Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial
| Autor: | Carlos Besses, Alessandro M. Vannucchi, Fabrizio Pane, Vittorio Rosti, Simon Durrant, Francesco Passamonti, Igor Wolfgang Blau, Masayuki Hino, Carole B. Miller, Dany Habr, Mario Cazzola, Hui-Ling Zhen, Beatriz Moiraghi, Nathalie Francillard, Ruben A. Mesa, Srdan Verstovsek, Mark M. Jones, Jean-Jacques Kiladjian, Tamás Masszi, Pierre Zachee, Keita Kirito, Jingjin Li, Claire N. Harrison, Martin Griesshammer |
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| Přispěvatelé: | Verstovsek, Srdan, Vannucchi, Alessandro M., Griesshammer, Martin, Masszi, Tama, Durrant, Simon, Passamonti, Francesco, Harrison, Claire N., Pane, Fabrizio, Zachee, Pierre, Kirito, Keita, Besses, Carlo, Hino, Masayuki, Moiraghi, Beatriz, Miller, Carole B., Cazzola, Mario, Rosti, Vittorio, Blau, Igor, Mesa, Ruben, Jones, Mark M., Zhen, Huiling, Li, Jingjin, Francillard, Nathalie, Habr, Dany, Kiladjian, Jean Jacques |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male medicine.medical_specialty Ruxolitinib Phases of clinical research Hematocrit Gastroenterology 03 medical and health sciences 0302 clinical medicine Polycythemia vera Gene Frequency Internal medicine Nitriles Humans Medicine Combined Modality Therapy In patient Molecular Targeted Therapy Polycythemia Vera Protein Kinase Inhibitors Alleles Aged Janus Kinases Tumors -- Tractament Janus kinase 2 biology medicine.diagnostic_test business.industry Articles Hematology Middle Aged medicine.disease Surgery Clinical trial Pyrimidines Treatment Outcome 030220 oncology & carcinogenesis Mutation biology.protein Pyrazoles Female business Follow-Up Studies 030215 immunology medicine.drug |
| Popis: | RESPONSE is an open-label phase 3 study evaluating the Janus kinase 1/Janus kinase 2 inhibitor ruxolitinib versus best available therapy for efficacy/safety in hydroxyurea-resistant or intolerant patients with polycythemia vera. This preplanned analysis occurred when all patients completed the Week 80 visit or discontinued. Objectives included evaluating the durability of the primary response (Week 32 phlebotomy-independent hematocrit control plus ≥35% spleen volume reduction), its components, and that of complete hematologic remission; and long-term safety. Median exposure was 111 weeks; 91/110 (82.7%) patients randomized to ruxolitinib remained on treatment. No patients continued best available therapy (98/112 [87.5%] crossed over to ruxolitinib, most at/soon after Week 32). At Week 32, primary response was achieved by 22.7% vs. 0.9% of patients randomized to ruxolitinib and best available therapy, respectively (hematocrit control, 60.0% vs. 18.8%; spleen response, 40.0% vs. 0.9%). The probability of maintaining primary and hematocrit responses for ≥80 weeks was 92% and 89%, respectively; 43/44 spleen responses were maintained until Week 80. Complete hematologic remission at Week 32 was achieved in 23.6% of ruxolitinib-randomized patients; the probability of maintaining complete hematologic remission for ≥80 weeks was 69%. Among ruxolitinib crossover patients, 79.2% were not phlebotomized, and 18.8% achieved a ≥35% reduction from baseline in spleen volume after 32 weeks of treatment. New or worsening hematologic laboratory abnormalities in ruxolitinib-treated patients were primarily grade 1/2 decreases in hemoglobin, lymphocytes, and platelets. The thromboembolic event rate per 100 patient-years was 1.8 with randomized ruxolitinib treatment vs. 8.2 with best available therapy. These data support ruxolitinib as an effective long-term treatment option for hydroxyurea-resistant or intolerant patients with polycythemia vera. This trial was registered at clinicaltrials.gov identifier: 01243944. V received funding from and participated in advisory boards for Incyte Corporation. AMV served as a consultant for Novartis, participated in speakers bureaus for Novartis and Shire, and received research funding from Novartis. MG received travel reimbursements from Amgen, Roche, Novartis, and Shire. TM served as a consultant for Novartis and Janssen-Cilag. SD received honoraria and research funding from Novartis. CNH received honoraria from Sanofi, Novartis, and Baxter; served on speakers bureaus for Sanofi, Novartis, Shire, and Baxter; received research funding from Novartis; and received travel reimbursement from Novartis. KK received honoraria from Novartis. CB received honoraria from Novartis and Shire. FPan received honoraria from Novartis, Bristol-Myers Squibb, and Roche; served as a consultant for Bristol Myers Squibb and Ariad; received research funding from Novartis; and received travel reimbursements from Novartis and Roche. BM served on speakers bureaus for Novartis and Bristol-Myers Squibb. CBM received honoraria and served on a speakers bureau and as a consultant for Incyte Corporation. RM received honoraria and served as a consultant for Novartis and received research funding from Incyte Corporation, Gilead, CTI BioPharma, and Celgene. MMJ and HZ are employees and stockholders of Incyte Corporation. JL, NF, and DH are employees and stockholders of Novartis. J-JK served as a consultant for Novartis, Shire, and Incyte Corporation and received research funding from Novartis and AOP Orphan Pharmaceuticals. |
| Databáze: | OpenAIRE |
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