Phase III clinical trial (RERISE study) results of efficacy and safety of radotinib compared with imatinib in newly diagnosed chronic phase chronic myeloid leukemia

Jae Yong Kwak, Sung Hyun Kim, Suk Joong Oh, Dae Young Zang, Hawk Kim, Jeong A. Kim, Young Rok Do, Hyeoung Joon Kim, Joon Seong Park, Chul Won Choi, Won Sik Lee, Yeung Chul Mun, Jee Hyun Kong, Joo Seop Chung, Ho Jin Shin, Dae Young Kim, Jinny Park, Chul Won Jung, Udomsak Bunworasate, Narcisa Sonia ComiaSaengsuree Jootar, Arry Harryanto Reksodiputro, Priscilla B. Caguioa, Sung Eun Lee, Dong Wook Kim

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Abstract

Purpose: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for chronic phase chronic myeloid leukemia (CML-CP) in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP. Experimental Design: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily radotinib doses, or imatinib daily. The primary endpoint was major molecular response (MMR) by 12 months. Results: Two hundred forty-one patients were randomized to receive radotinib 300 mg (n ¼ 79) or 400 mg twice-daily (n ¼ 81), or imatinib 400 mg daily (n ¼ 81). MMR rates by 12 months were higher in patients receiving radotinib 300 mg (52%) or radotinib 400 mg twice-daily (46%) versus imatinib (30%; P ¼ 0.0044 and P ¼ 0.0342, respectively). Complete cytogenetic response (CCyR) rates by 12 months were higher for radotinib 300 mg (91%) versus imatinib (77%; P ¼ 0.0120). Early molecular response at 3 months occurred in 86% and 87% of patients receiving radotinib 300 mg and radotinib 400 mg, respectively, and 71% of those receiving imatinib. By 12 months, no patients had progression to accelerated phase or blast crisis. Most adverse events were manageable with dose reduction. Conclusions: Radotinib demonstrated superiority over imatinib in CCyR and MMR in patients newly diagnosed with Philadelphia chromosome–positive CML-CP. This trial was registered at www.clinicaltrials.gov as NCT01511289.

Original languageEnglish
Pages (from-to)7180-7188
Number of pages9
JournalClinical Cancer Research
Volume23
Issue number23
DOIs
Publication statusPublished - 2017 Dec 1

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Leukemia, Myeloid, Chronic Phase
Phase III Clinical Trials
Safety
Cytogenetics
4-methyl-N-(3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl)-3-(4-pyrazin-2-ylpyrimidin-2-ylamino)benzamide
Imatinib Mesylate
Blast Crisis
Korea
Protein-Tyrosine Kinases
Research Design

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Phase III clinical trial (RERISE study) results of efficacy and safety of radotinib compared with imatinib in newly diagnosed chronic phase chronic myeloid leukemia. / Kwak, Jae Yong; Kim, Sung Hyun; Oh, Suk Joong; Zang, Dae Young; Kim, Hawk; Kim, Jeong A.; Do, Young Rok; Kim, Hyeoung Joon; Park, Joon Seong; Choi, Chul Won; Lee, Won Sik; Mun, Yeung Chul; Kong, Jee Hyun; Chung, Joo Seop; Shin, Ho Jin; Kim, Dae Young; Park, Jinny; Jung, Chul Won; Bunworasate, Udomsak; Comia, Narcisa Sonia; Jootar, Saengsuree; Reksodiputro, Arry Harryanto; Caguioa, Priscilla B.; Lee, Sung Eun; Kim, Dong Wook.

In: Clinical Cancer Research, Vol. 23, No. 23, 01.12.2017, p. 7180-7188.

Research output: Contribution to journalArticle

Kwak, JY, Kim, SH, Oh, SJ, Zang, DY, Kim, H, Kim, JA, Do, YR, Kim, HJ, Park, JS, Choi, CW, Lee, WS, Mun, YC, Kong, JH, Chung, JS, Shin, HJ, Kim, DY, Park, J, Jung, CW, Bunworasate, U, Comia, NS, Jootar, S, Reksodiputro, AH, Caguioa, PB, Lee, SE & Kim, DW 2017, 'Phase III clinical trial (RERISE study) results of efficacy and safety of radotinib compared with imatinib in newly diagnosed chronic phase chronic myeloid leukemia', Clinical Cancer Research, vol. 23, no. 23, pp. 7180-7188. https://doi.org/10.1158/1078-0432.CCR-17-0957
Kwak, Jae Yong ; Kim, Sung Hyun ; Oh, Suk Joong ; Zang, Dae Young ; Kim, Hawk ; Kim, Jeong A. ; Do, Young Rok ; Kim, Hyeoung Joon ; Park, Joon Seong ; Choi, Chul Won ; Lee, Won Sik ; Mun, Yeung Chul ; Kong, Jee Hyun ; Chung, Joo Seop ; Shin, Ho Jin ; Kim, Dae Young ; Park, Jinny ; Jung, Chul Won ; Bunworasate, Udomsak ; Comia, Narcisa Sonia ; Jootar, Saengsuree ; Reksodiputro, Arry Harryanto ; Caguioa, Priscilla B. ; Lee, Sung Eun ; Kim, Dong Wook. / Phase III clinical trial (RERISE study) results of efficacy and safety of radotinib compared with imatinib in newly diagnosed chronic phase chronic myeloid leukemia. In: Clinical Cancer Research. 2017 ; Vol. 23, No. 23. pp. 7180-7188.
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abstract = "Purpose: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for chronic phase chronic myeloid leukemia (CML-CP) in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP. Experimental Design: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily radotinib doses, or imatinib daily. The primary endpoint was major molecular response (MMR) by 12 months. Results: Two hundred forty-one patients were randomized to receive radotinib 300 mg (n ¼ 79) or 400 mg twice-daily (n ¼ 81), or imatinib 400 mg daily (n ¼ 81). MMR rates by 12 months were higher in patients receiving radotinib 300 mg (52{\%}) or radotinib 400 mg twice-daily (46{\%}) versus imatinib (30{\%}; P ¼ 0.0044 and P ¼ 0.0342, respectively). Complete cytogenetic response (CCyR) rates by 12 months were higher for radotinib 300 mg (91{\%}) versus imatinib (77{\%}; P ¼ 0.0120). Early molecular response at 3 months occurred in 86{\%} and 87{\%} of patients receiving radotinib 300 mg and radotinib 400 mg, respectively, and 71{\%} of those receiving imatinib. By 12 months, no patients had progression to accelerated phase or blast crisis. Most adverse events were manageable with dose reduction. Conclusions: Radotinib demonstrated superiority over imatinib in CCyR and MMR in patients newly diagnosed with Philadelphia chromosome–positive CML-CP. This trial was registered at www.clinicaltrials.gov as NCT01511289.",
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T1 - Phase III clinical trial (RERISE study) results of efficacy and safety of radotinib compared with imatinib in newly diagnosed chronic phase chronic myeloid leukemia

AU - Kwak, Jae Yong

AU - Kim, Sung Hyun

AU - Oh, Suk Joong

AU - Zang, Dae Young

AU - Kim, Hawk

AU - Kim, Jeong A.

AU - Do, Young Rok

AU - Kim, Hyeoung Joon

AU - Park, Joon Seong

AU - Choi, Chul Won

AU - Lee, Won Sik

AU - Mun, Yeung Chul

AU - Kong, Jee Hyun

AU - Chung, Joo Seop

AU - Shin, Ho Jin

AU - Kim, Dae Young

AU - Park, Jinny

AU - Jung, Chul Won

AU - Bunworasate, Udomsak

AU - Comia, Narcisa Sonia

AU - Jootar, Saengsuree

AU - Reksodiputro, Arry Harryanto

AU - Caguioa, Priscilla B.

AU - Lee, Sung Eun

AU - Kim, Dong Wook

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Purpose: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for chronic phase chronic myeloid leukemia (CML-CP) in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP. Experimental Design: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily radotinib doses, or imatinib daily. The primary endpoint was major molecular response (MMR) by 12 months. Results: Two hundred forty-one patients were randomized to receive radotinib 300 mg (n ¼ 79) or 400 mg twice-daily (n ¼ 81), or imatinib 400 mg daily (n ¼ 81). MMR rates by 12 months were higher in patients receiving radotinib 300 mg (52%) or radotinib 400 mg twice-daily (46%) versus imatinib (30%; P ¼ 0.0044 and P ¼ 0.0342, respectively). Complete cytogenetic response (CCyR) rates by 12 months were higher for radotinib 300 mg (91%) versus imatinib (77%; P ¼ 0.0120). Early molecular response at 3 months occurred in 86% and 87% of patients receiving radotinib 300 mg and radotinib 400 mg, respectively, and 71% of those receiving imatinib. By 12 months, no patients had progression to accelerated phase or blast crisis. Most adverse events were manageable with dose reduction. Conclusions: Radotinib demonstrated superiority over imatinib in CCyR and MMR in patients newly diagnosed with Philadelphia chromosome–positive CML-CP. This trial was registered at www.clinicaltrials.gov as NCT01511289.

AB - Purpose: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for chronic phase chronic myeloid leukemia (CML-CP) in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP. Experimental Design: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily radotinib doses, or imatinib daily. The primary endpoint was major molecular response (MMR) by 12 months. Results: Two hundred forty-one patients were randomized to receive radotinib 300 mg (n ¼ 79) or 400 mg twice-daily (n ¼ 81), or imatinib 400 mg daily (n ¼ 81). MMR rates by 12 months were higher in patients receiving radotinib 300 mg (52%) or radotinib 400 mg twice-daily (46%) versus imatinib (30%; P ¼ 0.0044 and P ¼ 0.0342, respectively). Complete cytogenetic response (CCyR) rates by 12 months were higher for radotinib 300 mg (91%) versus imatinib (77%; P ¼ 0.0120). Early molecular response at 3 months occurred in 86% and 87% of patients receiving radotinib 300 mg and radotinib 400 mg, respectively, and 71% of those receiving imatinib. By 12 months, no patients had progression to accelerated phase or blast crisis. Most adverse events were manageable with dose reduction. Conclusions: Radotinib demonstrated superiority over imatinib in CCyR and MMR in patients newly diagnosed with Philadelphia chromosome–positive CML-CP. This trial was registered at www.clinicaltrials.gov as NCT01511289.

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