Cancer immunotherapy using trabectedin and nivolumab in advanced soft tissue sarcoma: A retrospective analysis.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 40-40 ◽  
Author(s):  
Erlinda Maria Gordon ◽  
Kamalesh Kumar Sankhala ◽  
Nathan Stumpf ◽  
Joshua Ravicz ◽  
Suzan Arasheben ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Retrospective Analysis ◽  
Progression Free Survival ◽  
Myxoid Liposarcoma ◽  
Synergistic Activity ◽  
Advanced Soft Tissue Sarcoma ◽  
Efficacy Analysis ◽  
Pleomorphic Sarcoma ◽  
Grade 3

40 Background: To restore innate tumor surveillance that is lost in cancer patients, a tumoricidal agent may have synergistic activity with an immune checkpoint inhibitor. Herein, we report on a retrospective analysis of our clinical experience using trabectedin, an alkylating agent, and nivolumab, a PD-1 inhibitor in advanced soft tissue sarcoma. Methods: Twenty previously treated STS patients received trabectedin (1.5 mg/m2 continuous intravenous infusion, CIV, for 24 hours) every 3 weeks, and nivolumab (3 mg/kg IV over 30 minutes) every 2 weeks. Safety/toxicity was analyzed using the NIH/NCI CTCAE v.4.03. Tumor responses were assessed by RECIST v1.1 and immune-related response criteria (irRECIST). Results: Histologic subtypes in 20 patients include undifferentiated pleomorphic sarcoma (UPS; n = 7), leiomyosarcoma (n = 5), synovial sarcoma (n = 2), myxoid liposarcoma (n = 4) and chondrosarcoma (n = 2). All patients had metastatic disease and a median of 4 lines of prior chemotherapy. Safety analysis (n = 20): Grade 3 treatment emergent adverse events include anemia (n = 2), fatigue (n = 1), decreased platelet count (n = 1), decreased granulocyte count (n = 1) and increased creatine kinase (n = 1). Efficacy analysis (n = 17): Seventeen 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), 7 stable disease, and 6 progressive disease, with best overall response rate of 23.5%, median progression free survival (PFS) of > 11.6 months (range: 2.3- > 16.9 months), median overall survival (OS) of > 14.2 months (4.5- > 24.0 months), 6 month PFS rate of 64.7%, and 6 month OS rate of 94.1%. In a Phase 3 study, the median PFS was 4.2 months using trabectedin alone (Demetri et al., 2015). Conclusions: Taken together, the data suggest that paired administration of trabectedin and nivolumab is safe, and that this chemo-/immuno-therapy approach has synergistic activity.

Phase II Study of ET-743 in Advanced Soft Tissue Sarcomas: A European Organisation for the Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group Trial

2005 ◽  
Vol 23 (3) ◽  
pp. 576-584 ◽  
Author(s):  
A. Le Cesne ◽  
J.Y. Blay ◽  
I. Judson ◽  
A. Van Oosterom ◽  
J. Verweij ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Phase Ii ◽  
Median Duration ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Advanced Soft Tissue Sarcoma ◽  
Free Survival ◽  
Grade 3 ◽  
Line Chemotherapy

Purpose This nonrandomized multicenter phase II study was performed to evaluate the activity and safety of Ecteinascidin (ET-743) administered at a dose of 1.5 mg/m2 as a 24-hour continuous infusion every 3 weeks in patients with pretreated advanced soft tissue sarcoma. Patients and Methods Patients with documented progressive advanced soft tissue sarcoma received ET-743 as second- or third-line chemotherapy. Antitumor activity was evaluated every 6 weeks until progression, excessive toxicity, or patient refusal. Results One hundred four patients from eight European institutions were included in the study (March 1999 to November 2000). A total of 410 cycles were administered in 99 assessable patients. Toxicity mainly involved reversible grade 3 to 4 asymptomatic elevation of transaminases in 40% of patients, and grade 3 to 4 neutropenia was observed in 52% of patients. There were eight partial responses (PR; objective regression rate, 8%), 45 no change (NC; > 6 months in 26% of patients), and 39 progressive disease. A progression arrest rate (PR + NC) of 56% was observed in leiomyosarcoma and 61% in synovialosarcoma. The median duration of the time to progression was 105 days, and the 6-month progression-free survival was 29%. The median duration of survival was 9.2 months. Conclusion ET-743 seems to be a promising active agent in advanced soft tissue sarcoma, with no cumulative toxicities. The 6-months progression-free survival observed in advanced soft tissue sarcoma compares favorably with those obtained with other active drugs tested in second-line chemotherapy in previous European Organisation for the Research and Treatment of Cancer trials. The median overall survival was unusually long in these heavily pretreated patients mainly due to the high number of patients who benefit from the drug in terms of tumor control.

Postmarketing observational study of pazopanib in patients with metastatic soft tissue sarcoma in Japan

2020 ◽  
Author(s):  
Yasutomo Teshima ◽  
Satoshi Nomura ◽  
Nobuaki Fukasawa
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Observational Study ◽  
Progression Free Survival ◽  
Free Survival ◽  
Safety And Efficacy ◽  
Efficacy Analysis ◽  
Metastatic Soft Tissue Sarcoma ◽  
Grade 3 ◽  
Observation Period

Abstract Background This study evaluated the safety and efficacy of pazopanib in patients with metastatic soft tissue sarcoma in routine clinical use in Japan. Methods It was a multicentre, centrally registered and uncontrolled observational study in patients who received pazopanib for metastatic soft tissue sarcoma, with an observation period of 1 year after the start of drug administration. The study was conducted at 378 investigational sites in Japan from September 2012 to September 2019. Progression-free survival (PFS) and overall survival (OS) were the efficacy endpoints of the study. Results A total of 1970 patients were enrolled. Of these, 680 with finalized study forms were included in the analysis. Overall, 649 patients were included in the safety analysis set, and 569 were included in the efficacy analysis set. Most of the patients (81.97%) experienced at least one adverse drug reaction (ADR); 22.34% of patients reported serious ADRs and 34.98% of patients experienced grade ≥ 3 ADRs in the safety set. Hypertension (40.37%) and hepatic dysfunction (26.50%) were the two most common ADRs. A total of 262 deaths were reported, of which 12 were due to ADRs. The median PFS was 3.09 months, whereas the median OS was not reached at the end of the 1-year observation period. Conclusions The safety and efficacy profiles in this postmarketing observational study were consistent with prior data and registration clinical trials. No new safety signals were observed while treating patients with metastatic soft tissue sarcoma with pazopanib.

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.

scholarly journals A Phase II Nonrandomised Open-Label Study of Liposomal Daunorubicin (DaunoXome) in Advanced Soft Tissue Sarcoma

Sarcoma ◽  
2006 ◽  
Vol 2006 ◽  
pp. 1-5 ◽  
Author(s):  
Anne McTiernan ◽  
Jeremy Whelan ◽  
Michael Leahy ◽  
Penella J. Woll ◽  
Ian Judson
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Significant Activity ◽  
Open Label ◽  
Advanced Soft Tissue Sarcoma ◽  
Liposomal Daunorubicin ◽  
Open Label Study ◽  
Previously Treated ◽  
Grade 3 ◽  
Free Rate

Thirty four patients with advanced soft tissue sarcoma not previously treated with an anthracycline were treated with DaunoXome 100mg/m2 every 3 weeks. Thirty-three patients were evaluable for toxicity. Grade 3-4 neutropenia was seen in 20 patients (60.6%), complicated by febrile neutropenia in 2 (6.1%). Other grade 3 toxicities were rare. Among 32 patients assessable for response, one patient had a partial response, giving a response rate of 3.13% (95% confidence interval, 0.08–16.22%). Seven patients (21.9%) had stable disease, and 24 patients (75.0%) had disease progression. The median time to progression for all patients was 42 days (95% CI, 39–49) and the progression-free rate at 3 months was 12.5%. In conclusion, DaunoXome at this dose and schedule is well tolerated in patients with advanced soft tissue sarcoma, but is not associated with significant activity. Further studies at this dose and schedule cannot be recommended in this disease.

A randomized, double-blind, placebo (Pbo)-controlled phase III study of ombrabulin plus cisplatin in patients (pts) with advanced-stage soft-tissue sarcoma after failure of anthracycline and ifosfamide chemotherapies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 10506-10506
Author(s):  
Zsuzsanna Papai ◽  
Anthony W. Tolcher ◽  
Antoine Italiano ◽  
Didier Cupissol ◽  
Antonio Lopez-Pousa ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Phase Iii ◽  
Advanced Soft Tissue Sarcoma ◽  
Double Blind ◽  
Vascular Disrupting Agent ◽  
Phase Iii Study

10506 Background: Ombrabulin (AVE8062) is a vascular disrupting agent that damages established tumor vasculature and has demonstrated synergistic antitumor activity with cisplatin in vivo. In a phase I study, ombrabulin 25 mg/m² plus cisplatin 75 mg/m² was identified as the recommended dose in pts with solid tumors (AACR 2008; Abs 08-AB-4925). This phase III study evaluated the efficacy and safety of ombrabulin plus cisplatin in pts with advanced soft-tissue sarcoma (NCT00699517). Methods: Pts (aged ≥18 yrs, ECOG PS ≤2) with metastatic soft-tissue sarcoma who had received prior anthracycline and ifosfamide, with ≤2 prior chemotherapies for advanced disease, were randomized (1:1) to receive either ombrabulin 25 mg/m² or Pbo plus cisplatin 75 mg/m² every 3 weeks. The primary objective was to compare progression-free survival (PFS) between arms; secondary objectives included overall survival (OS) and safety. Results: Overall, 355 pts (median age 52 yrs; 51.5% male) were randomized (176 ombrabulin, 179 Pbo) in 44 centers worldwide. Median duration of follow-up was 27.9 and 30.5 months in Pbo and ombrabulin arms, respectively. PFS analysis showed a statistically significant improvement with ombrabulin (median 1.54 vs 1.41 months Pbo; HR=0.76, 95% CI 0.59–0.98; p=0.0302), with 3- and 6-month rates in favor of ombrabulin vs Pbo: 35.4% vs 24.9% and 19.3% vs 10.6%, respectively. A trend for an improvement with ombrabulin was observed in 3 of the 4 prespecified histology strata: liposarcoma, leiomyosarcoma, and “other”, but not for pleomorphic. Analysis of OS did not show statistically significant improvement with ombrabulin (median 11.43 vs 9.33 months Pbo, HR=0.85, 95% CI 0.67–1.09). OS rates at 1 year were in favor of ombrabulin (48.6% vs 42.4% Pbo). Grade 3/4 TEAEs more frequently seen with ombrabulin included neutropenia (19.2% vs 7.9% Pbo) and thrombocytopenia (8.5% vs 3.4% Pbo). Conclusions: Although this trial met its primary efficacy endpoint, the combination of ombrabulin and cisplatin did not demonstrate sufficient clinical benefit in pts with advanced soft-tissue sarcoma to warrant further study. Clinical trial information: NCT00699517.

scholarly journals Albumin-bound paclitaxel and gemcitabine combination therapy in soft tissue sarcoma

2020 ◽  
Author(s):  
Zhichao Tian ◽  
Fan Zhang ◽  
Po Li ◽  
Jiaqiang Wang ◽  
Jinpo Yang ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Malignant Tumors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Target Lesion ◽  
Free Survival ◽  
Metastatic Soft Tissue Sarcoma ◽  
Low Toxicity ◽  
Grade 3

Abstract Background: The evidence that albumin-bound paclitaxel (nab-paclitaxel) is safe and efficacious for the treatment of many types of malignant tumors is continuously increasing. However, the clinical data and evidence of nab-paclitaxel and gemcitabine in metastatic soft tissue sarcoma (STS) treatment are rare.Methods: The data of 17 patients with metastatic STS who received nab-paclitaxel/ gemcitabine chemotherapy between January 2019 and February 2020 were retrospectively reviewed. All patients were treated with nab-paclitaxel/ gemcitabine only after doxorubicin-based chemotherapy had failed. We evaluated the median progression-free survival (m-PFS), disease control rate (DCR), objective response rate (ORR) and adverse events (AEs) in these patients.Results: The m-PFS was 6 months (95% CI, 2–9 months), ORR was 41.2% and DCR was 70.6%. The average change in target lesion diameter from baseline was -19.06±45.74%. While the majority of the treatment patients experienced grade 1 or 2 AEs, grade 3 or 4 AEs were not common, but included neutropenia (17.6%), fatigue (11.8%), anemia (11.8%), leukopenia (11.8%), nausea (5.9%), peripheral neuropathy (5.9%), diarrhea (5.9%), and thrombocytopenia (5.9%). No treatment-related deaths occurred. Conclusion: Nab-paclitaxel/ gemcitabine combination chemotherapy is comparatively effective in the treatment of STS, demonstrates low toxicity, and is worthy of further study.

Topotecan/carboplatin regimen for refractory/recurrent rhabdomyosarcoma in children: Report from the AIEOP Soft Tissue Sarcoma Committee

2018 ◽  
Vol 105 (2) ◽  
pp. 138-143 ◽  
Author(s):  
Alessia Compostella ◽  
Maria Carmen Affinita ◽  
Michela Casanova ◽  
Giuseppe Maria Milano ◽  
Angela Scagnellato ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Tumor Response ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Late Relapse ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Grade 3 ◽  
Experienced Grade

Introduction: From 2002 to 2011, the Italian Soft Tissue Sarcoma Committee explored a combination of topotecan and carboplatin as a second-line strategy for children with resistant or relapsing rhabdomyosarcoma. Methods: Patients received two blocks of topotecan 2 mg/m2 on days 1, 2, and 3, and carboplatin 250 mg/m2 on days 4 and 5, followed by alternating blocks of topotecan–cyclophosphamide and carboplatin–etoposide for a total of six courses with 3-week intervals. Tumor response was assessed after two cycles, and local control was implemented when feasible. Results: A total of 38 patients were included in this study: 18/38 had alveolar rhabdomyosarcoma (RMS), 10/38 had metastatic disease at diagnosis, 8/38 had tumor progression during first-line chemotherapy, 21/38 had locoregional relapses, and 9/38 had distant relapses. Thirty-two patients could be assessed for tumor response to topotecan–carboplatin, and 9 (28%) showed a complete or partial response. Twenty-four patients experienced grade IV hematologic toxicity, while transient grade 1 tubulopathy, grade 3 mucositis, transient grade 2 nephrotoxicity, and a grade 2 decline in cardiac function occurred in one patient each. The 5-year overall and progression-free survival rates were 17% and 14%, respectively. Conclusion: the prognosis for children with resistant or relapsing RMS remains unsatisfactory. The topotecan–carboplatin regimen was well-tolerated. Though in case of late relapse the response rate was similar to those reported for other regimes, the result achieved remains unsatisfactory. New approaches, possibly including target agents, seem more attractive for future studies.

Phase III Trial of Two Investigational Schedules of Ifosfamide Compared With Standard-Dose Doxorubicin in Advanced or Metastatic Soft Tissue Sarcoma: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study

2007 ◽  
Vol 25 (21) ◽  
pp. 3144-3150 ◽  
Author(s):  
Paul Lorigan ◽  
Jaap Verweij ◽  
Zsuzsa Papai ◽  
Sjoerd Rodenhuis ◽  
Axel Le Cesne ◽  
...  
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Standard Dose ◽  
Single Agent ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Soft Tissue Sarcoma ◽  
Phase Iii Trial ◽  
Free Survival

Purpose Single-agent doxorubicin remains the standard treatment for advanced soft tissue sarcomas. Combining doxorubicin with standard-dose ifosfamide has not been shown to improve survival and is associated with a significantly increased toxicity; it is not known whether higher dose single-agent ifosfamide is superior to doxorubicin. Patients and Methods This randomized prospective multicenter phase III trial was designed to compare progression-free survival of patients with advanced soft tissue sarcoma receiving either regimen of standard doxorubicin 75 mg/m2 every 21 days, ifosfamide 9 g/m2 over 3 days continuous infusion, or ifosfamide 3 g/m2 per day in 3 hours over 3 days. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, and toxicity. Results The study included 326 patients. Grade 4 leukopenia, neutropenia, febrile neutropenia, and encephalopathy were more frequent in the ifosfamide arms. Progression-free survival, overall survival, and response rates were not significantly different between the three arms. An independent data monitoring committee reviewed the interim data and recommended early closure of the trial for futility (ie, no significant difference would be shown). Conclusion Single-agent doxorubicin remains the treatment of choice for patients with advanced soft tissue sarcoma.

Sign in / Sign up

Export Citation Format

Share Document