ENESTnd 5-year (y) update: Long-term outcomes of patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with frontline nilotinib (NIL) versus imatinib (IM).

Abstract

7073 Background: In ENESTnd, NIL has shown superior efficacy vs IM. Here, we report data based on a minimum follow-up of 5 calendar y. Methods: Pts with newly diagnosed CML-CP were randomized to NIL 300 mg twice-daily (BID; n = 282), NIL 400 mg BID (n = 281), or IM 400 mg once-daily (QD; n = 283). P values for secondary efficacy endpoints were not adjusted for multiple comparisons and are provided for descriptive purposes only. Results: At the data cutoff, 60%, 62%, and 50% of pts in the NIL 300 mg BID, NIL 400 mg BID, and IM arms, respectively, remained on core treatment. Over half of pts in the NIL arms achieved MR4.5 (BCR-ABLIS ≤ 0.0032%) by 5 y, and MR4.5 rates were significantly higher on NIL vs IM overall and within each Sokal risk group (Table). Rates of major molecular response (MMR; BCR-ABLIS ≤ 0.1%), freedom from progression to accelerated phase/blast crisis (AP/BC), and overall survival (OS) were higher on NIL vs IM. Fewer pts treated with NIL vs IM died from advanced CML. The safety profiles of NIL and IM were as expected. The rates of cardiovascular events (CVEs) of interest remained highest on NIL 400 mg BID and lowest on IM. Conclusions: NIL continues to result in superior efficacy vs IM in pts with CML-CP. NIL was generally well tolerated; however, CVEs of interest were more common on NIL vs IM. Clinical trial information: CAMN107A2303. NIL 300 mg BID n = 282 NIL 400 mg BID n = 281 IM 400 mg QD n = 283 MR4.5 by 5 y, % (P vs IM) 54 (< .0001) 52 (< .0001) 31 Low Sokal risk 53 (.0148) 62 (.0002) 37 Intermediate Sokal risk 60 (< .0001) 50 (.0126) 33 High Sokal risk 45 (.0041) 42 (.0105) 23 MMR by 5 y, % (P vs IM) 77 (< .0001) 77 (< .0001) 60 5-y freedom from progression to AP/BC, % (P vs IM)a 96 (.0403) 98 (.0028) 92 5-y OS, % (P vs IM)a 94 (.4881) 96 (.0266) 92 Deaths from advanced CML, n (P vs IM)b 6 (.0292) 4 (.0057) 16 Safety population n = 279 n = 277 n = 280 5-y CVE rates, n (%) Ischemic heart disease 11 (4) 24 (9) 5 (2) Ischemic cerebrovascular events 4 (1) 9 (3) 1 (< 1) Peripheral artery disease 7 (3) 7 (3) 0 aKaplan-Meier estimate, including events after discontinuation. bPts for whom the principal cause of death (during treatment or follow-up) was “study indication” or “unknown” or not reported but subsequent to a documented progression to AP/BC.