TY - JOUR
T1 - New benchmarks to design clinical trials with advanced or metastatic liposarcoma or synovial sarcoma patients
T2 - An EORTC – Soft Tissue and Bone Sarcoma Group (STBSG) meta-analysis based on a literature review for soft-tissue sarcomas
AU - Kantidakis, Georgios
AU - Litière, Saskia
AU - Neven, Anouk
AU - Vinches, Marie
AU - Judson, Ian
AU - Blay, Jean Yves
AU - Wardelmann, Eva
AU - Stacchiotti, Silvia
AU - D'Ambrosio, Lorenzo
AU - Marréaud, Sandrine
AU - van der Graaf, Winette T.A.
AU - Kasper, Bernd
AU - Fiocco, Marta
AU - Gelderblom, Hans
N1 - Funding Information:
Georgios Kantidakis's work as a Fellow at EORTC Headquarters was supported by a grant from the EORTC Soft Tissue and Bone Sarcoma Group and Leiden University Medical Center department of Medical Oncology as well as from the EORTC Cancer Research Fund (ECRF). Marie Vinches's work as a Fellow at EORTC Headquarters was supported by a grant from Fonds Cancer (FOCA) from Belgium. This publication was supported by a donation from Kom Op Tegen Kanker (Stand up to Cancer), the Flemish Cancer Society from Belgium. The authors would like to express their appreciation to all the primary investigators (PI) who shared valuable PFS estimates at 3 and 6 months for liposarcoma (LPS) and/or synovial sarcoma (SS) patients, namely, Dr Akira Kawai (1 study; LPS), Dr PA Cassier (1 study; LPS), Dr Mark A. Dickson (2 studies; LPS), Dr Joan Maurel (1 study; LPS), Dr Beatrice Seddon (1 study; LPS), Dr. Paul F. Robbins (1 study; SS), and Prof Antoine Italiano (1 study; LPS). In addition, we would like to sincerely thank the following sponsors SARC (4 studies: PI Prof Scott M. Schuetze; LPS, PI Prof Rashmi Chugh; LPS and SS, PI Prof Hussein A Tawbi; LPS and SS, PI Dr William D Tap; LPS and SS), PharmaMar (2 studies: PI Prof Nicolas Penel; LPS and SS, PI Prof Jean-Yves Blay; LPS and SS), Eisai (1 study: PI Prof Patrick Schöffski; LPS), and Taiho Pharmaceutical (1 study: PI Dr Akira Kawai; LPS) for the provision of summary PFS estimates at 3 and 6 months. All analyses and conclusions in this article are the sole responsibility of the authors and do not necessarily reflect the opinions or views of these primary investigators, SARC, PharmaMar, Eisai, or Taiho Pharmaceutical.
Funding Information:
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.
Funding Information:
This work was supported by the European Organisation for Research and Treatment of Cancer - Soft Tissue and Bone Sarcoma Group (EORTC-STBSG). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - Advanced or metastatic population
KW - Efficacy
KW - Liposarcoma
KW - Meta-analysis
KW - Study design
KW - Synovial sarcoma
UR - http://www.scopus.com/inward/record.url?scp=85138100622&partnerID=8YFLogxK
UR - https://pubmed.ncbi.nlm.nih.gov/36116829
U2 - 10.1016/j.ejca.2022.07.010
DO - 10.1016/j.ejca.2022.07.010
M3 - Review article
C2 - 36116829
SN - 0959-8049
VL - 174
SP - 261
EP - 276
JO - European Journal of Cancer
JF - European Journal of Cancer
ER -