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Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS)

Kantarjian, Hagop M. ; Begna, Kebede H. ; Altman, Jessica K. ; Goldberg, Stuart L. ; Sekeres, Mikkael A. ; Strickland, Stephen A. ; Arellano, Martha L. ; Claxton, David F. ; Baer, Maria R. ; Gautier, Marc ; Berman, Ellin ; Seiter, Karen ; Solomon, Scott R. ; Schiller, Gary J. ; Luger, Selina M. ; Butrym, Aleksandra ; Gaidano, Gianluca ; Thomas, Xavier G. ; Montesinos, Pau ; Rizzieri, David A. ; Quick, Donald P. ; Venugopal, Parameswaran ; Gaur, Rakesh ; Maness, Lori J. ; Kadia, Tapan M. ; Ravandi, Farhad ; Buyse, Marc E. ; Chiao, Judy H.

Cancer, 2021-12, Vol.127 (23), p.4421-4431 [Periódico revisado por pares]

United States: Wiley Subscription Services, Inc

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  • Título:
    Results of a randomized phase 3 study of oral sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia (SEAMLESS)
  • Autor: Kantarjian, Hagop M. ; Begna, Kebede H. ; Altman, Jessica K. ; Goldberg, Stuart L. ; Sekeres, Mikkael A. ; Strickland, Stephen A. ; Arellano, Martha L. ; Claxton, David F. ; Baer, Maria R. ; Gautier, Marc ; Berman, Ellin ; Seiter, Karen ; Solomon, Scott R. ; Schiller, Gary J. ; Luger, Selina M. ; Butrym, Aleksandra ; Gaidano, Gianluca ; Thomas, Xavier G. ; Montesinos, Pau ; Rizzieri, David A. ; Quick, Donald P. ; Venugopal, Parameswaran ; Gaur, Rakesh ; Maness, Lori J. ; Kadia, Tapan M. ; Ravandi, Farhad ; Buyse, Marc E. ; Chiao, Judy H.
  • Assuntos: 5-aza-2'-deoxycytidine ; Acute myeloid leukemia ; acute myeloid leukemia (AML) ; Aged ; Arabinonucleosides ; Azacitidine ; Blood ; Bone marrow ; Chemotherapy ; Cytosine - analogs & derivatives ; Cytosine - therapeutic use ; Decitabine ; Disorders ; Erythrocytes ; Humans ; hypomethylation ; Intravenous administration ; Leukemia ; Leukemia, Myeloid, Acute ; Myelodysplastic syndrome ; Myeloid leukemia ; Neoplasms ; Nucleoside analogs ; Older people ; Oral administration ; Randomization ; Remission ; Remission (Medicine) ; sapacitabine ; Subgroups ; Survival ; therapy ; Transfusion ; Treatment Outcome ; Tumors ; White blood cells
  • É parte de: Cancer, 2021-12, Vol.127 (23), p.4421-4431
  • Notas: Scott R. Solomon: Concept, data, analysis, investigation, writing original/review.
    Gianluca Gaidano: Concept, data, analysis, investigation, writing original/review.
    Maria R. Baer: Concept, data, analysis, investigation, writing original/review.
    David Rizzieri: Concept, data, analysis, investigation, writing original/review.
    Gary J. Schiller: Concept, data, analysis, investigation, writing original/review.
    Martha Arellano: Concept, data, analysis, investigation, writing original/review.
    Parameswaran Venugopal: Concept, data, analysis, investigation, writing original/review.
    Selina Luger: Concept, data, analysis, investigation, writing original/review.
    Current affiliation: Advent Health System Cancer Center, Shawnee Mission, KS
    Marc Buyse: Concept, data, analysis, investigation, writing original/review.
    Stuart Goldberg: Concept, data, analysis, investigation, writing original/review.
    Tapan M. Kadia: Concept, data, analysis, investigation, writing original/review.
    Ellin Berman: Concept, data, analysis, investigation, writing original/review.
    Marc Gautier: Concept, data, analysis, investigation, writing original/review.
    Farhad Ravandi: Concept, data, analysis, investigation, writing original/review.
    Karen Seiter: Concept, data, analysis, investigation, writing original/review.
    David Claxton: Concept, data, analysis, investigation, writing original/review.
    Xavier Thomas: Concept, data, analysis, investigation, writing original/review.
    Hagop M. Kantarjian: conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing-original draft and writing-review and editing.
    Author Contributions
    Paul Montesinos: Concept, data, analysis, investigation, writing original/review.
    Aleksandra Butrym: Concept, data, analysis, investigation, writing original/review.
    Jessica K. Altman: Concept, data, analysis, investigation, writing original/review.
    Mikkael A. Sekeres: Concept, data, analysis, investigation, writing original/review.
    Rakesh Gaur: Concept, data, analysis, investigation, writing original/review.
    Stephen Strickland: Concept, data, analysis, investigation, writing original/review.
    Kebede Begna: Concept, data, analysis, investigation, writing original/review.
    Donald Quick: Concept, data, analysis, investigation, writing original/review.
    Judy H. Chiao: conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, software, supervision, validation, visualization, writing-original draft and writing-review and editing.
    Lori J. Maness: Concept, data, analysis, investigation, writing original/review.
  • Descrição: Background Acute myeloid leukemia (AML) is fatal in elderly patients who are unfit for standard induction chemotherapy. The objective of this study was to evaluate the survival benefit of administering sapacitabine, an oral nucleoside analogue, in alternating cycles with decitabine, a low‐intensity therapy, to elderly patients with newly diagnosed AML. Methods This randomized, open‐label, phase 3 study (SEAMLESS) was conducted at 87 sites in 11 countries. Patients aged ≥70 years who were not candidates for or chose not to receive standard induction chemotherapy were randomized 1:1 to arm A (decitabine in alternating cycles with sapacitabine) received 1‐hour intravenous infusions of decitabine 20 mg/m2 once daily for 5 consecutive days every 8 weeks (first cycle and subsequent odd cycles) and sapacitabine 300 mg twice daily on 3 consecutive days per week for 2 weeks every 8 weeks (second cycle and subsequent even cycles) or to control arm C who received 1‐hour infusions of decitabine 20 mg/m2 once daily for 5 consecutive days every 4 weeks. Prior hypomethylating agent therapy for preexisting myelodysplastic syndromes or myeloproliferative neoplasms was an exclusion criterion. Randomization was stratified by antecedent myelodysplastic syndromes or myeloproliferative neoplasms, white blood cell count (<10 × 109/L and ≥10 × 109/L), and bone marrow blast percentage (≥50% vs <50%). The primary end point was overall survival (OS). Secondary end points were the rates of complete remission (CR), CR with incomplete platelet count recovery, partial remission, hematologic improvement, and stable disease along with the corresponding durations, transfusion requirements, number of hospitalized days, and 1‐year survival. The trial is registered at ClinicalTrials.gov (NCT01303796). Results Between October 2011 and December 2014, 482 patients were enrolled and randomized to receive decitabine administered in alternating cycles with sapacitabine (study arm, n = 241) or decitabine monotherapy (control arm, n = 241). The median OS was 5.9 months on the study arm versus 5.7 months on the control arm (P = .8902). The CR rate was 16.6% on the study arm and 10.8% on the control arm (P = .1468). In patients with white blood cell counts <10 × 109/L (n = 321), the median OS was higher on the study arm versus the control arm (8.0 vs 5.8 months; P = .145), as was the CR rate (21.5% vs 8.6%; P = .0017). Conclusions The regimen of decitabine administered in alternating cycles with sapacitabine was active but did not significantly improve OS compared with decitabine monotherapy. Subgroup analyses suggest that patients with baseline white blood cell counts <10 × 109/L might benefit from decitabine alternating with sapacitabine, with an improved CR rate and the convenience of an oral drug. These findings should be prospectively confirmed. The regimen of decitabine administered in alternating cycles with sapacitabine is active but does not significantly improve overall survival compared with decitabine monotherapy. Subgroup analyses suggest that patients with baseline white blood cell counts <10 × 109/L might benefit from decitabine alternating with sapacitabine, which has an improved complete remission rate and the convenience of an oral drug; these findings should be prospectively confirmed.
  • Editor: United States: Wiley Subscription Services, Inc
  • Idioma: Inglês
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