Efficacy and safety of pharmacological interventions in second- or later-line treatment of patients with advanced soft tissue sarcoma: a systematic review

Abstract

BackgroundCurrent guidelines recommend anthracycline-based chemotherapy primarily with doxorubicin either as monotherapy or in combination with ifosfamide as the first-line treatment for most advanced STS subtypes. Therapeutic options after failure of doxorubicin and/or ifosfamide are limited. This study aimed to comprehensively review available data on the activity and safety of interventions in second- or later-line treatment of advanced STS.MethodsElectronic literature databases (Embase®, MEDLINE®, MEDLINE® In-Process, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) were searched from 1980 to 01 March 2012 to identify randomised controlled trials (RCTs) and non-randomised studies (both prospective and retrospective) evaluating pharmacological interventions in patients with advanced STS pre-treated with anthracycline- and/or ifosfamide-based therapy.ResultsThe review identified six RCTs (one phase III and five phase II trials) and 94 non-randomised studies. Based on the primary trial endpoints, RCTs demonstrated favourable efficacy for pazopanib over placebo (PFS: 4.6 months vs. 1.6 months), gemcitabine plus dacarbazine over dacarbazine monotherapy (3-month PFS rate: 54.2% vs. 35.2%), and trabectedin 3-weekly schedule over weekly schedule (TTP: 3.7 months vs. 2.3 months. The non-randomised studies demonstrated heterogeneity in efficacy and safety results.ConclusionsAcross the RCTs, pazopanib over placebo, gemcitabine-dacarbazine over dacarbazine, and trabectedin 3-weekly over weekly regimen clearly demonstrated a PFS advantage in the second- and later-line treatment of advanced STS. With only one phase III trial in this setting, there is a clear need for additional comparative trials to better understand the risk: benefit ratios of available agents and combinations.

Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial

“…Soft tissue sarcoma is a rare and diverse group of solid tumours originating from mesenchymal precursors 1,2 . They account for approximately 1% of all new adult malignancies.…”

“…They account for approximately 1% of all new adult malignancies. 2,3 Doxorubicin, either alone or in combination, remains a standard of care. However, survival for treated patients with metastatic disease is only 12 to 16 months, and the two-year survival rate is approximately 30%.…”

Cost-Effectiveness of Pazopanib in Advanced Soft-Tissue Sarcoma in Canada

“…First, it focused on a comparison of pazopanib with placebo only and did not consider other systemic therapies such as gemcitabine with or without docetaxel and ifosfamide that are frequently used as second-line therapy in Canada 18 . Because controlled clinical trials comparing the efficacy of pazopanib or placebo with those treatments are unavailable 17 , it was infeasible to perform a robust comparison of the cost-effectiveness of pazopanib against those active therapies. In the economic evaluation submitted to the pan-Canadian Oncology Drug Review that was based on the model reported here and on an unadjusted ("naïve") indirect comparison, pazopanib was found to dominate (that is, be less costly and yield more qalys than) gemcitabine monotherapy and gemcitabine plus docetaxel.…”

“…Although patients with asts can, in clinical practice in Canada, receive a variety of systemic therapies after anthracycline-based chemotherapy 10,18,19 (most notably ifosfamide or gemcitabine with or without docetaxel), no randomized controlled trials have compared pazopanib or placebo with such therapies 17 , and a robust comparison of pazopanib with those agents was therefore infeasible.…”

Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement

“…If the recurrence is in the pelvis outside of the vagina, confirmed through surgery, pelvic RT is recommended. If recurrence is confirmed to be outside of the pelvis, chemotherapy is recommended, and in patients with ESS, hormonal therapy can be recommended [103104105]. …”