Time lapse analysis of tumor response in patients with soft tissue sarcoma treated with trabectedin: A pooled analysis of two phase II clinical trials

Takahashi, Shunji; Araki, Nobuhito; Sugiura, Hideshi; Ueda, Takafumi; Yonemoto, Tsukasa; Takahashi, Mitsuru; Morioka, Hideo; Hiraga, Hiroaki; Hiruma, Toru; Kunisada, Toshiyuki; Matsumine, Akihiko; Goda, Kazato; Kawai, Akira

doi:10.1002/cam4.2991

Cited by 8 publications

(7 citation statements)

References 14 publications

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“…A longer MFI could reflect a more indolent tumor biological behavior that could be related with a slower proliferation also in advanced disease. In line with that, the median time to response for trabectedin ranges from 3.7 to 5.3 in prospective phase II trials [20,21], which could indicate that indolent tumors are a favorable profile for trabectedin efficacy.…”

Section: Discussionsupporting

confidence: 64%

A Growth Modulation Index-Based GEISTRA Score as a New Prognostic Tool for Trabectedin Efficacy in Patients with Advanced Soft Tissue Sarcomas: A Spanish Group for Sarcoma Research (GEIS) Retrospective Study

Martínez‐Trufero

Sande-González

Luna

et al. 2021

Cancers

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The aim of this study was to identify an easily reliable prognostic score that selects the subset of advanced soft tissue sarcoma (ASTS) patients with a higher benefit with trabectedin in terms of time to progression and overall survival. A retrospective series of 357 patients with ASTS treated with trabectedin as second- or further-line in 19 centers across Spain was analyzed. First, it was confirmed that patients with high growth modulation index (GMI > 1.33) were associated with the better clinical outcome. Univariate and multivariate analyses were performed to identify factors associated with a GMI > 1.33. Thus, GEISTRA score was based on metastasis free-interval (MFI ≤ 9.7 months), Karnofsky < 80%, Non L-sarcomas and better response in the previous systemic line. The median GMI was 0.82 (0–69), with 198 patients (55%) with a GMI < 1, 41 (11.5%) with a GMI 1–1.33 and 118 (33.1%) with a GMI > 1.33. The lowest GEISTRA score showed a median of time-to-progression (TTP) and overall survival (OS) of 5.7 and 19.5 months, respectively, whereas it was 1.8 and 3.1 months for TTP and OS, respectively, for the GEISTRA 4 score. This prognostic tool can contribute to better selecting candidates for trabectedin treatment in ASTS.

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Section: Discussionsupporting

confidence: 64%

A Growth Modulation Index-Based GEISTRA Score as a New Prognostic Tool for Trabectedin Efficacy in Patients with Advanced Soft Tissue Sarcomas: A Spanish Group for Sarcoma Research (GEIS) Retrospective Study

Martínez‐Trufero

Sande-González

Luna

et al. 2021

Cancers

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“…The patients studied underwent a great deal of pretreatment; however, the last systematic treatment, surgery, and radiotherapy failed, and their condition progressed rapidly. Compared to doxorubicin, the risk of disease progression or death in high-risk groups taking trabectedin was statistically reduced by 45% (P<0.001) (30). The benefits of disease control can be observed regardless of a patient' disease histology or whether they had received previous systemic therapy.…”

Section: Discussionmentioning

confidence: 93%

Comparison between trabectedin and doxorubicin in soft-tissue sarcomas: a systematic review and meta-analysis

Dang¹,

Fu²,

Zhang³

et al. 2021

Ann Transl Med

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Background: This study sought to evaluate the differences between trabectedin and doxorubicin in the treatment of soft-tissue sarcoma (STS).Methods: Multiple databases, including PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure, were searched to retrieve relevant articles. Ultimately, the full text of 10 studies involving the use of trabectedin and doxorubicin in STS were reviewed. Review Manager 5.2 was used to evaluate the heterogeneity of the results of the selected articles. Forest plot, bias, and sensitivity analyses were carried out on the included articles.Results: Ten papers that met the criteria were included in this analysis. STS patients receiving trabectedin had longer progression-free survival than those receiving doxorubicin [overall mean difference (MD) =1.36, 95% confidence interval (CI): 1.04, 1.68, I 2 =6%, fixed-effects model]. The experimental group also had a longer overall survival period than the control group (MD =3.92, 95% CI: 0.23, 7.60, P=0.04 and I 2 =83%, random-effects model), and the experimental group had a better disease control rate than the control group (relative risk =1.2, P=0.03 and I 2 =45%, fixed-effects model). From the publication bias analysis and sensitivity analysis, we can guarantee the results are robust and unbiased.Discussion: Our research showed that STS patients who received trabectedin had better clinical effects and a longer survival time than those who received doxorubicin.

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“…Even if some patients with STS treated with trabectedin experience a tumor reduction after a few cycles, the median number of cycles reported to obtain an initial reduction in tumor size is higher. 13,14 In other words, trabectedin may need several months to provide its maximum dimensional response in MLP. Also, tumor response of MLP to trabectedin may follow a gastrointestinal stromal tumor-like pattern; there may be an initial tissue response, with a possible increase in size, followed by tumor shrinkage only at a later stage.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of Trabectedin and Radiotherapy for Patients With Myxoid Liposarcoma

Sanfilippo

Hindi²,

Jurado

et al. 2023

JAMA Oncol

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ImportancePreclinical data about the synergistic activity of radiotherapy (RT) and trabectedin have been reported. The combination of trabectedin and RT in treating myxoid liposarcomas appears worth exploring.ObjectiveTo explore the effectiveness and safety of trabectedin combined with RT.Design, Setting, and ParticipantsThis international, open-label, phase 2 nonrandomized clinical trial including 46 patients with myxoid liposarcoma was conducted in 4 centers in Spain, 1 in Italy, and 2 in France from July 1, 2016, to September 30, 2019. Eligible patients had to have a histologic, centrally reviewed diagnosis of localized resectable myxoid liposarcoma arising from an extremity or the trunk wall.InterventionsTrabectedin was administered at the recommended dose stemming from the phase 1 trial (1.5 mg/m2), with intravenous infusion during 24 hours every 21 days for a total of 3 cycles. Radiotherapy was started after completion of the first trabectedin infusion (cycle 1, day 2). Patients received 25 fractions of radiation for a total of 45 Gy. Surgery was planned 3 to 4 weeks after the administration of the last preoperative cycle and not until 4 weeks after the end of preoperative RT. Pathologic specimens were mapped in tumor sections to estimate the histologic changes and the percentage of viable tumor after neoadjuvant treatment.Main Outcomes and MeasuresThe primary objective of the phase 2 part of the study was overall response. Secondary objectives were effectiveness measured by relapse-free survival and activity measured by functional imaging and pathologic response.ResultsA total of 46 patients were enrolled. Four patients were not evaluable. The median age was 43 years (range, 18-77 years), and 31 patients were male (67%). Overall, 9 of 41 patients (22%) achieved a partial response with neoadjuvant treatment with trabectedin and RT, with 5 of 39 patients (13%) achieving a complete pathologic response and 20 of 39 patients (51%) having 10% or less of a viable remaining tumor. Partial responses according to Choi criteria were observed in 24 of 29 evaluable patients (83%), and no patient had disease progression. Treatment was well tolerated.Conclusions and RelevanceAlthough the primary end point of this phase 2 nonrandomized clinical trial was not met (Response Evaluation Criteria in Solid Tumors response in ≥70% of patients), results suggest this combination was well tolerated and effective in terms of pathologic response. Thus, trabectedin plus RT might be a treatment option regarding tolerability; further evidence should be generated in this setting.

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Time lapse analysis of tumor response in patients with soft tissue sarcoma treated with trabectedin: A pooled analysis of two phase II clinical trials

Cited by 8 publications

References 14 publications

A Growth Modulation Index-Based GEISTRA Score as a New Prognostic Tool for Trabectedin Efficacy in Patients with Advanced Soft Tissue Sarcomas: A Spanish Group for Sarcoma Research (GEIS) Retrospective Study

A Growth Modulation Index-Based GEISTRA Score as a New Prognostic Tool for Trabectedin Efficacy in Patients with Advanced Soft Tissue Sarcomas: A Spanish Group for Sarcoma Research (GEIS) Retrospective Study

Comparison between trabectedin and doxorubicin in soft-tissue sarcomas: a systematic review and meta-analysis

Effectiveness and Safety of Trabectedin and Radiotherapy for Patients With Myxoid Liposarcoma

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