Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial

Hagop M. Kantarjian, Andreas Hochhaus, Giuseppe Saglio, Carmino De Souza, Ian W. Flinn, Leif Stenke, Yeow Tee Goh, Gianantonio Rosti, Hirohisa Nakamae, Neil J. Gallagher, Albert Hoenekopp, Rick E. Blakesley, Richard A. Larson, Timothy P. Hughes

Research output: Contribution to journalArticle

331 Citations (Scopus)

Abstract

Background: Nilotinib has shown greater efficacy than imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (CML) in chronic phase after a minimum follow-up of 12 months. We present data from the Evaluating Nilotinib Efficacy and Safety in clinical Trials-newly diagnosed patients (ENESTnd) study after a minimum follow-up of 24 months. Methods: ENESTnd was a phase 3, multicentre, open-label, randomised study. Adult patients were eligible if they had been diagnosed with chronic phase, Philadelphia chromosome-positive CML within the previous 6 months. Patients were randomly assigned (1:1:1) to receive nilotinib 300 mg twice a day, nilotinib 400 mg twice a day, or imatinib 400 mg once a day, all administered orally, by use of a computer-generated randomisation schedule, using permuted blocks, and stratified according to Sokal score. Efficacy results are reported for the intention-to-treat population. The primary endpoint was major molecular response at 12 months, defined as BCR-ABL transcript levels on the International Scale (BCR-ABLIS) of 0·1% or less by real-time quantitative PCR in peripheral blood. This study is registered with ClinicalTrials.gov, number NCT00471497. Findings: 282 patients were randomly assigned to receive nilotinib 300 mg twice daily, 281 to receive nilotinib 400 mg twice daily, and 283 to receive imatinib. By 24 months, significantly more patients had a major molecular response with nilotinib than with imatinib (201 [71%] with nilotinib 300 mg twice daily, 187 [67%] with nilotinib 400 mg twice daily, and 124 [44%] with imatinib; p<0·0001 for both comparisons). Significantly more patients in the nilotinib groups achieved a complete molecular response (defined as a reduction of BCR-ABLIS levels to ≤0·0032%) at any time than did those in the imatinib group (74 [26%] with nilotinib 300 mg twice daily, 59 [21%] with nilotinib 400 mg twice daily, and 29 [10%] with imatinib; p<0·0001 for nilotinib 300 mg twice daily vs imatinib, p=0·0004 for nilotinib 400 mg twice daily vs imatinib). There were fewer progressions to accelerated or blast phase on treatment, including clonal evolution, in the nilotinib groups than in the imatinib group (two with nilotinib 300 mg twice daily, five with nilotinib 400 mg twice daily, and 17 with imatinib; p=0·0003 for nilotinib 300 mg twice daily vs imatinib, p=0·0089 for nilotinib 400 mg twice daily vs imatinib). At 24 months, survival was comparable in all treatment groups, but fewer CML-related deaths had occurred in both the nilotinib groups than in the imatinib group (five with nilotinib 300 mg twice daily, three with nilotinib 400 mg twice daily, and ten with imatinib). Overall, the only grade 3 or 4 non-haematological adverse events that occurred in at least 2·5% of patients were headache (eight [3%] with nilotinib 300 mg twice daily, four [1%] with nilotinib 400 mg twice daily, and two [<1%] with imatinib) and rash (two [<1%], seven [3%], and five [2%], respectively). Grade 3 or 4 neutropenia was more common with imatinib than with either dose of nilotinib (33 [12%] with nilotinib 300 mg twice daily, 30 [11%] with nilotinib 400 mg twice daily, and 59 [21%] with imatinib). Serious adverse events were reported in eight additional patients in the second year of the study (four with nilotinib 300 mg twice daily, three with nilotinib 400 mg twice daily, and one with imatinib). Interpretation: Nilotinib continues to show better efficacy than imatinib for the treatment of patients with newly diagnosed CML in chronic phase. These results support nilotinib as a first-line treatment option for patients with newly diagnosed disease. Funding: Novartis.

LanguageEnglish
Pages841-851
Number of pages11
JournalThe Lancet Oncology
Volume12
Issue number9
DOIs
Publication statusPublished - 1 Sep 2011

ASJC Scopus subject areas

  • Oncology

Cite this

Kantarjian, Hagop M. ; Hochhaus, Andreas ; Saglio, Giuseppe ; Souza, Carmino De ; Flinn, Ian W. ; Stenke, Leif ; Goh, Yeow Tee ; Rosti, Gianantonio ; Nakamae, Hirohisa ; Gallagher, Neil J. ; Hoenekopp, Albert ; Blakesley, Rick E. ; Larson, Richard A. ; Hughes, Timothy P. / Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia : 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. In: The Lancet Oncology. 2011 ; Vol. 12, No. 9. pp. 841-851.
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title = "Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial",
abstract = "Background: Nilotinib has shown greater efficacy than imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (CML) in chronic phase after a minimum follow-up of 12 months. We present data from the Evaluating Nilotinib Efficacy and Safety in clinical Trials-newly diagnosed patients (ENESTnd) study after a minimum follow-up of 24 months. Methods: ENESTnd was a phase 3, multicentre, open-label, randomised study. Adult patients were eligible if they had been diagnosed with chronic phase, Philadelphia chromosome-positive CML within the previous 6 months. Patients were randomly assigned (1:1:1) to receive nilotinib 300 mg twice a day, nilotinib 400 mg twice a day, or imatinib 400 mg once a day, all administered orally, by use of a computer-generated randomisation schedule, using permuted blocks, and stratified according to Sokal score. Efficacy results are reported for the intention-to-treat population. The primary endpoint was major molecular response at 12 months, defined as BCR-ABL transcript levels on the International Scale (BCR-ABLIS) of 0·1{\%} or less by real-time quantitative PCR in peripheral blood. This study is registered with ClinicalTrials.gov, number NCT00471497. Findings: 282 patients were randomly assigned to receive nilotinib 300 mg twice daily, 281 to receive nilotinib 400 mg twice daily, and 283 to receive imatinib. By 24 months, significantly more patients had a major molecular response with nilotinib than with imatinib (201 [71{\%}] with nilotinib 300 mg twice daily, 187 [67{\%}] with nilotinib 400 mg twice daily, and 124 [44{\%}] with imatinib; p<0·0001 for both comparisons). Significantly more patients in the nilotinib groups achieved a complete molecular response (defined as a reduction of BCR-ABLIS levels to ≤0·0032{\%}) at any time than did those in the imatinib group (74 [26{\%}] with nilotinib 300 mg twice daily, 59 [21{\%}] with nilotinib 400 mg twice daily, and 29 [10{\%}] with imatinib; p<0·0001 for nilotinib 300 mg twice daily vs imatinib, p=0·0004 for nilotinib 400 mg twice daily vs imatinib). There were fewer progressions to accelerated or blast phase on treatment, including clonal evolution, in the nilotinib groups than in the imatinib group (two with nilotinib 300 mg twice daily, five with nilotinib 400 mg twice daily, and 17 with imatinib; p=0·0003 for nilotinib 300 mg twice daily vs imatinib, p=0·0089 for nilotinib 400 mg twice daily vs imatinib). At 24 months, survival was comparable in all treatment groups, but fewer CML-related deaths had occurred in both the nilotinib groups than in the imatinib group (five with nilotinib 300 mg twice daily, three with nilotinib 400 mg twice daily, and ten with imatinib). Overall, the only grade 3 or 4 non-haematological adverse events that occurred in at least 2·5{\%} of patients were headache (eight [3{\%}] with nilotinib 300 mg twice daily, four [1{\%}] with nilotinib 400 mg twice daily, and two [<1{\%}] with imatinib) and rash (two [<1{\%}], seven [3{\%}], and five [2{\%}], respectively). Grade 3 or 4 neutropenia was more common with imatinib than with either dose of nilotinib (33 [12{\%}] with nilotinib 300 mg twice daily, 30 [11{\%}] with nilotinib 400 mg twice daily, and 59 [21{\%}] with imatinib). Serious adverse events were reported in eight additional patients in the second year of the study (four with nilotinib 300 mg twice daily, three with nilotinib 400 mg twice daily, and one with imatinib). Interpretation: Nilotinib continues to show better efficacy than imatinib for the treatment of patients with newly diagnosed CML in chronic phase. These results support nilotinib as a first-line treatment option for patients with newly diagnosed disease. Funding: Novartis.",
author = "Kantarjian, {Hagop M.} and Andreas Hochhaus and Giuseppe Saglio and Souza, {Carmino De} and Flinn, {Ian W.} and Leif Stenke and Goh, {Yeow Tee} and Gianantonio Rosti and Hirohisa Nakamae and Gallagher, {Neil J.} and Albert Hoenekopp and Blakesley, {Rick E.} and Larson, {Richard A.} and Hughes, {Timothy P.}",
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Kantarjian, HM, Hochhaus, A, Saglio, G, Souza, CD, Flinn, IW, Stenke, L, Goh, YT, Rosti, G, Nakamae, H, Gallagher, NJ, Hoenekopp, A, Blakesley, RE, Larson, RA & Hughes, TP 2011, 'Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia: 24-month minimum follow-up of the phase 3 randomised ENESTnd trial', The Lancet Oncology, vol. 12, no. 9, pp. 841-851. https://doi.org/10.1016/S1470-2045(11)70201-7

Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia : 24-month minimum follow-up of the phase 3 randomised ENESTnd trial. / Kantarjian, Hagop M.; Hochhaus, Andreas; Saglio, Giuseppe; Souza, Carmino De; Flinn, Ian W.; Stenke, Leif; Goh, Yeow Tee; Rosti, Gianantonio; Nakamae, Hirohisa; Gallagher, Neil J.; Hoenekopp, Albert; Blakesley, Rick E.; Larson, Richard A.; Hughes, Timothy P.

In: The Lancet Oncology, Vol. 12, No. 9, 01.09.2011, p. 841-851.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nilotinib versus imatinib for the treatment of patients with newly diagnosed chronic phase, Philadelphia chromosome-positive, chronic myeloid leukaemia

T2 - The Lancet Oncology

AU - Kantarjian, Hagop M.

AU - Hochhaus, Andreas

AU - Saglio, Giuseppe

AU - Souza, Carmino De

AU - Flinn, Ian W.

AU - Stenke, Leif

AU - Goh, Yeow Tee

AU - Rosti, Gianantonio

AU - Nakamae, Hirohisa

AU - Gallagher, Neil J.

AU - Hoenekopp, Albert

AU - Blakesley, Rick E.

AU - Larson, Richard A.

AU - Hughes, Timothy P.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Background: Nilotinib has shown greater efficacy than imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (CML) in chronic phase after a minimum follow-up of 12 months. We present data from the Evaluating Nilotinib Efficacy and Safety in clinical Trials-newly diagnosed patients (ENESTnd) study after a minimum follow-up of 24 months. Methods: ENESTnd was a phase 3, multicentre, open-label, randomised study. Adult patients were eligible if they had been diagnosed with chronic phase, Philadelphia chromosome-positive CML within the previous 6 months. Patients were randomly assigned (1:1:1) to receive nilotinib 300 mg twice a day, nilotinib 400 mg twice a day, or imatinib 400 mg once a day, all administered orally, by use of a computer-generated randomisation schedule, using permuted blocks, and stratified according to Sokal score. Efficacy results are reported for the intention-to-treat population. The primary endpoint was major molecular response at 12 months, defined as BCR-ABL transcript levels on the International Scale (BCR-ABLIS) of 0·1% or less by real-time quantitative PCR in peripheral blood. This study is registered with ClinicalTrials.gov, number NCT00471497. Findings: 282 patients were randomly assigned to receive nilotinib 300 mg twice daily, 281 to receive nilotinib 400 mg twice daily, and 283 to receive imatinib. By 24 months, significantly more patients had a major molecular response with nilotinib than with imatinib (201 [71%] with nilotinib 300 mg twice daily, 187 [67%] with nilotinib 400 mg twice daily, and 124 [44%] with imatinib; p<0·0001 for both comparisons). Significantly more patients in the nilotinib groups achieved a complete molecular response (defined as a reduction of BCR-ABLIS levels to ≤0·0032%) at any time than did those in the imatinib group (74 [26%] with nilotinib 300 mg twice daily, 59 [21%] with nilotinib 400 mg twice daily, and 29 [10%] with imatinib; p<0·0001 for nilotinib 300 mg twice daily vs imatinib, p=0·0004 for nilotinib 400 mg twice daily vs imatinib). There were fewer progressions to accelerated or blast phase on treatment, including clonal evolution, in the nilotinib groups than in the imatinib group (two with nilotinib 300 mg twice daily, five with nilotinib 400 mg twice daily, and 17 with imatinib; p=0·0003 for nilotinib 300 mg twice daily vs imatinib, p=0·0089 for nilotinib 400 mg twice daily vs imatinib). At 24 months, survival was comparable in all treatment groups, but fewer CML-related deaths had occurred in both the nilotinib groups than in the imatinib group (five with nilotinib 300 mg twice daily, three with nilotinib 400 mg twice daily, and ten with imatinib). Overall, the only grade 3 or 4 non-haematological adverse events that occurred in at least 2·5% of patients were headache (eight [3%] with nilotinib 300 mg twice daily, four [1%] with nilotinib 400 mg twice daily, and two [<1%] with imatinib) and rash (two [<1%], seven [3%], and five [2%], respectively). Grade 3 or 4 neutropenia was more common with imatinib than with either dose of nilotinib (33 [12%] with nilotinib 300 mg twice daily, 30 [11%] with nilotinib 400 mg twice daily, and 59 [21%] with imatinib). Serious adverse events were reported in eight additional patients in the second year of the study (four with nilotinib 300 mg twice daily, three with nilotinib 400 mg twice daily, and one with imatinib). Interpretation: Nilotinib continues to show better efficacy than imatinib for the treatment of patients with newly diagnosed CML in chronic phase. These results support nilotinib as a first-line treatment option for patients with newly diagnosed disease. Funding: Novartis.

AB - Background: Nilotinib has shown greater efficacy than imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukaemia (CML) in chronic phase after a minimum follow-up of 12 months. We present data from the Evaluating Nilotinib Efficacy and Safety in clinical Trials-newly diagnosed patients (ENESTnd) study after a minimum follow-up of 24 months. Methods: ENESTnd was a phase 3, multicentre, open-label, randomised study. Adult patients were eligible if they had been diagnosed with chronic phase, Philadelphia chromosome-positive CML within the previous 6 months. Patients were randomly assigned (1:1:1) to receive nilotinib 300 mg twice a day, nilotinib 400 mg twice a day, or imatinib 400 mg once a day, all administered orally, by use of a computer-generated randomisation schedule, using permuted blocks, and stratified according to Sokal score. Efficacy results are reported for the intention-to-treat population. The primary endpoint was major molecular response at 12 months, defined as BCR-ABL transcript levels on the International Scale (BCR-ABLIS) of 0·1% or less by real-time quantitative PCR in peripheral blood. This study is registered with ClinicalTrials.gov, number NCT00471497. Findings: 282 patients were randomly assigned to receive nilotinib 300 mg twice daily, 281 to receive nilotinib 400 mg twice daily, and 283 to receive imatinib. By 24 months, significantly more patients had a major molecular response with nilotinib than with imatinib (201 [71%] with nilotinib 300 mg twice daily, 187 [67%] with nilotinib 400 mg twice daily, and 124 [44%] with imatinib; p<0·0001 for both comparisons). Significantly more patients in the nilotinib groups achieved a complete molecular response (defined as a reduction of BCR-ABLIS levels to ≤0·0032%) at any time than did those in the imatinib group (74 [26%] with nilotinib 300 mg twice daily, 59 [21%] with nilotinib 400 mg twice daily, and 29 [10%] with imatinib; p<0·0001 for nilotinib 300 mg twice daily vs imatinib, p=0·0004 for nilotinib 400 mg twice daily vs imatinib). There were fewer progressions to accelerated or blast phase on treatment, including clonal evolution, in the nilotinib groups than in the imatinib group (two with nilotinib 300 mg twice daily, five with nilotinib 400 mg twice daily, and 17 with imatinib; p=0·0003 for nilotinib 300 mg twice daily vs imatinib, p=0·0089 for nilotinib 400 mg twice daily vs imatinib). At 24 months, survival was comparable in all treatment groups, but fewer CML-related deaths had occurred in both the nilotinib groups than in the imatinib group (five with nilotinib 300 mg twice daily, three with nilotinib 400 mg twice daily, and ten with imatinib). Overall, the only grade 3 or 4 non-haematological adverse events that occurred in at least 2·5% of patients were headache (eight [3%] with nilotinib 300 mg twice daily, four [1%] with nilotinib 400 mg twice daily, and two [<1%] with imatinib) and rash (two [<1%], seven [3%], and five [2%], respectively). Grade 3 or 4 neutropenia was more common with imatinib than with either dose of nilotinib (33 [12%] with nilotinib 300 mg twice daily, 30 [11%] with nilotinib 400 mg twice daily, and 59 [21%] with imatinib). Serious adverse events were reported in eight additional patients in the second year of the study (four with nilotinib 300 mg twice daily, three with nilotinib 400 mg twice daily, and one with imatinib). Interpretation: Nilotinib continues to show better efficacy than imatinib for the treatment of patients with newly diagnosed CML in chronic phase. These results support nilotinib as a first-line treatment option for patients with newly diagnosed disease. Funding: Novartis.

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