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Background: Recently, we performed a meta-analysis based on a literature review for STS trials (published 2003-2018, ≥10 adult patients) to update long-standing reference values for leiomyosarcomas. This work is extended for liposarcomas (LPS) and synovial sarcomas (SS)., Materials and Methods: Study endpoints were progression-free survival rates (PFSRs) at 3 and 6 months. Trial-specific estimates were pooled per treatment line (first-line or pre-treated) with random effects meta-analyses. The choice of the therapeutic benefit to target in future trials was guided by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS)., Results: Information was acquired for 1030 LPS patients (25 trials; 7 first-line, 17 pre-treated, 1 both) and 348 SS patients (13 trials; 3 first-line, 10 pre-treated). For LPS, the overall pooled first-line PFSRs were 69% (95%-CI 60-77%) and 56% (95%-CI 45-67%) at 3 and 6 months, respectively. These rates were 49% (95%-CI 40-57%)/28% (95%-CI 22-34%) for >1 lines. For SS, first-line PFSRs were 74% (95%-CI 58-86%)/56% (95%-CI 31-78%) at 3 and 6 months, and pre-treated rates were 45% (95%-CI 34-57%)/25% (95%-CI 16-36%). Following ESMO-MCBS guidelines, the minimum values to target are 79% and 69% for first-line LPS (82% and 69% for SS) at 3 and 6 months. For pre-treated LPS, recommended PFSRs at 3 and 6 months suggesting drug activity are 63% and 44% (60% and 41% for SS)., Conclusions: New benchmarks are proposed for advanced/metastatic LPS or SS to design future histology-specific phase II trials. More data are needed to provide definitive thresholds for the different LPS subtypes., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.-Y.B. has reported research support and honoraria from GSK Adaptimmune, Pharmamar, and Novartis; all outside the scope of this article. S.S. has reported personal financial interests (honoraria, consultancy, or advisory role) for Aadi, Bavarian Nordic, Bayer, Boeringher, Daiichi Sankyo, Deciphera, Epizyme, Glaxo, Ikena, Maxivax, Novartis, Pharmamar, Rainthera, and Servier; institutional financial interests with Advenchen, Amgen Dompè, Bayer, Daiichi Sankyo, Deciphera, Epizyme, Eli Lilly, Glaxo, Inhibrix, Hutchinson, Karyopharm, Novartis, Pfizer, Pharmamar, RainThera, and Springworks; all outside the scope of the submitted work. L.D'.A. has reported advisory board for PSI CRO Italy, GSK, AstraZenca, and Eisai; received travel support for meeting participation from Pharmamar, Eli Lilly, Celgene, and AstraZeneca; all outside the submitted article. W.G. has reported advisory role for Bayer, GSK, Springworks and PTC Therapeutics; received research grant support to the Institute from Eli Lilly; all outside the submitted work. All remaining authors have declared no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: In 2002, the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group reported well-established values for conducting phase II trials for soft-tissue sarcomas. An update is provided for leiomyosarcoma (LMS)., Materials and Methods: Clinical trials with advanced or metastatic LMS were identified via literature review in PubMed (published 2003-2018, ≥10 adult LMS patients). End-points were 3- and 6-month progression-free survival rates (PFSR-3m and PFSR-6m). When estimates could not be derived from publications, data requests were sent out. Treatments were classified as recommended (R-T) or non-recommended (NR-T) according to the ESMO 2018 guidelines. A random effects meta-analysis was used to pool trial-specific estimates for first-line (1L) or pre-treated (2L+) patients separately. The ESMO Magnitude of Clinical Benefit Scale was used to guide the treatment effect to target in future trials., Results: From 47 studies identified, we obtained information on 7 1L and 16 2L+ trials for 1500 LMS patients. Overall, in 1L, PFSR-3m and PFSR-6m were 74% (95% confidence interval [CI] 64-82%) and 58% (95% CI 50-66%), respectively. For 2L+, PFSR-3m was 48% (95% CI 41-54%), and PFSR-6m was 28% (95% CI 22-34%). No difference was observed between R-T and NR-T for first or later lines. Under the alternative that the true benefit amounts to a hazard ratio of 0.65, a PFSR-6m ≥70% can be considered to suggest drug activity in 1L. For 2L+, a PFSR-3m ≥62% or PFSR-6m ≥44% would suggest drug activity. Specific results are also provided for uterine LMS., Conclusions: This work provides a new benchmark for designing phase II studies for advanced or metastatic LMS., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: P.S. has reported honoraria from Deciphera, Blueprint Medicines, Boehringer Ingelheim; consultancy or advisory role for Deciphera, Ellipses Pharma, Blueprint Medicines, Transgene, Exelixis, Boehringer Ingelheim, Medscape, Guided Clarity, Ysios Capital; consultancy or advisory role to the Institution for Blueprint Medicines, Ellipses Pharma, Adaptimmune, Intellisphere, Transgene, Advanced Medical; has received support for travel, accommodation, expenses from Boehringer Ingelheim, MSD, Ipsen; research funding to the Institution from CoBioRes NV, Eisai, G1 Therapeutics, Novartis, PharmaMar; all outside the scope of the submitted work. S.S. has reported honoraria, consultancy or advisory role for Adaptimmune, Bayer, Daiichi-Sankyo, Deciphera, Epizyme, Eli Lilly, Glaxo, Immunedesign, Karyopharm, Maxivax, Novartis, PharmaMar; institutional financial interests with Advenchen, Amgen-Dompè, Bayer, Epizyme, Eli Lilly, Daiichi-Sankyo, Glaxo, Hutchinson MediPharma, Karyopharm, Novartis, Pfizer, PharmaMar, and Springworks; all outside the scope of this article. L.D’.A. has reported advisory boards for PSI, GSK, and Eisai; performed editorial activity for Novartis; received travel support from PharmaMar, Eli Lilly, and Celgene; all outside the submitted article. W.G. has reported advisory role for Bayer, GSK, and Springworks; received research grant support to the Institute from Eli Lilly and Novartis; all outside the submitted work. All remaining authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)