A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)

R. Hájek, T. Masszi, M. T. Petrucci, A. Palumbo, L. Rosiñol, A. Nagler, K. L. Yong, A. Oriol, J. Minarik, L. Pour, M. A. Dimopoulos, V. Maisnar, D. Rossi, H. Kasparu, J. van Droogenbroeck, D. B. Yehuda, I. Hardan, M. Jenner, M. Calbecka, M. DávidJ. de la Rubia, J. Drach, Z. Gasztonyi, S. Górnik, X. Leleu, M. Munder, M. Offidani, N. Zojer, K. Rajangam, Y. L. Chang, J. F. San-Miguel, H. Ludwig

Research output: Article

56 Citations (Scopus)

Abstract

This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m2 on days 1 and 2 of cycle 1; 27 mg/m2 thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4–14.4) vs 10.0 months (95% CI 7.7–12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760–1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients.Leukemia advance online publication, 15 July 2016; doi:10.1038/leu.2016.176.

Original languageEnglish
JournalLeukemia
DOIs
Publication statusAccepted/In press - júl. 15 2016

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Multiple Myeloma
Cyclophosphamide
Adrenal Cortex Hormones
Confidence Intervals
Survival
Safety Management
carfilzomib
Neutropenia
Intravenous Infusions
Thrombocytopenia
Dexamethasone
Multicenter Studies
Disease-Free Survival
Publications
Anemia
Leukemia
Control Groups

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

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A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). / Hájek, R.; Masszi, T.; Petrucci, M. T.; Palumbo, A.; Rosiñol, L.; Nagler, A.; Yong, K. L.; Oriol, A.; Minarik, J.; Pour, L.; Dimopoulos, M. A.; Maisnar, V.; Rossi, D.; Kasparu, H.; van Droogenbroeck, J.; Yehuda, D. B.; Hardan, I.; Jenner, M.; Calbecka, M.; Dávid, M.; de la Rubia, J.; Drach, J.; Gasztonyi, Z.; Górnik, S.; Leleu, X.; Munder, M.; Offidani, M.; Zojer, N.; Rajangam, K.; Chang, Y. L.; San-Miguel, J. F.; Ludwig, H.

In: Leukemia, 15.07.2016.

Research output: Article

Hájek, R, Masszi, T, Petrucci, MT, Palumbo, A, Rosiñol, L, Nagler, A, Yong, KL, Oriol, A, Minarik, J, Pour, L, Dimopoulos, MA, Maisnar, V, Rossi, D, Kasparu, H, van Droogenbroeck, J, Yehuda, DB, Hardan, I, Jenner, M, Calbecka, M, Dávid, M, de la Rubia, J, Drach, J, Gasztonyi, Z, Górnik, S, Leleu, X, Munder, M, Offidani, M, Zojer, N, Rajangam, K, Chang, YL, San-Miguel, JF & Ludwig, H 2016, 'A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)', Leukemia. https://doi.org/10.1038/leu.2016.176
Hájek, R. ; Masszi, T. ; Petrucci, M. T. ; Palumbo, A. ; Rosiñol, L. ; Nagler, A. ; Yong, K. L. ; Oriol, A. ; Minarik, J. ; Pour, L. ; Dimopoulos, M. A. ; Maisnar, V. ; Rossi, D. ; Kasparu, H. ; van Droogenbroeck, J. ; Yehuda, D. B. ; Hardan, I. ; Jenner, M. ; Calbecka, M. ; Dávid, M. ; de la Rubia, J. ; Drach, J. ; Gasztonyi, Z. ; Górnik, S. ; Leleu, X. ; Munder, M. ; Offidani, M. ; Zojer, N. ; Rajangam, K. ; Chang, Y. L. ; San-Miguel, J. F. ; Ludwig, H. / A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS). In: Leukemia. 2016.
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abstract = "This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m2 on days 1 and 2 of cycle 1; 27 mg/m2 thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95{\%} of patients received cyclophosphamide. Median OS was 10.2 (95{\%} confidence interval (CI) 8.4–14.4) vs 10.0 months (95{\%} CI 7.7–12.0) with carfilzomib vs control (hazard ratio=0.975; 95{\%} CI 0.760–1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4{\%}). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7{\%}), thrombocytopenia (24.2 vs 22.2{\%}) and neutropenia (7.6 vs 12.4{\%}) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients.Leukemia advance online publication, 15 July 2016; doi:10.1038/leu.2016.176.",
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T1 - A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS)

AU - Hájek, R.

AU - Masszi, T.

AU - Petrucci, M. T.

AU - Palumbo, A.

AU - Rosiñol, L.

AU - Nagler, A.

AU - Yong, K. L.

AU - Oriol, A.

AU - Minarik, J.

AU - Pour, L.

AU - Dimopoulos, M. A.

AU - Maisnar, V.

AU - Rossi, D.

AU - Kasparu, H.

AU - van Droogenbroeck, J.

AU - Yehuda, D. B.

AU - Hardan, I.

AU - Jenner, M.

AU - Calbecka, M.

AU - Dávid, M.

AU - de la Rubia, J.

AU - Drach, J.

AU - Gasztonyi, Z.

AU - Górnik, S.

AU - Leleu, X.

AU - Munder, M.

AU - Offidani, M.

AU - Zojer, N.

AU - Rajangam, K.

AU - Chang, Y. L.

AU - San-Miguel, J. F.

AU - Ludwig, H.

PY - 2016/7/15

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