Systematic review of phase-I/II trials enrolling refractory and recurrent Ewing sarcoma: Actual knowledge and future directions to optimize the research
Abstract
Background: Optimal Phase-II design to evaluate new therapies in refractory/relapsed Ewing sarcomas (ES) remains imperfectly defined.
Objectives: Recurrent/refractory ES phase-I/II trials analysis to improve trials design.
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).
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…
How strong is the evidence?
Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 827 participants or records.
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