Journal article
Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial.
- Prince HM Division of Cancer Medicine, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC, Australia; Epworth Healthcare, The University of Melbourne, Melbourne, VIC, Australia. Electronic address: Miles.Prince@petermac.org.
- Kim YH Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cancer Institute, Stanford, CA, USA.
- Horwitz SM Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
- Dummer R Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
- Scarisbrick J Department of Dermatology, University Hospital Birmingham, Birmingham, UK.
- Quaglino P Department of Medical Sciences, Dermatologic Clinic, University of Turin, Turin, Italy.
- Zinzani PL Institute of Haematology, University of Bologna, Bologna, Italy.
- Wolter P Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium.
- Sanches JA Department of Dermatology, University of São Paulo Medical School, São Paulo, Brazil.
- Ortiz-Romero PL Department of Dermatology, University Hospital 12 de Octubre, Institute i+12 Medical School, University Complutense, Madrid, Spain.
- Akilov OE Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA.
- Geskin L Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Dermatology, Columbia University, New York, NY, USA.
- Trotman J Department of Haematology, Concord Repatriation General Hospital, University of Sydney, Concord, NSW, Australia.
- Taylor K ICON Cancer Care, South Brisbane, QLD, Australia.
- Dalle S Department of Dermatology, Hospices Civils de Lyon, Claude Bernard Lyon 1 University, Lyon, France.
- Weichenthal M Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.
- Walewski J Maria Sklodowska-Curie Institute and Oncology Centre, Warsaw, Poland.
- Fisher D Dana-Farber Cancer Institute, Boston, MA, USA.
- Dréno B Faculty of Medicine, Nantes University, Nantes, France.
- Stadler R University Clinic for Dermatology, Johannes Wesling Medical Centre, Minden, Germany.
- Feldman T John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA.
- Kuzel TM Division of Hematology/Oncology/Cell Therapy, Department of Medicine, Rush University, Chicago, IL, USA.
- Wang Y Seattle Genetics Inc, Bothell, WA, USA.
- Palanca-Wessels MC Seattle Genetics Inc, Bothell, WA, USA.
- Zagadailov E Millennium Pharmaceuticals Inc, Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA.
- Trepicchio WL Millennium Pharmaceuticals Inc, Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA.
- Zhang W Millennium Pharmaceuticals Inc, Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA.
- Lin HM Millennium Pharmaceuticals Inc, Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA.
- Liu Y Millennium Pharmaceuticals Inc, Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA.
- Huebner D Millennium Pharmaceuticals Inc, Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA.
- Little M Millennium Pharmaceuticals Inc, Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA.
- Whittaker S St John's Institute of Dermatology, Guys and St Thomas NHS Foundation Trust, London, UK.
- Duvic M The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
- 2017-06-11
Published in:
- Lancet (London, England). - 2017
Antineoplastic Combined Chemotherapy Protocols
Brentuximab Vedotin
Humans
Immunoconjugates
Lymphoma, T-Cell, Cutaneous
Neoplasm Recurrence, Local
Quality of Life
English
BACKGROUND
Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas.
METHODS
In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5-50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499.
FINDINGS
Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4-26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1-58·4; p<0·0001). Grade 3-4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group.
INTERPRETATION
Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene.
FUNDING
Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc.
Cutaneous T-cell lymphomas are rare, generally incurable, and associated with reduced quality of life. Present systemic therapies rarely provide reliable and durable responses. We aimed to assess efficacy and safety of brentuximab vedotin versus conventional therapy for previously treated patients with CD30-positive cutaneous T-cell lymphomas.
METHODS
In this international, open-label, randomised, phase 3, multicentre trial, we enrolled adult patients with CD30-positive mycosis fungoides or primary cutaneous anaplastic large-cell lymphoma who had been previously treated. Patients were enrolled across 52 centres in 13 countries. Patients were randomly assigned (1:1) centrally by an interactive voice and web response system to receive intravenous brentuximab vedotin 1·8 mg/kg once every 3 weeks, for up to 16 3-week cycles, or physician's choice (oral methotrexate 5-50 mg once per week or oral bexarotene 300 mg/m2 once per day) for up to 48 weeks. The primary endpoint was the proportion of patients in the intention-to-treat population achieving an objective global response lasting at least 4 months per independent review facility. Safety analyses were done in all patients who received at least one dose of study drug. This trial was registered with ClinicalTrials.gov, number NCT01578499.
FINDINGS
Between Aug 13, 2012, and July 31, 2015, 131 patients were enrolled and randomly assigned to a group (66 to brentuximab vedotin and 65 to physician's choice), with 128 analysed in the intention-to-treat population (64 in each group). At a median follow-up of 22·9 months (95% CI 18·4-26·1), the proportion of patients achieving an objective global response lasting at least 4 months was 56·3% (36 of 64 patients) with brentuximab vedotin versus 12·5% (eight of 64) with physician's choice, resulting in a between-group difference of 43·8% (95% CI 29·1-58·4; p<0·0001). Grade 3-4 adverse events were reported in 27 (41%) of 66 patients in the brentuximab vedotin group and 29 (47%) of 62 patients in the physician's choice group. Peripheral neuropathy was seen in 44 (67%) of 66 patients in the brentuximab vedotin group (n=21 grade 2, n=6 grade 3) and four (6%) of 62 patients in the physician's choice group. One of the four on-treatment deaths was deemed by the investigator to be treatment-related in the brentuximab vedotin group; no on-treatment deaths were reported in the physician's choice group.
INTERPRETATION
Significant improvement in objective response lasting at least 4 months was seen with brentuximab vedotin versus physician's choice of methotrexate or bexarotene.
FUNDING
Millennium Pharmaceuticals Inc (a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd), Seattle Genetics Inc.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/S0140-6736(17)31266-7
- PMID 28600132
- Persistent URL
- https://sonar.ch/global/documents/258651
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