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 | Clinical research Leukaemia Translational Research Basic Scientific Principles Basic Principles in the Management and Treatment (of cancer) |
| 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
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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.