Frontline nilotinib supported for newly diagnosed CP-CML

Apr 21 2016

By Lynda Williams, Senior medwireNews Reporter

Long-term results from the ENESTnd trial indicate a favourable risk-benefit profile for frontline use of nilotinib in patients within 6 months of chronic phase-chronic myeloid leukaemia (CP-CML) diagnosis.

"Throughout the study, nilotinib has demonstrated several benefits over imatinib in surrogate endpoints of therapeutic efficacy, such as higher rates of response and lower rates of disease progression, death due to advanced CML and treatment-emergent BCR-ABL mutations", the researchers report in Leukemia.

"The risk of AEs [adverse events] (regardless of AE type) appears to be similar with nilotinib and imatinib; however, each TKI [tyrosine kinase inhibitor] is associated with different types of AEs, including a higher risk of CVEs [cardiovascular events] with nilotinib vs imatinib."

By 5 years, 77.0% of the 282 patients randomly assigned to receive nilotinib 300 mg twice daily and 77.2% of the 281 using nilotinib 400 mg twice daily achieved a major molecular response (BCR-ABL ≤0.1% on the International Scale [BCR-ABL^IS]) compared with 60.4% of the 283 patients given imatinib 400 mg once daily.

Deep molecular responses by 5 years were also more common with nilotinib 300 mg and 400 mg than with imatinib, with rates of MR⁴ (BCR-ABL^IS ≤0.01%) of 65.6%, 63.0% and 41.7%, respectively. The corresponding rates for MR^4.5 (BCR-ABL^IS ≤0.0032%) were 53.5%, 52.3% and 31.4%.

And estimated 5-year progression-free survival was 92.2%, 95.8% and 91.0% for the nilotinib 300 mg and 400 mg groups and the imatinib group, respectively. Overall survival at 5 years was estimated to be 93.7%, 96.2% and 91.7%, respectively.

None of the patients progressed to accelerated phase or blast phase during treatment. Progression after discontinuation for treatment failure occurred within 28 days for one patient given nilotinib 300 mg. Two imatinib-treated patients experienced progression more than 3 years after ending treatment, one due to failure and the other due to adverse effects.

Eighteen patients given nilotinib 300 mg died during the study, as did 10 patients given nilotinib 400 mg and 22 patients receiving imatinib, with CML the cause of death in 10 nilotinib-treated patients and 16 of the imatinib group.

Grade 3 and 4 AEs, serious AEs, and AEs leading to treatment discontinuation were comparable between the nilotinib 300 mg and imatinib treatment groups, but slightly higher in the nilotinib 400 mg group.

CVEs - defined as ischaemic heart disease, ischaemic cerebrovascular events and/or peripheral artery disease - were reported in 7.5%, 13.4% and 2.1% of the nilotinib 300 mg and 400 mg and imatinib treatment groups, respectively, and the risk increased with duration of treatment.

But analysis based on the Framingham general CV risk scores indicated that CVEs occurred most frequently in patients with a high or intermediate risk of a first CV disease event over 10 years.

"Together, our analyses and previously published data suggest that patients at risk of developing CVEs during TKI therapy might be identifiable at baseline", the researchers suggest.

The team concludes: "When choosing a frontline TKI for patients with newly diagnosed [CP-CML], physicians must consider the entire benefit-risk profile of each available option.

"Viewed as a whole, the combined efficacy and safety results from ENESTnd demonstrate that nilotinib provided patients with meaningful long-term clinical benefits over imatinib, with a positive balance of benefit and risk, particularly with the 300-mg twice-daily dose, as frontline therapy for patients with [CP-CML]."

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