Systematic review of phase-I/II trials enrolling refractory and recurrent Ewing sarcoma: Actual knowledge and future directions to optimize the research

Autor: Sarah Dumont, Judith Landman-Parker, Marie-Cécile Le Deley, Nathalie Gaspar, Gilles Vassal, Maud Toulmonde, Arthur Felix, Pablo Berlanga
Rok vydání: 2020
Předmět:
0301 basic medicine
new cancer therapies
Cancer Research
medicine.medical_specialty
Databases
Factual
phase‐I/II trials
Antineoplastic Agents
Bone Neoplasms
Sarcoma
Ewing
Bone Sarcoma
03 medical and health sciences
0302 clinical medicine
Clinical Trials
Phase II as Topic
Refractory
Internal medicine
medicine
Recurrent Ewing Sarcoma
Clinical endpoint
Overall survival
Humans
Multicenter Studies as Topic
Radiology
Nuclear Medicine and imaging
Molecular Targeted Therapy
RC254-282
Response Evaluation Criteria in Solid Tumors
Randomized Controlled Trials as Topic
Original Research
Response rate (survey)
Clinical Trials
Phase I as Topic
business.industry
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Clinical Cancer Research
medicine.disease
Combined Modality Therapy
Progression-Free Survival
030104 developmental biology
Phase i ii
Treatment Outcome
Oncology
Research Design
030220 oncology & carcinogenesis
trial design
Sarcoma
Immunotherapy
Neoplasm Recurrence
Local
business
Ewing sarcoma
Zdroj: Cancer Medicine
Cancer Medicine, Vol 10, Iss 5, Pp 1589-1604 (2021)
ISSN: 2045-7634
Popis: 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 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. Conclusion This review supports the need to develop the international randomized phase‐II trials across all age ranges with PFS as primary endpoint.
Hundred and forty‐six phase‐II trials and 62 articles from 2005 to 2018 were analysed. Mostly multicentric, few trials were international (30%), only 5% were randomized. Results of 62 published trials enrolling 827 ES patients were disappointing. Combining chemotherapy with another agent is a promising strategy. International randomized trans‐age with PFS as primary endpoint could be promoted.
Databáze: OpenAIRE
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