Efficacy and safety of anlotinib in advanced soft tissue sarcoma: results from one of multi-centers in a phase IIB trial (ALTER0203).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e22518-e22518 ◽  
Author(s):  
Lina Tang ◽  
Yonggang Wang ◽  
Jianjun Zhang ◽  
Wenxi Yu ◽  
Yujing Huang ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Regional Differences ◽  
Soft Part ◽  
Angiogenesis Inhibitor ◽  
Progression Free Survival ◽  
Clear Cell Sarcoma ◽  
Gamma Glutamyl Transferase ◽  
Efficacy And Safety ◽  
Glutamyl Transferase

e22518 Background: There is no standard therapy for soft tissue sarcoma (STS) patients progressing after first-line chemotherapy. Anlotinib significantly prolonged PFS in advanced STS patients in the earlier results of ALTER0203. In view of regional differences, we further analysis results from Affiliated Sixth People’s Hospital, Shanghai Jiaotong University, one center in this IIB trial. Methods: Patients aged from 18 to 70 with advanced STS, progressing after anthracycline-based chemotherapy (not adapted to alveolar soft part sarcoma (ASPS) and clear cell sarcoma (CSC)), angiogenesis inhibitor naive, at least one measurable lesion according to RECIST 1.1, were eligible. Patients were randomised in a 2:1 ratio to receive anlotinib (12 mg per day 2 weeks on and 1 week off) or placebo. Primary endpoint was progression free survival (PFS). Secondary endpoints were overall response rate (ORR), disease control rate (DCR). Results: This center of ALTER0203 enrolled 48 eligible patients who received either anlotinib (n = 32) or placebo (n = 16). Leiomyosarcoma (LMS) (13/48), ASPS (12/48), synovial sarcoma (SS) (11/48) were major subtypes. The median PFS was 1.57 months (95% CI: 1.19-1.95) for placebo versus 6.27 months (95% CI: 1.89-10.65) for anlotinib ( P= 0.009). ORR was 0% (0/16) for placebo versus 18.75% (6/32) for anlotinib ( P= 0.16); DCR was 18.75% (3/16) for placebo versus 56.25% (18/32) for anlotinib ( P= 0.02). The most common adverse events (AEs) were hypertension, elevated TSH, hypertriglyceridaemia (HTG). The most common Grade ≥3 AEs were menstrual disorder, hypertension, gamma glutamyl transferase (GGT) elevation and lipase elevation. Conclusions: The efficacy and safety of anlotinib is further confirmed in advanced STS patients regarding regional differences. Clinical trial information: NCT02449343. [Table: see text]

Efficacy and safety of anlotinib plus TQB2450 in patients with advanced soft tissue sarcoma: A multicenter, single armed, phase 1b trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11547-11547
Author(s):  
Jiayong Liu ◽  
Zhengfu Fan ◽  
Wei Guo ◽  
Tian Gao ◽  
Shu Li ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Kinase Inhibitor ◽  
Soft Part ◽  
Epithelioid Sarcoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Phase 1B ◽  
Anthracycline Chemotherapy

11547 Background: Anlotinib, a multitargeted tyrosine kinase inhibitor, had been prove to be effective for the treatment of advanced or metastatic soft tissue sarcoma(STS) faild anthracycline chemotherapy. With the lack of prospective data of combination of PDL-1 inhibitor and antiangiogenic agent, we designed a phase 1b study to investigated the efficacy and safety of anlotinib plus TQB2450 in patients with STS. Methods: Eligible patients (age 18-70, ECOG 0-1, with histopathologically confirmed advanced STS, at least one measurable lesion according to RECIST 1.1, and previously received front-line anthracycline chemotherapy) were included and received anlotinib (12mg qd, D1-14, 21d/cycle) plus TQB2450 (1200 mg, IV, D1, 21d/cycle) until disease progression or intolerable toxicities.The primary endpoint was objective response rate (ORR), secondary endpoints included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR). Results: From January 2019 to January 2021, 30 pts were enrolled1, 12 alveolar soft part sarcoma and 18 others (7 synovial sarcoma, 4 leiomyosarcoma, 5 undifferentiated pleomorphic sarcoma, 1 fibrosarcoma and 1 epithelioid sarcoma). ORR by RECIST was 36.7%, DCR was 83.3%, 11/30 pts had PR, 14/30 (46.7%) had SD, 5/30 (16.7%) PD. Median PFS was 9.6 m in all pts and 4.9m. in non-ASPS, respectively. Median OS in non-ASPS was 10.27m, while mOS in all pts and both mPFS and mOS in ASPS had not been reached. Notably, to ASPS pts, ORR was 75%, and DCR was 100%. The most common 1-2 grade treatment-related adverse reaction (TRAE) was hypothyroidism (19/30,63.3%)，hypercholesterolemia (16/30, 53.3%) and hypertriglyceridemia (16/30, 53.3%), the most common ≥3 grade TRAEs were hypertriglyceridemia (3/30, 10%). 6 SAE (20%) occurred, including 2 pneumothorax, 1 Immune associated hapatic injury, 1 hypotension, 1 Immune myocarditis and 1 diabetic ketoacidosis. Conclusions: The combination of anlotinib and TQB2450 showed promising activity in second-line treatment of advanced STS, especially in ASPS, with well tolerance and acceptable toxicity.

scholarly journals PD-1 blockade using pembrolizumab in adolescent and young adult patients with advanced bone and soft tissue sarcoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3060-3060 ◽  
Author(s):  
Tahlia Scheinberg ◽  
Anna Lomax ◽  
Martin HN Tattersall ◽  
David Morgan Thomas ◽  
Geoffrey Brian McCowage ◽  
...  
Keyword(s):  
Young Adult ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Soft Part ◽  
Initial Response ◽  
Clear Cell Sarcoma ◽  
Median Number ◽  
Adolescent And Young Adult ◽  
Improved Outcomes ◽  
Ecog Ps

3060 Background: Sarcomas represent 10–15% of cancers in adolescent and young adult (AYA) patients, and survival for those with metastatic disease or after relapse is poor. Immunotherapy with checkpoint inhibition has improved outcomes in multiple tumour types, but there are limited data on the efficacy of immunotherapy in advanced sarcomas, particularly within the AYA population. Methods: We retrospectively reviewed AYA patients with advanced bone and soft tissue sarcoma who received self-funded pembrolizumab at Chris O’Brien Lifehouse and Children’s Hospital Westmead. Initial response was evaluated after cycle three or four using RECIST v1.1 criteria. Results: Fourteen AYA patients with sarcoma received pembrolizumab 2mg/kg IV every 3 weeks from May 2015 to December 2016. Median age was 24 (14 – 35), male to female was 7:7, ECOG PS was 0 – 1 in 6 patients, 2 in 6 patients and 3 – 4 in 2 patients. Malignancy type included three patients with osteosarcoma (OS), five patients with Ewing sarcoma (ES), two patients with synovial sarcoma (SS), two patients with alveolar soft part sarcoma (ASPS), and one patient with each of embryonal rhabdomyosarcoma (RMS) and clear cell sarcoma (CCS). The median number of pembrolizumab doses was four (range 1 – 16), with one patient still receiving treatment at the time of last follow up. Treatment was generally very well tolerated with no G3-4 toxicity. One patient with ES had an excellent, sustained response; of the two patients with ASPS one had a radiological partial response with an excellent clinical response and one patient achieved stable disease. Three patients (two ES, one RMS) died of disease prior to first scheduled assessment and thus their response was not evaluable. The remaining 8 patients had progressive disease. Conclusions: Our data suggest further evaluation of the role of pembrolizumab in AYA patients with advanced sarcoma is warranted.

scholarly journals A Retrospective Analysis of the Efficacy and Safety of Anlotinib in the Treatment of Advanced Sarcoma

2021 ◽  
Author(s):  
Qiang Yan ◽  
Xinhui Du ◽  
Liangyu Guo ◽  
Weitao Yao
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Liver Function ◽  
Adverse Events ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Hand Foot Syndrome ◽  
Loss Of Appetite ◽  
Advanced Sarcoma

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.

Randomized, Phase II Study of the Thrombospondin-1-Mimetic Angiogenesis Inhibitor ABT-510 in Patients With Advanced Soft Tissue Sarcoma

2008 ◽  
Vol 26 (34) ◽  
pp. 5583-5588 ◽  
Author(s):  
Laurence H. Baker ◽  
Eric K. Rowinsky ◽  
David Mendelson ◽  
Rod A. Humerickhouse ◽  
Raymond A. Knight ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Day Treatment ◽  
Single Agent ◽  
Objective Response ◽  
Angiogenesis Inhibitor ◽  
Progression Free Survival ◽  
Study Results

Purpose Sarcomas are among the most proangiogenic malignancies in preclinical models. Phase I study results for ABT-510, which inhibits angiogenesis via a novel thrombospondin-mimetic mechanism, suggested activity in soft tissue sarcoma (STS) patients. This phase II study further evaluated the safety and efficacy of ABT-510 in advanced STS patients. Patients and Methods Patients with metastatic or unresectable STS were randomly assigned to treatment with one of two ABT-510 dose schedules (20 mg once a day [20 mg], n = 42; or 100 mg twice a day [200 mg], n = 46), which were self-administered subcutaneously in 28-day treatment periods. End points included progression-free survival (PFS), objective response rate (ORR), overall survival (OS), and safety. Results Median PFS for the 20-mg arm was 94 days, with 4- and 6-month PFS rate estimates of 42% and 24%, respectively. Median PFS for the 200-mg arm was 64 days, with 4- and 6-month PFS rate estimates of 41% and 32%, respectively. Although only one objective response was noted, stable disease was observed in 52% (20 mg) and 48% (200 mg) of patients. Median OS was 431 days (20 mg) and 295 days (200 mg). ABT-510 was well tolerated. Rare treatment-related grade 3 or 4 adverse events were one event each of hypotension, deep vein thrombosis, and hypophosphatemia. ABT-510 pharmacokinetics were dose proportional, time independent, and consistent with those in previous studies. Conclusion ABT-510 had a favorable safety profile, and the rate of disease control and OS times were encouraging. However, with low ORR and lack of dose response, the study failed to yield compelling evidence of strong single-agent activity in STS.

scholarly journals Efficacy and safety of anlotinib, a multikinase angiogenesis inhibitor, in combination with epirubicin in preclinical models of soft tissue sarcoma

2020 ◽  
Vol 9 (10) ◽  
pp. 3344-3352
Author(s):  
Zhi‐Ming Wang ◽  
Shi‐Long Zhang ◽  
Hua Yang ◽  
Rong‐Yuan Zhuang ◽  
Xi Guo ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Angiogenesis Inhibitor ◽  
Efficacy And Safety ◽  
Preclinical Models

scholarly journals Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series

2021 ◽  
Vol 28 (1) ◽  
pp. 813-817
Author(s):  
Arielle Elkrief ◽  
Suzanne Kazandjian ◽  
Thierry Alcindor
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Objective Response ◽  
Case Series ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
First Line ◽  
Pleomorphic Sarcoma ◽  
Line Setting

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.

scholarly journals Stereotactic Body Radiotherapy for Metastatic and Recurrent Soft Tissue Sarcoma

2020 ◽  
Author(s):  
Xiaoyao Feng ◽  
Jing Li ◽  
Aomei Li ◽  
Han Zhou ◽  
Xixu Zhu ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Hematogenous Metastasis ◽  
Invasive Growth ◽  
Free Survival ◽  
Grade 3 ◽  
Clinical Transformation

Abstract BackgroundSoft tissue sarcoma（STS） is a malignant tumor of highly heterogeneous mesenchymal origin. STS has a biologic pattern and clinical transformation with localized invasive growth and susceptibility to hematogenous metastasis. Metastatic and recurrent soft tissue sarcoma may be treated by local therapeutic options, including surgery and radiation therapy. This study evaluated the safety and efficacy of SBRT for metastatic and recurrent soft tissue sarcoma.MethodsWe performed a retrospective analysis of 37 STS patients with 58 lesions treated with SBRT from 2009-2019 at our institution. We analyze the local control (LC), overall survival (OS), progression free survival (PFS) and toxicity rates of the patients.ResultThe median follow-up was 20 months（range 2 to 120 months）. One and two year LC rates were 75.3% and 55.2% [95% confidence interval (CI) 20–25 months]. Median OS was 24 months and the survival rates were 66.6%, 45% and 26.6% at 1, 2 and 3-year after SBRT. Median PFS were 11months (95% CI 8–18 months). No acute or chronic grade ≥ 3 toxicity was observed.ConclusionsIn patients with metastatic and recurrent STS, LC, OS and PFS were higher than expected. SBRT should be a proper treatment option for STS.

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