ASH 2017 | Sapacitabine and decitabine administered in alternating cycles in eldery patients with newly diagnosed elderly AML: phase III SEAMLESS study 

Hagop M. Kantarjian, from The University of Texas MD Anderson Cancer Center, Houston, TX, presented data from the phase III SEAMLESS trial (NCT01303796) of sapacitabine, and decitabine, administered in alternating cycles in elderly patients with newly diagnosed AML at the 59th American Society of Hematology (ASH) Annual Meeting, Atlanta, GA, on Monday 11^th December 2017.

Sapacitabine is an orally-available nucleoside analogue that can interfere with DNA synthesis through the incorporation of CNDAC, its active metabolite, into DNA during replication, triggering a beta-elimination reaction and leading to the formation of Single-strand DNA Breaks (SSBs). During the following rounds of replication, SSBs are converted to double-strand breaks, which can lead to cell cycle arrests. Preclinical studies have demonstrated that CNDAC is synergistic with hypomethylating agents (HMAs) in AML cell lines.

In the phase III randomized SEAMLESS study, 482 patients (median age = 77 years, range, 70–90 years) were randomized to receive intravenous decitabine at 20 mg/m² per day for five consecutive days of a 4-week cycle (odd cycles) alternating with sapacitabine at 300 mg orally twice per day for three days per week for two weeks of a 4-week cycle (even cycles, [n = 241, study arm]) or decitabine monotherapy (n = 241, control arm). The primary endpoint of the study was OS.

Key data presented were:

• CR in the study and control arm: 17% vs 11%
• Median OS in the study and control arm: 5.9 vs 5.7 months, P = n.s
• Median OS in patients with < 10,000 White Blood Cell (WBC) count in the study and control arm: 8.0 vs 5.8 months, HR = 0.84, P = 0.14
• CR rate in patients with < 10,000 WBC count in the study and control arm: 21.5% vs 8.6%, P = 0.0017
• Grade <3 AEs occurred in > 10% of patients including thrombocytopenia, anemia, neutropenia, pneumonia, febrile neutropenia, sepsis and disease progression

The speaker noted that although the sapacitabine administered in alternating cycles with decitabine was well tolerated and active, but did not significantly improve the primary endpoint, OS, when compared to decitabine alone. The speaker concluded by stating that further analyses are ongoing in order to characterize the subgroups of patients who seemed to benefit from this sapacitibine plus decitabine regimen, including those with < 10,000 WBC count.