Abstract
Purpose
Soft tissue sarcomas (STS) are diagnosed in 4–6 cases per 100 000 people a year and are associated with an unfavorable prognosis. Around one-third of patients will develop metastatic disease that requires palliative systemic therapy. Current therapeutic options have limited activity, and new treatments are tested, mainly in phase II trials. There is high variability and no standardization of phase II designs. We aimed to analyze the current landscape of phase II studies in STS and evaluate how its statistical design can affect the results.
Methods
Full-text phase II studies published in STS patients between 2005 and 2020 were identified and analyzed.
Results
We have identified 102 trials, of which 77.4% were single-arm trials, 16.7% were randomized comparative trials (RCT), and 5.9% were randomized noncomparative trials. Including multiple cohorts, 22 randomized and 128 single-arm cohorts were analyzed. Nearly 80% of trials reported full statistical bases of the design. Over 20 different primary endpoints were used, with PFS as the most common in RCT trials (81.8%) and ORR (36.7%) and 3-months progression-free survival (PFS) rate (21.9%) in single-arm trials. Overall, 27.3% of RCT and 37.5% of single-arm trials were positive. Among single-arm trials, studies using 3- or 6-month rates were more often positive than those based on ORR.
Conclusions
There is high heterogeneity in sarcoma trial designs, mainly in primary-endpoint and hypotheses used for size calculation. There is an unmet need for standardization that will incorporate factors associated with the rarity of the disease, outcomes detected in previous trials and real-life studies, and specific characteristics of new therapeutic agents.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
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Main study conception was created by Pawel Sobczuk. All authors contributed to the study conception and design. Material preparation and data collection and analysis were performed by Hubert Batruk, Paulina Wojcik, Krzystzof Iwaniak and Pawel Sobczuk. Data analyses was performed by Pawel Sobczuk, Katarzyna Kozak and Piotr Rutkowski. The first draft of the manuscript was written by Pawel Sobczuk and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Work was supersized by Piotr Rutkowski.
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P.S. has received travel grants from MSD, Roche, Novartis, and Pierre Fabre and honoraria for lectures from Swixx BioPharma and BMS. Non-financial interests: European Society of Medical Oncology—Officer; Polish Society of Clinical Oncology—Member of Board of Directors. K.K. has received honoraria for lectures from BMS, MSD, Novartis, Pfizer, and Pierre Fabre. S.K. has received travel grants from Pierre Fabre. P.R. (Piotr Rutkowski): Personal financial interests: Blueprint Medicines, Advisory Board; BMS, invited speaker, honoraria for lectures, Advisory Board; Merck, Advisory Board; Merck, invited speaker, honoraria for lectures; MSD, Advisory Board; Novartis, invited speaker; Pierre Fabre, invited speaker, honoraria for lectures; Pierre Fabre, Advisory Board; Sanofi, Advisory Board, invited speaker. Institutional interests: BMS, funding, financial interest, research grant for institution; Pfizer, research grant, financial interest, research grant for ISS. Non-financial interests: ASCO, Officer; Polish Society of Surgical Oncology, Member of Board of Directors. H.B., P.W. and K.I. declare no conflict of interest.
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Sobczuk, P., Bątruk, H., Wójcik, P. et al. In search of effective therapies: the current landscape of phase II trials in patients with advanced soft tissue sarcoma. J Cancer Res Clin Oncol 149, 2771–2782 (2023). https://doi.org/10.1007/s00432-022-04149-0
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DOI: https://doi.org/10.1007/s00432-022-04149-0