947O - Comparison of efficacy and safety of 5-day and 10-day schedules of SGI-110, a novel subcutaneous (SC) hypomethylating agent (HMA), in the treatment...

Date 29 September 2014
Event ESMO 2014
Session Haematological malignancies
Topics Drug Development
Leukaemia
Translational Research
Presenter Gail Roboz
Citation Annals of Oncology (2014) 25 (suppl_4): iv327-iv339. 10.1093/annonc/mdu339
Authors G.J. Roboz1, F. Ravandi2, P. Kropf3, K. Yee4, C. O'Connell5, E. Griffiths6, W. Stock7, G. Garcia-Manero2, E. Jabbour2, N. Daver2, N. Pemmaraju2, J. Issa8, K. Walsh9, D. Rizzieri10, S. Lunin11, S. Naim12, Y. Hao12, M. Azab13, H. Kantarjian2
  • 1Medicine, Weill Cornell Medical College, 10021 - New York/US
  • 2Leukemia, UT MD Anderson Cancer Center, Houston/US
  • 3Bmt Program, Fox Chase Cancer Center, Philadelphia/US
  • 4Leukemia, Princess Margaret Cancer Center, Toronto/CA
  • 5Hematology, University of Southern California, Keck School of Medicine, Los Angeles/US
  • 6Leukemia, Roswell Park Cancer Institute, Buffalo/US
  • 7Leukemia, The University of Chicago Medical Center, Chicago/US
  • 8Medicine, Fels Institute, Temple University, Philadelphia/US
  • 9Leukemia, The Ohio State University, Columbus/US
  • 10Hematologic Malignancies, Duke University Medical Center, Raleigh/US
  • 11Hematology, Florida Cancer Specialist and Research Institute, Fort Myers/US
  • 12Clinical Development, Astex Pharmaceuticals, Inc., 94568 - Dublin/US
  • 13Clinical Development, Astex Pharmaceutials, Inc., 94568 - Dublin/US

Abstract

Aim

SGI-110 SC is a novel HMA that delivers prolonged decitabine exposure and potent DNA demethylation. Preliminary results of two different schedules (5 and 10-days every 28-days) in the treatment of r/r AML have been previously reported. Here we provide a comparative analysis of final results from the two schedules.

Methods

Heavily pretreated r/r AML patients were treated in a single protocol by the same centers. Enrolment to the 5-day schedule was completed first (at 60 and 90 mg/m2/d) followed by enrolment to the 10-day schedule at 60 mg/m2/d. In the 10-day schedule, patients were allowed up to 4 cycles followed by consolidation with the 5-day schedule at 60 mg/m2/d. The primary endpoint was Overall Complete Response (OCR = CR + CRp + CRi) using revised IWG 2003 criteria.

Results

Fifty and 53 patients were treated with the 5-day and 10-day schedules respectively. Baseline patients' characteristics were similar between the 2 schedules including median number of prior regimens (2); median age 62 vs 57 y; ECOG PS 2 in 10 vs 17%; median WBC count 1.7 vs 2.1x109/L; median bone marrow blasts 35 vs 32% for the 5 and 10-day schedules respectively. OCR was reported in 8 (16%) and 16 patients (30%) [P = 0.106] and CR was reported in 3 (6%) vs 10 patients (19%) [P =0.074] for the 5 and 10-day schedules respectively. The most common Grade ≥3 adverse events (AEs) regardless of relationship to treatment were febrile neutropenia: 60% vs 58%; thrombocytopenia: 20% vs 38% (P =0.054); anemia: 18 %vs 36% (P =0.049); and pneumonia: 24% vs 28% (P =0.660) for the 5 and 10-day schedules respectively. All-cause early mortality was similar at 30 days: 6% vs 2%, and at 60 days: 12% vs 11% for the 5 and 10-day schedules respectively.

Conclusions

SGI-110 given SC for 10 days resulted in a trend towards higher OCR and CR rates than the 5-day schedule, albeit with a higher incidence of Grade ≥3 thrombocytopenia and anemia but no significant differences in other common Grade ≥3 AEs or all-cause early mortality. These results warrant further investigation of the 10-day schedule for the treatment of r/r AML and newly diagnosed elderly AML.

Disclosure

G.J. Roboz: consultant for Astex; K. Yee: Astex Grant/Research support; E. Griffiths: Astex: Grants/Research Support Recipient; Advisor/Board Member Celegene: Consultant/Independent Contractor Honorarium Recipient; J. Issa: consultant and research support from Astex; S. Naim: Astex employee; Y. Hao and M. Azab: Astex employee. All other authors have declared no conflicts of interest.