advanced sarcoma
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2022 ◽  
Vol 23 (2) ◽  
Author(s):  
Shouq Alzaaqi ◽  
Norifumi Naka ◽  
Kenichiro Hamada ◽  
Naoki Hosen ◽  
Mizuki Kanegae ◽  
...  

2021 ◽  
pp. clincanres.3445.2021
Author(s):  
Nicholas D Klemen ◽  
Sinchun Hwang ◽  
Martina Bradic ◽  
Evan Rosenbaum ◽  
Mark A. Dickson ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Edmund K. Bartlett ◽  
Sandra P. D’Angelo ◽  
Ciara M. Kelly ◽  
Robert H. Siegelbaum ◽  
Charles Fisher ◽  
...  

Treatment options for patients with advanced sarcoma remain limited. Promising responses to checkpoint inhibition have been observed, but responses to single-agent PD-1 inhibition are rare. We report on two patients with multiply recurrent myxofibrosarcoma treated with the combination of regionally administered melphalan (via isolated limb infusion) and pembrolizumab. Both patients had recurrent disease after multiple surgical resections and radiation. Analysis of primary tumors demonstrated microsatellite stable tumors with few mutations. After combination treatment, one patient had a significant partial response of 6 months duration, the second patient had a complete response of 2 years duration. Post treatment biopsies demonstrated immune infiltration into the tumor. These promising responses in patients with multiply recurrent myxofibrosarcoma have prompted the development of an investigator-initiated clinical trial to formally study the combination of regional melphalan and pembrolizumab in a systematic fashion (NCT04332874).


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 ◽  
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. 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.


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