua Christy ◽  
Emad Kandah ◽  
Kavitha Kesari ◽  
Venkatasiva Peram

Non-Hodgkin’s lymphoma (NHL) presenting as a soft tissue sarcoma is rare, occurring at a rate of 0.11%. Peripheral T-cell lymphomas comprise 4% of all NHLs. We report the case of a 49-year-old Caucasian man who presented with a mass in the medial aspect of the thigh. Ultrasound showed a complex subcutaneous mass. MRI demonstrated a superficial complex skeletal mass affecting the sartorius muscle with other lesions involving the femur and the gluteus maximus. Positron emission tomography-computed tomography (PET-CT) showed diffuse pulmonary metastases with no involvement of nodes, liver, spleen with high suspicion of advanced sarcoma. Core biopsy revealed a T-cell NHL, and staining was positive for anaplastic lymphoma kinase. The patient received six cycles of cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone. Repeat PET-CT showed reduction in the mass, with no fluorodeoxyglucose-avid uptake. Latest MRI showed near-normal intensity. Further PET-CTs determine disease remission or progression.


2021 ◽  
Author(s):  
Jean-Yves Blay

Achieving a balance between long-term efficacy and good quality of life (QoL) is the main goal of treatment for patients with advanced soft tissue sarcoma, some of whom experience prolonged survival without progression. An awareness of the challenges particular to this complex set of diseases can help preserve patient QoL during treatment. Histology is among the main factors to consider when selecting treatment in advanced disease. Close attention to the toxicity profiles of available regimens is of particular importance, especially in more advanced lines where the population is usually more vulnerable. Surgical outcomes are significantly better in patients managed with expert care, and early referral to sarcoma reference centers is key to improving survival and QoL.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3073-3073
Author(s):  
Sant P. Chawla ◽  
Victoria S. Chua-Alcala ◽  
Jasgit C. Sachdev ◽  
David S. Wages ◽  
David D. Stenehjem ◽  
...  

3073 Background: Lysine-specific demethylase 1 (LSD1) is an epigenetic enzyme that is aberrantly expressed in many solid tumors. High levels of LSD1 expression are often correlated with poor patient prognosis due to LSD1’s role in cancer cell proliferation, metastasis, and chemoresistance. Seclidemstat is a novel, selective, reversible and oral LSD1 inhibitor capable of inhibiting both LSD1’s catalytic and scaffolding functions. We report preliminary efficacy in AST from an ongoing phase 1 trial. Methods: SALA-003-AC19 (NCT03895684) is a phase 1 trial of single agent SP-2577 in pts with AST. All pts had progressive disease (PD) at time of study entry. Pts received oral SP-2577 twice a day under fasting condition, in 28-day cycles (C). The primary objective is safety and tolerability. Secondary objectives are to determine maximum-tolerated dose, preliminary efficacy, pharmacokinetics, and pharmacodynamics. Results: As of December 30, 2020, 19 pts with AST (10 sarcoma, 2 prostate, 2 ovarian, 2 pancreatic, 1 renal, 1 cervical, 1 breast) were enrolled. Pts received escalating doses of SP-2577 from 150 to 600 mg BID and the dose escalation is ongoing. The median age was 63 years (range, 21–79). 42% were male, and pts had received a median of 4 (range, 1–8) prior systemic therapies. The most common (>5%) grade 3 treatment-related adverse events were GI related including diarrhea (5.3%) and abdominal pain (5.3%). No grade 4 events were reported and there were no treatment-related deaths. Safety data will be presented after completion of phase 1. Three pts had at least one dose reduction. Among the 13 pts who were evaluable for response at end of C2, 7 pts (54%) had best response of stable disease (SD) with median time to progression (TTP) of 4.3 months (range, 2.1–11.5). Four of the 7 pts had genetic abnormalities that may demonstrate increased sensitization to SP-2577 according to preclinical studies. Characteristics of 7 pts with SD at C2 and beyond are shown in the table. Conclusions: Seclidemstat has shown activity among advanced sarcoma pts with a manageable safety profile. The dose escalation is ongoing and preliminary clinical data supports further exploration in FET-translocated sarcoma as single agent and in combination therapy. Clinical trial information: NCT03895684. [Table: see text]


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11567-11567
Author(s):  
Neal Shiv Chawla ◽  
Ted Kim ◽  
Travis Sherman ◽  
Jonathan Dang ◽  
Victoria S. Chua ◽  
...  

11567 Background: Combination trabectidin (T) and nivolumab (N) has been shown to be a safe and effective therapy in soft tissue sarcoma (STS). Intratumoral injection of talimogene laherparepvec (TVEC) has a local oncolytic effect, and increases immune response via enhanced recruitment of antigen presenting cells, and thereby cytotoxic immune response. This study aims to determine if the addition of TVEC to combination trabectedin and nivolumab is effective and safe in advanced sarcoma. Methods: Eligible patients include patients ≥ 18 years of age with locally advanced unresectable or metastatic STS, measurable disease by RECIST v1.1, and at least one accessible tumor for TVEC intratumoral injection. N (3 mg/kg i.v. q 2 weeks), T (1.2 mg/m2 i.v. q 3 weeks) and TVEC (1x10e8 PFU/ml q 2 weeks depending on tumor size) were administered. A test dose of TVEC (1x10e6 PFU/ml) was initially given, followed three weeks later by full dose TVEC. Primary endpoint: Progression-free survival (PFS); Secondary endpoints: (1) Best overall response during treatment period, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 9, and 12 months, (4) Incidence of conversion from unresectable to resectable tumor, and (5) Incidence of treatment-related adverse events. Interim. Results: There were 36 evaluable subjects under the Modified Intention-to-Treat (MITT) population, having completed the first cycle of TNT and a CT or MRI scan at the 6-week follow-up period. The most common histological subtypes include leiomyosarcoma (9), liposarcoma (5), spindle cell sarcoma (3), pleomorphic sarcoma (2), Ewing’s sarcoma (2), and other (5). Median number of prior lines of therapy was 4 (range 1-8). Best Overall Response by RECIST v1.1 = 3 PR, 27 SD, 5 PD. One patient, with previously unresectable disease was taken for resection and was found to have 100% necrosis on surgical pathology. Disease control rate (CR+PR+SD) was 86.1%. The median PFS was 5.5 (range: 1-18) months; 6-month PFS rate: 62.1%. Median PFS on therapy immediately preceding this trial was 2.0 months (range = 1-14 months). There were 47 evaluable subjects for OS analysis under the Intention-to-Treat (ITT) population having received at least one dose of T and N. The median OS was 9.0 (range 0-20) months; 6-month OS rate: 73%. Safety analysis: There were 47 evaluable subjects under the ITT population. 28% of these patients experienced ³1 SAE. The most common grade 3/4 TRAEs include anemia (12), increased ALT (8), fatigue (4), thrombocytopenia (4), neutropenia (4). There were no grade 3/4 TVEC injection site reactions. 22% of patients in the MITT cohort remain on study. Conclusions: These results suggest that combination therapy with TNT appears to be as effective as standard therapy, with no new safety signals seen. Furthermore, median PFS exceeded that of the immediately preceding lines of therapy in this heavily pre-treated cohort. As data matures, further data will be reported. Clinical trial information: NCT03886311.


2021 ◽  
Author(s):  
Qiang Yan ◽  
Xinhui Du ◽  
Liangyu Guo ◽  
Weitao Yao

Abstract Background: Patients with advanced sarcomas have a dismal prognosis with few effective therapies. Previous research has demonstrated the efficacy of anlotinib in the treatment of advanced sarcomas. However, there are few relevant clinical studies, and the efficacy of anlotinib varies among sarcomas of different subtypes. Therefore, more clinical studies are needed to explore the efficacy of anlotinib in different subtypes of sarcomas. This study assessed the efficacy and safety of anlotinib monotherapy in the treatment of advanced sarcoma. Methods: Data from 45 advanced sarcoma patients who received anlotinib monotherapy at Affiliated Cancer Hospital of Zhengzhou University between June 2018 and February 2021 were retrospectively analyzed, including 5 cases of osteosarcoma and 40 cases of soft tissue sarcoma(STS). According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, we evaluated objective response rates (ORR) and disease control rates (DCR) at 3 months, as well as overall ORR and DCR, and calculated progression-free survival(PFS), and then evaluated treatment-related adverse events (AEs). Results: 44 patients were evaluated for efficacy and 45 for treatment-related AES. The ORR and DCR after 3 months were 6.82% and 81.82% respectively. At the end of follow-up, the overall ORR was 2.27%, the total DCR was 27.27%, and the median progression-free survival (m-PFS) was 5.71 months. Among them, the m-PFS of alveolar soft tissue sarcoma (ASPS) was 8.07 months, which was significantly longer than that of other subtypes of sarcoma (P=0.025). The most common adverse events were hypothyroidism (increased TSH) (17.8%), anemia (15.6%), fatigue (11.1%), loss of appetite (11.1%), decreased liver function (11.1%), leukopenia (8.9%) and hand-foot syndrome (8.9%). After treatment, 5 patients developed grade 3 AES, including decreased liver function (4.4%), hypertension (2.2%), proteinuria (2.2%), fatigue (2.2%), and loss of appetite (2.2%). One patient had severe myelosuppression and a significant decrease in white blood cells and platelets. It is worth noting that the PFS of patients with hand-foot syndrome after treatment was significantly longer than that of patients without hand-foot syndrome (P < 0.05). Conclusion: Anlotinib is effective in the treatment of sarcoma, especially in ASPS, Synovial sarcoma (SS) and Fibrosarcoma (FS), and its toxicity is controllable. In addition, the occurrence of hand-foot syndrome after treatment may be related to a good prognosis. However, large sample and prospective studies are needed to confirm it.


2021 ◽  
Vol 9 (2) ◽  
pp. e001696
Author(s):  
Yi Que ◽  
Xiao-Long Zhang ◽  
Ze-Xian Liu ◽  
Jing-Jing Zhao ◽  
Qiu-Zhong Pan ◽  
...  

BackgroundThe advent of immune checkpoint therapy has been a tremendous advance in cancer treatment. However, the responses are still insufficient in patients with soft tissue sarcoma (STS). We aimed to identify rational combinations to increase the response to immune checkpoint therapy and improve survival.MethodsWhole-exome sequencing (WES) was performed in 11 patients with liposarcoma. Somatic copy number alterations (SCNAs) were analyzed at the gene level to identify obvious amplification patterns in drug-target genes. The expression and prognostic value of class I histone deacetylases (HDACs) was evaluated in 49 patients with sarcoma in our center and confirmed in 263 sarcoma samples from The Tumor Cancer Genome Atlas (TCGA) database. Q-PCR, flow cytometry and RNA-seq were performed to determine the correlations between class I HDACs, chidamide and PD-L1 in vitro and in vivo. The efficacy of combining chidamide with PD-1 blockade was explored in an immunocompetent murine model and a small cohort of patients with advanced sarcoma. Western blot, ChIP assay and dual luciferase assessment were applied in the mechanistic study.ResultsThe HDAC gene family was frequently amplified in STS. SCNAs in the HDAC gene family were extensively amplified in 8 of 11 (73%) patients with liposarcoma, based on a drug-target gene set, and we verified amplification in 76.65% (197/257) of cases by analyzing TCGA sarcoma cohort. Class I HDAC expression is associated with a poor prognosis for patients with STS, and its inhibition is responsible for promoting apoptosis and upregulating of programmed cell death ligand 1 (PD-L1). The HDAC class I inhibitor chidamide significantly increases PD-L1 expression, increased the infiltration of CD8+ T cells and reduced the number of MDSCs in the tumor microenvironment. The combination of chidamide with an anti-PD-1 antibody significantly promotes tumor regression and improves survival in a murine model. Moreover, chidamide combined with the anti-PD-1 antibody toripalimab is effective in patients with advanced and metastatic sarcoma, and the side effects are tolerable. Mechanistically, chidamide increases histone acetylation at the PD-L1 gene through the activation of the transcriptional factor STAT1.ConclusionsThe combination of chidamide and anti-programmed cell death 1 (PD-1) therapy represents a potentially important strategy for STS.


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