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 Comia; Saengsuree Jootar; Arry Harryanto Reksodiputro; Priscilla B. Caguioa; Sung Eun Lee; Dong Wook Kim

doi:10.1158/1078-0432.CCR-17-0957

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

Research output: Contribution to journal › Article › peer-review

49 Citations (Scopus)

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 language	English
Pages (from-to)	7180-7188
Number of pages	9
Journal	Clinical Cancer Research
Volume	23
Issue number	23
DOIs	https://doi.org/10.1158/1078-0432.CCR-17-0957
Publication status	Published - 2017 Dec 1
Externally published	Yes

Bibliographical note

Funding Information:
S-H. Kim reports receiving speakers bureau honoraria from Dae-Woong Pharmaceutic Company. Y.R. Do reports receiving speakers bureau honoraria and reports receiving commercial research grants from Bristol-Myers Squibb and Novartis. C.W. Choi reports receiving commercial research grants from Il-Yang Pharm. D-Y. Kim reports receiving commercial research grants from Ilyang Co. and Roche. A.H. Reksodiputro reports receiving commercial research grants from Il-Yang Pharm. D-W. Kim reports receiving speakers bureau honoraria from Ilyang Co. and Novartis, is a consultant/advisory board member for Bristol-Myers Squibb, Ilyang Co., Novartis and Pfizer, and reports receiving commercial research grants from Ariad Co., Ilyang Co., Novartis and Pfizer. No potential conflicts of interest were disclosed by the other authors. Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): J.-Y. Kwak, S.-H. Kim, S.J. Oh, D.Y. Zang, H. Kim, J.-A. Kim, Y.R. Do, H.J. Kim, J.S. Park, C.W. Choi, W.S. Lee, Y.-C. Mun, J.S. Chung, H.-J. Shin, D.-Y. Kim, J. Park, C.W. Jung, U. Bunworasate, N.S. Comia, S. Jootar, P.B. Caguioa, S.-E. Lee, D.-W. Kim Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): J.-Y. Kwak, D.-Y. Kim, C.W. Jung, S.-E. Lee, D.-W. Kim Writing, review, and/or revision of the manuscript: J.-Y. Kwak, S.-H. Kim, D.Y. Zang, J.-A. Kim, Y.R. Do, C.W. Choi, W.S. Lee, Y.-C. Mun, J.H. Kong, J.S. Chung, D.-Y. Kim, J. Park, C.W. Jung, A.H. Reksodiputro, D.-W. Kim Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): S. Jootar, A.H. Reksodiputro, D.-W. Kim Study supervision: A.H. Reksodiputro, D.-W. Kim We thank the patients and investigators for their participation in the trial and the Korea Leukemia Bank for biomaterial banking and analysis (NRF-2013M3A9B8031236). This study was funded by IL-YANG Pharmaceutical Co., Ltd, which also funded medical writing assistance. Professional medical writing and editorial assistance were provided by Lauren Gallagher, PhD, and Emilia Raszkiewicz of StemScientific, an Ashfield company, with funding from IL-YANG Pharmaceutical Co., Ltd. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Publisher Copyright:
©2017 AACR.

ASJC Scopus subject areas

Medicine(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1158/1078-0432.CCR-17-0957

Cite this

Kwak, J. Y., Kim, S. H., Oh, S. J., Zang, D. Y., Kim, H., Kim, J. A., Do, Y. R., Kim, H. J., Park, J. S., Choi, C. W., Lee, W. S., Mun, Y. C., Kong, J. H., Chung, J. S., Shin, H. J., Kim, D. Y., Park, J., Jung, C. W., Bunworasate, U., ... Kim, D. W. (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, 23(23), 7180-7188. https://doi.org/10.1158/1078-0432.CCR-17-0957

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

@article{a467d79aaba84a7991da6cf52593d4e7,

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

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.",

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

note = "Funding Information: S-H. Kim reports receiving speakers bureau honoraria from Dae-Woong Pharmaceutic Company. Y.R. Do reports receiving speakers bureau honoraria and reports receiving commercial research grants from Bristol-Myers Squibb and Novartis. C.W. Choi reports receiving commercial research grants from Il-Yang Pharm. D-Y. Kim reports receiving commercial research grants from Ilyang Co. and Roche. A.H. Reksodiputro reports receiving commercial research grants from Il-Yang Pharm. D-W. Kim reports receiving speakers bureau honoraria from Ilyang Co. and Novartis, is a consultant/advisory board member for Bristol-Myers Squibb, Ilyang Co., Novartis and Pfizer, and reports receiving commercial research grants from Ariad Co., Ilyang Co., Novartis and Pfizer. No potential conflicts of interest were disclosed by the other authors. Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): J.-Y. Kwak, S.-H. Kim, S.J. Oh, D.Y. Zang, H. Kim, J.-A. Kim, Y.R. Do, H.J. Kim, J.S. Park, C.W. Choi, W.S. Lee, Y.-C. Mun, J.S. Chung, H.-J. Shin, D.-Y. Kim, J. Park, C.W. Jung, U. Bunworasate, N.S. Comia, S. Jootar, P.B. Caguioa, S.-E. Lee, D.-W. Kim Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): J.-Y. Kwak, D.-Y. Kim, C.W. Jung, S.-E. Lee, D.-W. Kim Writing, review, and/or revision of the manuscript: J.-Y. Kwak, S.-H. Kim, D.Y. Zang, J.-A. Kim, Y.R. Do, C.W. Choi, W.S. Lee, Y.-C. Mun, J.H. Kong, J.S. Chung, D.-Y. Kim, J. Park, C.W. Jung, A.H. Reksodiputro, D.-W. Kim Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): S. Jootar, A.H. Reksodiputro, D.-W. Kim Study supervision: A.H. Reksodiputro, D.-W. Kim We thank the patients and investigators for their participation in the trial and the Korea Leukemia Bank for biomaterial banking and analysis (NRF-2013M3A9B8031236). This study was funded by IL-YANG Pharmaceutical Co., Ltd, which also funded medical writing assistance. Professional medical writing and editorial assistance were provided by Lauren Gallagher, PhD, and Emilia Raszkiewicz of StemScientific, an Ashfield company, with funding from IL-YANG Pharmaceutical Co., Ltd. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Publisher Copyright: {\textcopyright}2017 AACR.",

year = "2017",

month = dec,

day = "1",

doi = "10.1158/1078-0432.CCR-17-0957",

language = "English",

volume = "23",

pages = "7180--7188",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "23",

}

TY - JOUR

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

N1 - Funding Information: S-H. Kim reports receiving speakers bureau honoraria from Dae-Woong Pharmaceutic Company. Y.R. Do reports receiving speakers bureau honoraria and reports receiving commercial research grants from Bristol-Myers Squibb and Novartis. C.W. Choi reports receiving commercial research grants from Il-Yang Pharm. D-Y. Kim reports receiving commercial research grants from Ilyang Co. and Roche. A.H. Reksodiputro reports receiving commercial research grants from Il-Yang Pharm. D-W. Kim reports receiving speakers bureau honoraria from Ilyang Co. and Novartis, is a consultant/advisory board member for Bristol-Myers Squibb, Ilyang Co., Novartis and Pfizer, and reports receiving commercial research grants from Ariad Co., Ilyang Co., Novartis and Pfizer. No potential conflicts of interest were disclosed by the other authors. Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): J.-Y. Kwak, S.-H. Kim, S.J. Oh, D.Y. Zang, H. Kim, J.-A. Kim, Y.R. Do, H.J. Kim, J.S. Park, C.W. Choi, W.S. Lee, Y.-C. Mun, J.S. Chung, H.-J. Shin, D.-Y. Kim, J. Park, C.W. Jung, U. Bunworasate, N.S. Comia, S. Jootar, P.B. Caguioa, S.-E. Lee, D.-W. Kim Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): J.-Y. Kwak, D.-Y. Kim, C.W. Jung, S.-E. Lee, D.-W. Kim Writing, review, and/or revision of the manuscript: J.-Y. Kwak, S.-H. Kim, D.Y. Zang, J.-A. Kim, Y.R. Do, C.W. Choi, W.S. Lee, Y.-C. Mun, J.H. Kong, J.S. Chung, D.-Y. Kim, J. Park, C.W. Jung, A.H. Reksodiputro, D.-W. Kim Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): S. Jootar, A.H. Reksodiputro, D.-W. Kim Study supervision: A.H. Reksodiputro, D.-W. Kim We thank the patients and investigators for their participation in the trial and the Korea Leukemia Bank for biomaterial banking and analysis (NRF-2013M3A9B8031236). This study was funded by IL-YANG Pharmaceutical Co., Ltd, which also funded medical writing assistance. Professional medical writing and editorial assistance were provided by Lauren Gallagher, PhD, and Emilia Raszkiewicz of StemScientific, an Ashfield company, with funding from IL-YANG Pharmaceutical Co., Ltd. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Publisher Copyright: ©2017 AACR.

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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U2 - 10.1158/1078-0432.CCR-17-0957

DO - 10.1158/1078-0432.CCR-17-0957

M3 - Article

C2 - 28939746

AN - SCOPUS:85037616835

SN - 1078-0432

VL - 23

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EP - 7188

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 23

ER -

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

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