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Systematic review of phase-I/II trials enrolling refractory and recurrent Ewing sarcoma: Actual knowledge and future directions to optimize the research.
- Source :
-
Cancer medicine [Cancer Med] 2021 Mar; Vol. 10 (5), pp. 1589-1604. Date of Electronic Publication: 2021 Jan 15. - Publication Year :
- 2021
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Abstract
- Background: Optimal Phase-II design to evaluate new therapies in refractory/relapsed Ewing sarcomas (ES) remains imperfectly defined.<br />Objectives: Recurrent/refractory ES phase-I/II trials analysis to improve trials design.<br />Methods: Comprehensive review of therapeutic trials registered on five databases (who.int/trialsearch, clinicaltrials.gov, clinicaltrialsregister.eu, e-cancer.fr, and umin.ac.jp) and/or published in PubMed/ASCO/ESMO websites, between 2005 and 2018, using the criterion: (Ewing sarcoma OR bone sarcoma OR sarcoma) AND (Phase-I or Phase-II).<br />Results: The 146 trials identified (77 phase-I/II, 67 phase-II, and 2 phase-II/III) tested targeted (34%), chemo- (23%), immune therapies (19%), or combined therapies (24%). Twenty-three trials were ES specific and 48 had a specific ES stratum. Usually multicentric (88%), few trials were international (30%). Inclusion criteria cover the recurrent ES age range for only 12% of trials and allowed only accrual of measurable diseases (RECIST criteria). Single-arm design was the most frequent (88%) testing mainly single drugs (61%), only 5% were randomized. Primary efficacy outcome was response rate (RR=CR+PR; Complete+Partial response) (n = 116/146; 79%), rarely progression-free or overall survival (16% PFS and 3% OS). H0 and H1 hypotheses were variable (3%-25% and 20%-50%, respectively). The 62 published trials enrolled 827 ES patients. RR was poor (10%; 15 CR=1.7%, 68 PR=8.3%). Stable disease was the best response for 186 patients (25%). Median PFS/OS was of 1.9 (range 1.3-14.7) and 7.6 months (5-30), respectively. Eleven (18%) published trials were considered positive, with median RR/PFS/OS of 15% (7%-30%), 4.5 (1.3-10), and 16.6 months (6.9-30), respectively.<br />Conclusion: This review supports the need to develop the international randomized phase-II trials across all age ranges with PFS as primary endpoint.<br /> (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
- Subjects :
- Antineoplastic Agents therapeutic use
Clinical Trials, Phase I as Topic statistics & numerical data
Clinical Trials, Phase II as Topic statistics & numerical data
Combined Modality Therapy statistics & numerical data
Databases, Factual statistics & numerical data
Humans
Immunotherapy statistics & numerical data
Molecular Targeted Therapy statistics & numerical data
Multicenter Studies as Topic statistics & numerical data
Progression-Free Survival
Randomized Controlled Trials as Topic statistics & numerical data
Response Evaluation Criteria in Solid Tumors
Treatment Outcome
Bone Neoplasms therapy
Clinical Trials, Phase I as Topic standards
Clinical Trials, Phase II as Topic standards
Neoplasm Recurrence, Local therapy
Research Design standards
Sarcoma, Ewing therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2045-7634
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cancer medicine
- Publication Type :
- Academic Journal
- Accession number :
- 33452711
- Full Text :
- https://doi.org/10.1002/cam4.3712