scholarly journals Update on Systemic Therapy for Advanced Soft-Tissue Sarcoma

2020 ◽  
Vol 27 (11) ◽  
pp. 25-33 ◽  
Author(s):  
A. Smrke ◽  
Y. Wang ◽  
C. Simmons
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Systemic Therapy ◽  
English Language ◽  
Standard Of Care ◽  
Current Evidence ◽  
First Line ◽  
First Line Therapy

Background: Soft-tissue sarcoma (sts) represents a rare group of mesenchymal neoplasms comprising more than 50 heterogeneous subtypes. Great efforts have been made to increase the understanding of the treatment of advanced sts (unresectable or metastatic disease). We set out to determine whether outcomes for patients with advanced sts have improved over time and to assess the current evidence for systemic therapy. Methods: In a scoping review, we evaluated the contemporary evidence for systemic treatment of advanced sts in adults (>18 years of age). Phase i, ii, and iii studies of systemic therapy for advanced sts published in the English language were included. After abstract and full-text review of seventy-seven studies, sixty-two trials met the inclusion criteria. Results: The number of clinical trials conducted and published in advanced sts has increased over the last 30 years. Although median overall survival has increased, attempts at improving first-line therapy through dose intensification, doublet chemotherapy, or alternative backbones have not been successful. The optimal therapy beyond anthracyclines remains a challenge, especially given the heterogeneity that grouping multiple sts subtypes within clinical trials creates. However, increasing numbers of agents are being studied, and several studies had shown isolated benefit in progression-free or overall survival. Summary: First-line systemic therapy with an anthracycline remains the standard of care for advanced sts. However, choice of subsequent therapy beyond anthracyclines remains challenging. Novel systemic therapies, use of molecular diagnostics to direct therapy, subtype-specific trials, and learnings from real-world retrospective data are all important for improving outcomes in patients with advanced sts.

scholarly journals Update on Systemic Therapy for Advanced Soft Tissue Sarcoma

2020 ◽  
Vol 26 ◽  
Author(s):  
A. Smrke ◽  
Y. Wang ◽  
C. Simmons
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Systemic Therapy ◽  
English Language ◽  
Standard Of Care ◽  
Current Evidence ◽  
First Line ◽  
First Line Therapy ◽  
Full Text Review

Background: Soft tissue sarcoma (STS) is a rare group of mesenchymal neoplasms which contains over 50 heterogenous subtypes.  There have been great efforts to increase the understanding of treatment of advanced STS (unresectable or metastatic disease). We wished to determine if outcomes for patients with advanced STS have improved over time, and to assess the current evidence for systemic therapy. Methods: We performed a scoping review to evaluate the contemporary evidence for systemic treatment of advanced soft tissue in adults (>18 years old). Phase I, II, and III studies of systemic therapy for advanced STS published in the English language were included. After abstract and full text review of 77 studies, 62 trials met inclusion criteria.  Results: The number of clinical trials conducted and published in advanced STS has increased over the last 30 years. Although median OS has increased, attempts at improving first line therapy through dose intensification, doublet chemotherapy or alternative backbones have not been successful. The optimal therapy beyond anthracyclines remains a challenge, especially given the inherent heterogeneity of grouping multiple STS subtypes within clinical trials. However, increasing numbers of agents are being studied and several studies had shown isolated PFS or OS benefit.  Conclusions: First line anthracycline systemic therapy remains the standard of care for advanced STS.  However, choice of subsequent therapy beyond anthracyclines remains challenging. Novel systemic therapies, using molecular diagnostics to direct therapy, subtype specific trials and learning from real world retrospective data are all important in improving outcomes for patients with advanced STS.

Which goals should we pursue in each line of treatment for advanced soft tissue sarcoma?

2019 ◽  
Vol 15 (26s) ◽  
pp. 17-23
Author(s):  
Javier Martin-Broto ◽  
Nadia Hindi ◽  
David S Moura
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Disease Stage ◽  
Treatment Goals ◽  
Tumor Shrinkage ◽  
First Line ◽  
Advanced Soft Tissue Sarcoma ◽  
First Line Therapy ◽  
Line Therapy

Treatment goals for advanced soft tissue sarcoma (STS) vary according to disease stage and treatment line. In potentially resectable advanced disease, the goal of treatment is tumor shrinkage to facilitate surgical resection with better margins. Doxorubicin in combination with ifosfamide (or dacarbazine) is first-line therapy of choice in this setting. Tumor shrinkage is relevant not only for surgical rescue but also to obtain rapid symptomatic relief related to tumor volume. Doxorubicin monotherapy can be selected as first-line therapy in cases where disease control with less morbidity is the objective. Second-line therapy for metastatic disease generally aims for disease stabilization with good quality of life although, in some palliative or potentially resectable cases, tumor shrinkage may be relevant. To date, treatment aim has not been a critical factor in the design of clinical trials in advanced STS. In clinical practice, however, treatment is selected according to aim. Future clinical trials in patients with advanced STS should take treatment goals into account. Using illustrative case studies, evidence is examined which supports the current approach to treatment of advanced STS.

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 Overall Survival and Response to Systemic Therapy in Metastatic Extrauterine Leiomyosarcoma

Sarcoma ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
A. N. Shoushtari ◽  
J. Landa ◽  
D. Kuk ◽  
A. Sanchez ◽  
B. Lala ◽  
...  
Keyword(s):  
Overall Survival ◽  
Systemic Therapy ◽  
Objective Response ◽  
Soft Tissue Sarcomas ◽  
Older Age ◽  
First Line ◽  
Risk Of Death ◽  
First Line Therapy ◽  
Line Therapy ◽  
Male Sex

Background. Leiomyosarcomas (LMS) represent a heterogeneous subset of soft tissue sarcomas. Factors influencing prognosis for patients with metastatic extrauterine LMS (euLMS) are not well described. Limited data are available regarding responses to systemic therapy.Methods. We collected clinical and pathologic information for all patients with metastatic euLMS seen at Memorial Sloan Kettering Cancer Center between 1989 and 2012. Objective responses to first-line therapy were analyzed for a subset of patients with available baseline and on-treatment imaging using RECIST 1.1.Results. 215 patients with metastatic euLMS had a median overall survival (OS) of 2.6 years from the time of metastasis. Older age, male sex, and ≥3 initial sites of metastasis were associated with worse OS on multivariate analysis. Objective response rate (ORR) inN=113was 19% overall and 25%, 26%, and 25% for gemcitabine, gemcitabine plus docetaxel, and anthracycline-alkylator combinations. Patients whose tumors objectively responded to first-line therapy had a lower risk of death versus those who did not (Hazard Ratio 0.46; 95% CI: 0.26–0.79,p=0.005).Conclusions. Anthracycline- and gemcitabine-based regimens have similar activity in this cohort of euLMS. Prognostic factors for OS include older age, male sex, and ≥3 initial sites.

scholarly journals PML expression in soft tissue sarcoma: Prognostic and predictive value in alkylating agents/antracycline-based first line therapy

2012 ◽  
Vol 227 (4) ◽  
pp. 1657-1662 ◽  
Author(s):  
Bruno Vincenzi ◽  
Daniele Santini ◽  
Gaia Schiavon ◽  
Anna Maria Frezza ◽  
Marianna Silletta ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Predictive Value ◽  
Alkylating Agents ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals Doxorubicin/Adriamycin Monotherapy or Plus Ifosfamide in First-Line Treatment for Advanced Soft Tissue Sarcoma: A Pooled Analysis of Randomized Trials

2021 ◽  
Vol 11 ◽  
Author(s):  
Bi-Cheng Wang ◽  
Bo-Hua Kuang ◽  
Bo-Ya Xiao ◽  
Guo-He Lin
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Randomized Clinical Trials ◽  
Objective Response ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
First Line ◽  
Open Label ◽  
Advanced Soft Tissue Sarcoma

BackgroundDoxorubicin/Adriamycin (ADM) alone or combined with ifosfamide (IFO) (AI) is available for previously untreated advanced soft tissue sarcoma (ASTS). However, the clinical choice between them remains controversial. In this pooled analysis, we comprehensively compared the efficacy and tolerability of AI versus ADM in patients with ASTS.MethodsPubMed, Web of Science, EMBASE, and Cochrane Library were systematically searched from inception to April 14, 2021. Eligible studies were randomized clinical trials comparing AI to ADM. The primary outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Discontinuation rate (DR) and toxic death (TD) were explored as secondary outcomes.ResultsOverall, three open-label randomized phase 2/3 clinical trials with a total of 1108 newly diagnosed ASTS patients were enrolled. Between AI and ADM, pooled hazard ratios were 0.93 (95% confidence interval 0.58-1.50, p = 0.78) for OS and 0.85 (0.57-1.25, p = 0.41) for PFS. While pooled risk ratios for ORR, DR, and TD were 1.37 (0.94-1.99, p = 0.10), 1.04 (0.74-1.46, p = 0.82), and 0.68 (0.19-2.36, p = 0.54) respectively. No publication bias was observed across the studies.ConclusionIn the first-line setting, adding IFO to ADM failed to benefit ASTS patients against ADM alone, even with comparable tolerability.

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