Overall Survival With Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, Phase III Trial.
| Title: | Overall Survival With Daratumumab, Bortezomib, and Dexamethasone in Previously Treated Multiple Myeloma (CASTOR): A Randomized, Open-Label, Phase III Trial. |
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| Authors: | Sonneveld P; Erasmus MC Cancer Institute, Rotterdam, the Netherlands.; Chanan-Khan A; Mayo Clinic Florida, Jacksonville, FL.; Weisel K; Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center of Hamburg-Eppendorf, Hamburg, Germany.; Nooka AK; Winship Cancer Institute, Emory University, Atlanta, GA.; Masszi T; Department of Internal Medicine and Haematology, Semmelweis University, Budapest, Hungary.; Beksac M; Ankara University, Ankara, Turkey.; Spicka I; 1st Department of Medicine - Department of Hematology, First Faculty of Medicine, Charles University and General Hospital in Prague, Prague, Czech Republic.; Hungria V; Clínica Médica São Germano, São Paulo, Brazil.; Munder M; Third Department of Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.; Mateos MV; University Hospital of Salamanca/IBSAL/Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain.; Mark TM; Department of Medicine, University of Colorado, Aurora, CO.; Levin MD; Albert Schweitzer Hospital, Dordrecht, the Netherlands.; Ahmadi T; Genmab US Inc, Plainsboro, NJ.; Qin X; Janssen Research & Development, LLC, Spring House, PA.; Garvin Mayo W; Janssen Research & Development, LLC, Raritan, NJ.; Gai X; Janssen Research & Development, LLC, Beijing, China.; Carey J; Janssen Research & Development, LLC, Spring House, PA.; Carson R; Janssen Research & Development, LLC, Spring House, PA.; Spencer A; Malignant Haematology and Stem Cell Transplantation Service, Alfred Health-Monash University, Melbourne, Australia. |
| Source: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2023 Mar 10; Vol. 41 (8), pp. 1600-1609. Date of Electronic Publication: 2022 Nov 22. |
| Publication Type: | Randomized Controlled Trial; Multicenter Study; Clinical Trial, Phase III; Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology; Original Publication: New York, N.Y. : Grune & Stratton, c1983- |
| MeSH Terms: | Multiple Myeloma*/drug therapy ; Neutropenia*; Bortezomib/adverse effects ; Dexamethasone/adverse effects ; Humans ; Aged ; Disease Progression ; Antibodies, Monoclonal |
| Abstract: | Purpose: At the primary analysis of CASTOR (median follow-up, 7.4 months), daratumumab plus bortezomib and dexamethasone (D-Vd) significantly prolonged progression-free survival versus bortezomib and dexamethasone (Vd) alone in relapsed or refractory multiple myeloma (RRMM). We report updated efficacy and safety results at the final analysis for overall survival (OS).; Methods: CASTOR was a multicenter, randomized, open-label, phase III study during which eligible patients with ≥ 1 line of prior therapy were randomly assigned to Vd (up to eight cycles) with or without daratumumab (until disease progression). After positive primary analysis and protocol amendment, patients receiving Vd were offered daratumumab monotherapy after disease progression.; Results: At a median (range) follow-up of 72.6 months (0.0-79.8), significant OS benefit was observed with D-Vd (hazard ratio, 0.74; 95% CI, 0.59 to 0.92; P = .0075). Median OS was 49.6 months with D-Vd versus 38.5 months with Vd. Prespecified subgroup analyses demonstrated an OS advantage with D-Vd versus Vd for most subgroups, including patients age ≥ 65 years and patients with one or two prior lines of therapy, International Staging System stage III disease, high-risk cytogenetic abnormalities, and prior bortezomib treatment. The most common (≥ 10%) grade 3/4 treatment-emergent adverse events with D-Vd versus Vd were thrombocytopenia (46.1% v 32.9%), anemia (16.0% v 16.0%), neutropenia (13.6% v 4.6%), lymphopenia (10.3% v 2.5%), and pneumonia (10.7% v 10.1%).; Conclusion: D-Vd significantly prolonged OS in patients with RRMM, with the greatest OS benefit observed in patients with one prior line of therapy. To our knowledge, our results, together with the OS benefit observed with daratumumab plus lenalidomide and dexamethasone in the phase III POLLUX study, demonstrate for the first time an OS benefit with daratumumab-containing regimens in RRMM (ClinicalTrials.gov identifier: NCT02136134 [CASTOR]). |
| Comments: | Comment in: J Clin Oncol. 2023 May 10;41(14):2668. doi: 10.1200/JCO.22.02850.. (PMID: 36940403); Comment in: J Clin Oncol. 2023 May 10;41(14):2667-2668. doi: 10.1200/JCO.22.02665.. (PMID: 36940404) |
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| Molecular Sequence: | ClinicalTrials.gov NCT02136134 |
| Substance Nomenclature: | 69G8BD63PP (Bortezomib); 7S5I7G3JQL (Dexamethasone); 4Z63YK6E0E (daratumumab); 0 (Antibodies, Monoclonal) |
| Entry Date(s): | Date Created: 20221122 Date Completed: 20230309 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10022857 |
| DOI: | 10.1200/JCO.21.02734 |
| PMID: | 36413710 |
| Database: | MEDLINE |
Randomized Controlled Trial; Multicenter Study; Clinical Trial, Phase III; Journal Article; Research Support, Non-U.S. Gov't