Olaratumab in the management of advanced soft tissue sarcoma

2018 ◽  
Vol 25 (2) ◽  
pp. 442-448 ◽  
Author(s):  
Chrystia M Zobniw ◽  
Van Anh Trinh ◽  
Kristi Posey ◽  
Neeta Somaiah
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Survival Data ◽  
Pediatric Population ◽  
Advanced Soft Tissue Sarcoma ◽  
Phase 3 ◽  
Management Algorithm ◽  
Active Research ◽  
Confirmatory Phase

Olaratumab, the first-in-class anti-PDGFRα monoclonal antibody, has been contingently approved in combination with doxorubicin to treat adult patients with advanced soft tissue sarcoma for improving progression-free and overall survival. Olaratumab–doxorubicin combination has tolerable safety profile, which mimics that of doxorubicin monotherapy, with the exception of infusion-related reactions. Survival data of an ongoing confirmatory phase 3 trial are forthcoming to ascertain the optimal role of this product in the management algorithm of advanced soft tissue sarcoma. Active research is ongoing to identify biomarkers predictive of clinical benefit to olaratumab, to expand its utility to the pediatric population, and to explore its safety and efficacy in combination with other active regimens.

Prognostic role of HMG proteins in a series of 301 advanced soft tissue sarcoma patients: A Spanish Group for Sarcoma Research Study (GEIS).

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 11573-11573 ◽  
Author(s):  
Nadia Hindi ◽  
Rafael Ramos ◽  
Javier Martinez-Trufero ◽  
Rosa Maria Alvarez Alvarez ◽  
Magda Cordeiro ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Research Study ◽  
Hmg Proteins ◽  
Prognostic Role ◽  
Advanced Soft Tissue Sarcoma

scholarly journals Sequential Dose-Dense Doxorubicin and Ifosfamide in Advanced Soft-Tissue Sarcoma Patients in an Out-Patient-Basis Schedule

Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-7
Author(s):  
G. F. G. Almeida ◽  
G. Castro ◽  
I. M. L. Snitcovsky ◽  
S. A. Siqueira ◽  
E. H. Akaishi ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
High Frequency ◽  
Locally Advanced ◽  
Front Line ◽  
Advanced Soft Tissue Sarcoma ◽  
Grade 3 ◽  
Dose Dense ◽  
Sequential Strategy

Aims. This phase II study explored activity/safety of front-line dose-dense chemotherapy in high-grade STS (soft tissue sarcoma) patients and tested ezrin as prognostic factor.Patients and Methods. The protocol consisted of three cycles of doxorubicin (DOXO) 30 mg/m2on days 1–3 every 2 weeks, followed by three cycles of ifosfamide (IFO) 2.5 g/m2two hours a day on days 1–5 every 3 weeks, with GCSF support. Ezrin was assessed immunohistochemically.Results. Twenty patients, 13 metastatic and 7 locally advanced, were enrolled. Median age was 39 years (25–60). Median dose intensities were 42 mg/m2/week and 3.6 g/m2/week for DOXO and IFO, respectively. Grade 3/4 toxicities occurred in 18 patients. Response rate was 15% (3 of 20) by RECIST. Patients younger than 45 years with locally advanced disease and synovial histology presented longer survival. A trend towards longer survival was observed among ezrin-positive patients.Conclusions. This dose-dense schedule should not be routinely used due to its high frequency of toxic events; however, a sequential strategy with DOXO and IFO may benefit selected patients and should be further explored with lower doses. The role of ezrin as a prognostic marker should be confirmed in a larger group of patients.

scholarly journals Symptom Burden, Survival and Palliative Care in Advanced Soft Tissue Sarcoma

Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Nicholas J. Gough ◽  
Clare Smith ◽  
Joy R. Ross ◽  
Julia Riley ◽  
Ian Judson
Keyword(s):  
Palliative Care ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Locally Advanced ◽  
Symptom Burden ◽  
Median Number ◽  
Best Supportive Care ◽  
Advanced Soft Tissue Sarcoma ◽  
Significant Symptom

Introduction. The symptom burden and role of palliative care (PC) in patients with advanced soft tissue sarcoma (STS) are not well defined.Methods. This study retrospectively reviewed both symptoms and PC involvement in patients known to an STS referral centre who died in one calendar year.Results. 81 patients met inclusion criteria of which 27% had locally advanced disease and 73% metastases at initial referral. The median number of symptoms was slowly progressive ranging from 2 (range 0–5) before first-line chemotherapy () to 3 (range 1–6) at the time of best supportive care (BSC) decision (). Pain and dyspnoea were the commonest symptoms. Median overall survival from BSC decision was 3.4 weeks. 88% had PC involvement (either hospital, community, or both) with median time from first PC referral to death of 16 (range 0–110) weeks.Conclusions. Patients with metastatic STS have a significant symptom burden which justifies early PC referral. Pain, including neuropathic pain, is a significant problem. Dyspnoea is common, progressive and appears to be undertreated. Time from BSC decision to death is short, and prospective studies are required to determine whether this is due to overtreatment or very rapid terminal disease progression.

scholarly journals Advances in soft-tissue sarcoma – There are no mistakes, only lessons to learn!

2019 ◽  
Vol 08 (04) ◽  
pp. 258-259
Author(s):  
Sameer Rastogi ◽  
Parisa Manasa ◽  
Aditi Aggarwal ◽  
Kaushal Kalra
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Poor Correlation ◽  
Phase 2 ◽  
Advanced Soft Tissue Sarcoma ◽  
Homogeneous Population ◽  
Undifferentiated Sarcoma ◽  
Phase 2 Trial ◽  
Well Differentiated

Abstract Background: In this decade the treatment of advanced sarcoma has seen many highs and lows in terms of successful trials and failed trials. This is possible due to great collaborations, newer therapies and histology focused trials. Methods: In ASCO 2019 many sarcoma trials were presented and we chose 3 challenging clinical trials that widen our perspective on soft tissue sarcoma. We have critically analyzed the data and have discussed the implications of these trials on current practice. First trial was ANNOUNCE trial which was done to confirm the efficacy of olaratumab after its dramatic success in advanced soft tissue sarcoma in a phase 2 trial. Another trial STRASS trial, which was unique because of being first successfully conducted randomized trial addressing preoperative radiotherapy in retroperitoneal soft tissue sarcoma. Third trial was phase 2 trial SARC 028 trial exploring the role of immunotherapy in pleomorphic undifferentiated sarcoma and liposarcoma subgroup. Result: ANNOUNCE trial failed to show OS benefit in olaratumab/doxorubicin arm as compared to doxorubicin/placebo arm . Based upon this FDA has revoked the approval of olaratumab leading to nihilism and disappointment amongst oncologists. In STRASS trial failed to meet the primary end point though there was a benefit in the liposarcoma subgroup in terms of abdominal recurrence free survival. There are several reasons that this trial might have failed. First, RPSs are not homogeneous population. RPSs might behave very differently as per the histopathology ranging from well differentiated LPS to leiomyosarcoma. Since the event rate in well-differentiated liposarcoma might happen late, the median follow-up of 43 months might not be sufficient. In SARC trial ORR in pleomorphic undifferentiated sarcoma (PUS) cohort was 9/40 (22.5%), while response rates in liposarcoma cohort were 4/39 (10.2%). There was poor correlation between the response and the tumor cells’ PD-L1 positivity. Simultaneously, we must not take for granted the role of pembrolizumab in PUS as the previous study (PEMBROSARC) had also showed dismal outcomes with immunotherapy. Conclusion: In this paper we discuss the intricacies of these trials and how they affect the rapidly changing landscape in advanced soft tissue sarcoma.

Soft Tissue Sarcoma: The Important Role of Initial MRI Reports for Disease Control

2020 ◽  
Author(s):  
S Weiß ◽  
A Korthaus ◽  
K-H Frosch ◽  
C Schlickewei ◽  
M Priemel
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Disease Control
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