Randomized Phase II Study of Azacitidine Alone or in Combination With Lenalidomide or With Vorinostat in Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia: North American Intergroup Study SWOG S1117
| العنوان: | Randomized Phase II Study of Azacitidine Alone or in Combination With Lenalidomide or With Vorinostat in Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia: North American Intergroup Study SWOG S1117 |
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| المؤلفون: | Rena Buckstein, Rakesh Gaur, Clara D. Bloomfield, Aziz Nazha, Richard Stone, Ehab Atallah, Megan Othus, Olatoyosi Odenike, Frederick R. Appelbaum, Alan F. List, Min Fang, Mario R. Velasco, Mikkael A. Sekeres, Elina K. Cook, Michael J. Rauh, Alyssa Cull, Mark R. Litzow, Diane Roulston, Eyal C. Attar, Anna Moseley, Yanming Zhang, Harry P. Erba, Steven D. Gore |
| المصدر: | Journal of Clinical Oncology. 35:2745-2753 |
| بيانات النشر: | American Society of Clinical Oncology (ASCO), 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, Oncology, Antimetabolites, Antineoplastic, Cancer Research, medicine.medical_specialty, Azacitidine, Chronic myelomonocytic leukemia, Phases of clinical research, Hydroxamic Acids, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Adverse effect, Lenalidomide, Vorinostat, Aged, Aged, 80 and over, business.industry, Myelodysplastic syndromes, Leukemia, Myelomonocytic, Chronic, Middle Aged, medicine.disease, Thalidomide, Myelodysplastic Syndromes, 030220 oncology & carcinogenesis, business, 030215 immunology, medicine.drug |
| الوصف: | Purpose Azacitidine is standard, first-line therapy in higher-risk myelodysplastic syndromes (MDS). Whether azacitidine-based combinations with lenalidomide or vorinostat produce superior overall response rates (ORRs) to azacitidine is not known. Patients and Methods North American Intergroup Study S1117 is a phase II/III trial that randomly assigned patients with higher-risk MDS and chronic myelomonocytic leukemia (CMML) 1:1:1 to azacitidine (75 mg/m2/day on days 1 to 7 of a 28-day cycle); azacitidine plus lenalidomide (10 mg/day on days 1 to 21); or azacitidine plus vorinostat (300 mg twice daily on days 3 to 9). The primary phase II end point was improved ORR. Results Of 277 patients from 90 centers, 92 received azacitidine, 93 received azacitidine plus lenalidomide, and 92 received azacitidine plus vorinostat. Median age was 70 years (range, 28 to 93 years), 85 patients (31%) were female, and 53 patients (19%) had CMML. Serious adverse events were similar across arms, although combination-arm patients were more likely to undergo nonprotocol-defined dose modifications ( P < .001).With a median follow-up of 23 months (range, 1 to 43 months), the ORR was 38% for patients receiving azacitidine, 49% for azacitidine plus lenalidomide ( P = .14 v azacitidine), and 27% for azacitidine plus vorinostat ( P = .16 v azacitidine). For patients with CMML, ORR was higher for azacitidine plus lenalidomide versus azacitidine (68% v 28%, P = .02) but similar for all arms across cytogenetic subgroups, as was remission duration and overall survival. ORR was higher with mutations in DNMT3A and lower for SRSF2, whereas ORR duration improved with fewer mutations. Lenalidomide dose reduction was associated with worse overall survival (hazard ratio, 1.30; P = .05). Conclusion Patients with higher-risk MDS treated with azacitidine-based combinations had similar ORR to azacitidine monotherapy, although patients with CMML benefitted from azacitidine plus lenalidomide. The efficacy of combination regimens may have been affected by dose modifications. |
| تدمد: | 1527-7755 0732-183X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::13ebf1f5cdfe456bf32a652b5c1f9663Test https://doi.org/10.1200/jco.2015.66.2510Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....13ebf1f5cdfe456bf32a652b5c1f9663 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15277755 0732183X |
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