A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: ENESTKorea
Abstract Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML‐CP). We investigated the 2‐year efficacy and safety of nilotinib and their rel...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2018-05-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.1450 |
| _version_ | 1811154927724003328 |
|---|---|
| author | Junghoon Shin Youngil Koh Seo Hyun Yoon Joo‐Youn Cho Dae‐Young Kim Kyoo‐Hyung Lee Hyeong‐Joon Kim Jae‐Sook Ahn Yeo‐Kyeoung Kim Jinny Park Sang‐Kyun Sohn Joon Ho Moon Yoo Jin Lee Seonghae Yoon Jeong‐Ok Lee June‐Won Cheong Kyoung Ha Kim Sung‐Hyun Kim Hoon‐Gu Kim Hawk Kim Seung‐Hyun Nam Young Rok Do Sang‐Gon Park Seong Kyu Park Sung Hwa Bae Hun Ho Song Dong‐Yeop Shin Doyeun Oh Min Kyoung Kim Chul Won Jung Seonyang Park Inho Kim |
| author_facet | Junghoon Shin Youngil Koh Seo Hyun Yoon Joo‐Youn Cho Dae‐Young Kim Kyoo‐Hyung Lee Hyeong‐Joon Kim Jae‐Sook Ahn Yeo‐Kyeoung Kim Jinny Park Sang‐Kyun Sohn Joon Ho Moon Yoo Jin Lee Seonghae Yoon Jeong‐Ok Lee June‐Won Cheong Kyoung Ha Kim Sung‐Hyun Kim Hoon‐Gu Kim Hawk Kim Seung‐Hyun Nam Young Rok Do Sang‐Gon Park Seong Kyu Park Sung Hwa Bae Hun Ho Song Dong‐Yeop Shin Doyeun Oh Min Kyoung Kim Chul Won Jung Seonyang Park Inho Kim |
| author_sort | Junghoon Shin |
| collection | DOAJ |
| description | Abstract Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML‐CP). We investigated the 2‐year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNCs). In this open‐label, multi‐institutional phase 4 study, 110 Philadelphia chromosome‐positive CML‐CP patients were treated with nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and AEs were monitored for up to 24 months. The 24‐month cumulative MR4.5 rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNCs, and the per‐patient mean was used to categorize them into four mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between groups. With a median follow‐up of 22.2 months, the 24‐month cumulative MR4.5 rate was 56.2% (95% confidence interval, 44.0%–8.3%), and the median time to MR4.5 was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR4, and MR4.5 between MPNC groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC groups, there was no significant linear trend in the frequency of AEs. Nilotinib is highly effective for the treatment of CML‐CP with manageable AEs. The measurement of PNC has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT03332511. |
| first_indexed | 2024-04-10T04:25:30Z |
| format | Article |
| id | doaj.art-d3afcb08b0d94b2f8771feee46de40c7 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-10T04:25:30Z |
| publishDate | 2018-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-d3afcb08b0d94b2f8771feee46de40c72023-03-10T15:42:21ZengWileyCancer Medicine2045-76342018-05-01751814182310.1002/cam4.1450A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: ENESTKoreaJunghoon Shin0Youngil Koh1Seo Hyun Yoon2Joo‐Youn Cho3Dae‐Young Kim4Kyoo‐Hyung Lee5Hyeong‐Joon Kim6Jae‐Sook Ahn7Yeo‐Kyeoung Kim8Jinny Park9Sang‐Kyun Sohn10Joon Ho Moon11Yoo Jin Lee12Seonghae Yoon13Jeong‐Ok Lee14June‐Won Cheong15Kyoung Ha Kim16Sung‐Hyun Kim17Hoon‐Gu Kim18Hawk Kim19Seung‐Hyun Nam20Young Rok Do21Sang‐Gon Park22Seong Kyu Park23Sung Hwa Bae24Hun Ho Song25Dong‐Yeop Shin26Doyeun Oh27Min Kyoung Kim28Chul Won Jung29Seonyang Park30Inho Kim31Department of Internal Medicine Seoul National University Hospital Cancer Research Institute Seoul National University College of Medicine Seoul KoreaDepartment of Internal Medicine Seoul National University Hospital Cancer Research Institute Seoul National University College of Medicine Seoul KoreaDepartment of Clinical Pharmacology and Therapeutics Seoul National University Hospital Seoul KoreaDepartment of Clinical Pharmacology and Therapeutics Seoul National University Hospital Seoul KoreaDepartment of Internal Medicine Asan Medical Center Seoul KoreaDepartment of Internal Medicine Asan Medical Center Seoul KoreaDepartment of Internal Medicine Chonnam National University Hwasun Hospital Hwasun KoreaDepartment of Internal Medicine Chonnam National University Hwasun Hospital Hwasun KoreaDepartment of Internal Medicine Chonnam National University Hwasun Hospital Hwasun KoreaDepartment of Internal Medicine Gachon University Gil Medical Center Incheon KoreaDepartment of Internal Medicine Kyungpook National University Hospital Daegu KoreaDepartment of Internal Medicine Kyungpook National University Hospital Daegu KoreaDepartment of Internal Medicine Kyungpook National University Hospital Daegu KoreaClinical Trials Center Seoul National University Bundang Hospital Seongnam KoreaDepartment of Internal Medicine Seoul National University Bundang Hospital Seongnam KoreaDepartment of Internal Medicine Severance Hospital Seoul KoreaDepartment of Internal Medicine Soonchunhyang University Seoul Hospital Seoul KoreaDepartment of Internal Medicine Dong‐A University Hospital Busan KoreaDepartment of Internal Medicine Gyeongsang National University Hospital Jinju KoreaDepartment of Internal Medicine Ulsan University Hospital Ulsan KoreaDepartment of Internal Medicine VHS Medical Center Seoul KoreaDepartment of Internal Medicine Keimyung University Dongsan Medical Center Daegu KoreaDepartment of Internal Medicine Chosun University Hospital Gwangju KoreaDepartment of Internal Medicine Soonchunhyang University Bucheon Hospital Bucheon KoreaDepartment of Internal Medicine Daegu Catholic University Medical Center Daegu KoreaDepartment of Internal Medicine Kangdong Sacred Heart Hospital Seoul KoreaDepartment of Internal Medicine Korea Cancer Center Hospital Seoul KoreaDepartment of Internal Medicine CHA Bundang Medical Center Seongnam KoreaDepartment of Internal Medicine Yeungnam University Medical Center Daegu KoreaDepartment of Internal Medicine Samsung Medical Center Seoul KoreaDepartment of Internal Medicine Seoul National University Hospital Cancer Research Institute Seoul National University College of Medicine Seoul KoreaDepartment of Internal Medicine Seoul National University Hospital Cancer Research Institute Seoul National University College of Medicine Seoul KoreaAbstract Although nilotinib has improved efficacy compared to imatinib, suboptimal response and intolerable adverse events (AEs) limit its effectiveness in many patients with chronic myeloid leukemia in chronic phase (CML‐CP). We investigated the 2‐year efficacy and safety of nilotinib and their relationships with plasma nilotinib concentrations (PNCs). In this open‐label, multi‐institutional phase 4 study, 110 Philadelphia chromosome‐positive CML‐CP patients were treated with nilotinib at a starting dose of 300 mg twice daily. Molecular responses (MRs) and AEs were monitored for up to 24 months. The 24‐month cumulative MR4.5 rate was evaluated as the primary endpoint. Plasma samples were collected from 94 patients to determine PNCs, and the per‐patient mean was used to categorize them into four mean PNC (MPNC) groups. Cumulative MR rates and safety were compared between groups. With a median follow‐up of 22.2 months, the 24‐month cumulative MR4.5 rate was 56.2% (95% confidence interval, 44.0%–8.3%), and the median time to MR4.5 was 23.3 months. There were no significant differences in the cumulative rates of major molecular response, MR4, and MR4.5 between MPNC groups. One patient died due to acute viral hepatitis, and two developed hematological or cytogenetic relapse, while no progression to accelerated or blast phase was observed. Safety results were consistent with previous studies with no new safety signal identified. Across the MPNC groups, there was no significant linear trend in the frequency of AEs. Nilotinib is highly effective for the treatment of CML‐CP with manageable AEs. The measurement of PNC has no predictive value for patient outcomes and is thus not found to be clinically useful. This study is registered with clinicaltrials.gov, Number NCT03332511.https://doi.org/10.1002/cam4.1450CMLmolecular responsenilotinibprognosis |
| spellingShingle | Junghoon Shin Youngil Koh Seo Hyun Yoon Joo‐Youn Cho Dae‐Young Kim Kyoo‐Hyung Lee Hyeong‐Joon Kim Jae‐Sook Ahn Yeo‐Kyeoung Kim Jinny Park Sang‐Kyun Sohn Joon Ho Moon Yoo Jin Lee Seonghae Yoon Jeong‐Ok Lee June‐Won Cheong Kyoung Ha Kim Sung‐Hyun Kim Hoon‐Gu Kim Hawk Kim Seung‐Hyun Nam Young Rok Do Sang‐Gon Park Seong Kyu Park Sung Hwa Bae Hun Ho Song Dong‐Yeop Shin Doyeun Oh Min Kyoung Kim Chul Won Jung Seonyang Park Inho Kim A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: ENESTKorea Cancer Medicine CML molecular response nilotinib prognosis |
| title | A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: ENESTKorea |
| title_full | A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: ENESTKorea |
| title_fullStr | A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: ENESTKorea |
| title_full_unstemmed | A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: ENESTKorea |
| title_short | A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome‐positive chronic myeloid leukemia in chronic phase: ENESTKorea |
| title_sort | phase 4 study of nilotinib in korean patients with philadelphia chromosome positive chronic myeloid leukemia in chronic phase enestkorea |
| topic | CML molecular response nilotinib prognosis |
| url | https://doi.org/10.1002/cam4.1450 |
| work_keys_str_mv | AT junghoonshin aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT youngilkoh aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT seohyunyoon aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT jooyouncho aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT daeyoungkim aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT kyoohyunglee aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT hyeongjoonkim aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT jaesookahn aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT yeokyeoungkim aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT jinnypark aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT sangkyunsohn aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT joonhomoon aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT yoojinlee aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT seonghaeyoon aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT jeongoklee aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT junewoncheong aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT kyounghakim aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT sunghyunkim aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT hoongukim aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT hawkkim aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT seunghyunnam aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT youngrokdo aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT sanggonpark aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT seongkyupark aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT sunghwabae aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT hunhosong aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT dongyeopshin aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT doyeunoh aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT minkyoungkim aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT chulwonjung aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT seonyangpark aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT inhokim aphase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT junghoonshin phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT youngilkoh phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT seohyunyoon phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT jooyouncho phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT daeyoungkim phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT kyoohyunglee phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT hyeongjoonkim phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT jaesookahn phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT yeokyeoungkim phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT jinnypark phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT sangkyunsohn phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT joonhomoon phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT yoojinlee phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT seonghaeyoon phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT jeongoklee phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT junewoncheong phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT kyounghakim phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT sunghyunkim phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT hoongukim phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT hawkkim phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT seunghyunnam phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT youngrokdo phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT sanggonpark phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT seongkyupark phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT sunghwabae phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT hunhosong phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT dongyeopshin phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT doyeunoh phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT minkyoungkim phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT chulwonjung phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT seonyangpark phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea AT inhokim phase4studyofnilotinibinkoreanpatientswithphiladelphiachromosomepositivechronicmyeloidleukemiainchronicphaseenestkorea |