PF293 PHASE 3 EXPLORATORY ANALYSIS OF OUTCOMES IN OLDER ADULTS WITH NEWLY DIAGNOSED, HIGH‐RISK/SECONDARY AML WHO ACHIEVED REMISSION WITH CPX‐351 VERSUS 7+3 INDUCTION

Abstract

Background:CPX‐351 (Vyxeos®; daunorubicin and cytarabine powder for concentrate for solution for infusion), a dual‐drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio, is approved by the EMA and US FDA for the treatment of adults with newly diagnosed, therapy‐related AML or AML with myelodysplasia‐related changes. In a randomized phase 3 study, induction followed by consolidation with CPX‐351 significantly improved median overall survival (OS) versus conventional 7+3 cytarabine/daunorubicin chemotherapy (9.56 vs 5.95 months; HR = 0.69 [95% CI: 0.52–0.90; 1‐sided P = 0.003) and had a safety profile comparable to 7+3 in adults aged 60–75 years with newly diagnosed, high‐risk/secondary AML (Lancet, et al. J Clin Oncol 2018). CPX‐351 was also associated with significantly higher rates versus 7+3 of complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CR+CRi; 73/153 [48%] vs 52/156 [33%]; OR = 1.77 [95% CI: 1.11–2.81]; 2‐sided P = 0.016) and CR (57/153 [37%] vs 40/156 [26%]; OR = 1.69 [95% CI: 1.03–2.78]; 2‐sided P = 0.040).Aims:This exploratory analysis of the phase 3 study evaluated outcomes in the subgroup of patients (pts) who achieved CR+CRi following induction with CPX‐351 versus 7+3.Methods:A total of 309 pts were randomized 1:1 to receive up to 2 induction cycles of CPX‐351 (100 units/m2 [daunorubicin 44 mg/m2 + cytarabine 100 mg/m2] on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (cytarabine 100 mg/m2/day continuously for 7 days [2nd induction: 5 days] + daunorubicin 60 mg/m2 on Days 1–3 [2nd induction: Days 1–2]). Pts achieving CR+CRi could receive up to 2 consolidation cycles with CPX‐351 (65 units/m2 [daunorubicin 29 mg/m2 + cytarabine 65 mg/m2] on Days 1 and 3) or 5+2 (as for 2nd induction). For this analysis, outcomes were evaluated in the subgroup of pts who achieved CR+CRi following induction.Results:Baseline characteristics of pts who achieved CR+CRi were generally balanced between arms. Median OS was longer with CPX‐351 versus 7+3 in pts who achieved CR+CRi (25.43 vs 10.41 months; HR = 0.49 [95% CI: 0.31–0.77]) or CR (25.43 vs 10.97 months; HR = 0.49 [95% CI: 0.29–0.83]; Figure 1). Of pts who achieved CR+CRi, 40/73 (55%) in the CPX‐351 arm and 24/52 (46%) in the 7+3 arm underwent transplantation (OR = 0.71 [95% CI: 0.35–1.44]; median OS landmarked from the date of transplant was not reached versus 11.65 months, respectively (HR = 0.42 [95% CI: 0.20–0.86]; Figure 2). Serious treatment‐emergent adverse events in ≥5% of pts who achieved CR+CRi were febrile neutropenia (CPX‐351: 15%; 7+3: 12%), acute respiratory failure (7%; 2%), ejection fraction decreased (5%; 4%), sepsis (5%; 4%), pneumonia (3%; 6%), and pulmonary edema (1%; 6%). Four pts with CR+CRi died during the treatment phase (sepsis [CPX‐351]; atrial fibrillation [7+3]; disease progression [7+3]; intracranial hemorrhage [7+3]); no patient experienced early mortality (within 60 days) in either arm. Median time for recovery to neutrophils ≥1,000/μL and platelets ≥100,000/μL, respectively, in pts who achieved CR+CRi was longer with CPX‐351 (37 and 42 days) versus 7+3 (29 and 32 days).Summary/Conclusion:Among pts who achieved CR+CRi in this study, those who received CPX‐351 had longer median OS, a higher rate of transplantation, and longer median OS landmarked from the date of transplant versus 7+3, suggesting potentially deeper responses may be achieved with CPX‐351. The safety profile of CPX‐351 in pts who achieved CR+CRi was consistent with the known profile of 7+3, as well as the overall study population.image