Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study
Abstract Background A prospective, randomised phase II study demonstrated clinical benefit of axitinib dose titration in a subset of treatment-naïve patients treated with axitinib for metastatic renal cell carcinoma. This analysis evaluated patient baseline characteristics that may impact overall su...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-01-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12885-018-5224-6 |
| _version_ | 1811200848537059328 |
|---|---|
| author | Yoshihiko Tomita Hirotsugu Uemura Mototsugu Oya Nobuo Shinohara Tomonori Habuchi Yosuke Fujii Yoichi Kamei Yoshiko Umeyama Angel H. Bair Brian I. Rini |
| author_facet | Yoshihiko Tomita Hirotsugu Uemura Mototsugu Oya Nobuo Shinohara Tomonori Habuchi Yosuke Fujii Yoichi Kamei Yoshiko Umeyama Angel H. Bair Brian I. Rini |
| author_sort | Yoshihiko Tomita |
| collection | DOAJ |
| description | Abstract Background A prospective, randomised phase II study demonstrated clinical benefit of axitinib dose titration in a subset of treatment-naïve patients treated with axitinib for metastatic renal cell carcinoma. This analysis evaluated patient baseline characteristics that may impact overall survival (OS) with axitinib dose titration. Methods Following a 4-week lead-in period during which all patients received axitinib 5 mg twice-daily (bid); patients meeting the predefined randomisation criteria were randomly assigned to receive axitinib 5 mg bid plus either axitinib or placebo titration. In exploratory analyses, patients were grouped into those who achieved OS ≥24 versus < 24 months, and compared their baseline characteristics with Fisher’s exact test or Cochran-Armitage trend exact test, with a 5% significance level. Potential predictive baseline characteristics associated with effect of axitinib dose titration on OS were investigated using a Cox proportional hazard model. Results Overall, 112 patients were randomised. Three of 56 patients receiving axitinib titration were censored; of the remaining 53, 33 (62%) achieved OS ≥24 months versus 20 (38%) with OS < 24 months. Patients with OS ≥24 vs. < 24 months, respectively, had significantly fewer metastatic sites (≤2 metastases: 52% vs. 10%; ≥3 metastases: 48% vs. 90%), fewer lymph node (45% vs. 75%) or liver (15% vs. 45%) metastases, higher haemoglobin level (i.e., ≥ lower limit of normal: 67% vs. 25%) at baseline, lower neutrophil (≤ upper limit of normal, 97% vs. 75%) and platelet (≤ upper limit of normal, 82% vs. 50%) levels at baseline and ≥ 1 year between histopathological diagnosis and treatment (64% vs. 15%). The primary reason for treatment discontinuation in both OS groups was disease progression. The frequency of toxicity-related discontinuation was comparable between the 2 groups, indicating that it was not a factor for a shorter OS. The multivariate analysis showed that ≥1 year from histopathological diagnosis to treatment and baseline haemoglobin level equal or greater than lower limit of normal were significant covariates associated with favourable OS in patients receiving axitinib titration. Conclusions The current analyses identified potentially predictive factors that could help selecting patients who may benefit from axitinib dose titration. Trial registration ClinicalTrials.gov identifier, NCT00835978. Registered prospectively, February 4, 2009. |
| first_indexed | 2024-04-12T02:10:40Z |
| format | Article |
| id | doaj.art-e3c513bc63be438997c0bbcecb38ef8c |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-12T02:10:40Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-e3c513bc63be438997c0bbcecb38ef8c2022-12-22T03:52:24ZengBMCBMC Cancer1471-24072019-01-0119111110.1186/s12885-018-5224-6Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II studyYoshihiko Tomita0Hirotsugu Uemura1Mototsugu Oya2Nobuo Shinohara3Tomonori Habuchi4Yosuke Fujii5Yoichi Kamei6Yoshiko Umeyama7Angel H. Bair8Brian I. Rini9Department of Urology, Department of Molecular Oncology, Niigata University Graduate School of Medical and Dental SciencesDepartment of Urology, Kindai University Faculty of MedicineDepartment of Urology, Keio University School of MedicineDepartment of Urology, Hokkaido University Graduate School of MedicineDepartment of Urology, Akita University School of MedicinePfizer Japan IncPfizer Japan IncPfizer Japan IncPfizer OncologyDepartment of Solid Tumour Oncology, Cleveland Clinic Taussig Cancer InstituteAbstract Background A prospective, randomised phase II study demonstrated clinical benefit of axitinib dose titration in a subset of treatment-naïve patients treated with axitinib for metastatic renal cell carcinoma. This analysis evaluated patient baseline characteristics that may impact overall survival (OS) with axitinib dose titration. Methods Following a 4-week lead-in period during which all patients received axitinib 5 mg twice-daily (bid); patients meeting the predefined randomisation criteria were randomly assigned to receive axitinib 5 mg bid plus either axitinib or placebo titration. In exploratory analyses, patients were grouped into those who achieved OS ≥24 versus < 24 months, and compared their baseline characteristics with Fisher’s exact test or Cochran-Armitage trend exact test, with a 5% significance level. Potential predictive baseline characteristics associated with effect of axitinib dose titration on OS were investigated using a Cox proportional hazard model. Results Overall, 112 patients were randomised. Three of 56 patients receiving axitinib titration were censored; of the remaining 53, 33 (62%) achieved OS ≥24 months versus 20 (38%) with OS < 24 months. Patients with OS ≥24 vs. < 24 months, respectively, had significantly fewer metastatic sites (≤2 metastases: 52% vs. 10%; ≥3 metastases: 48% vs. 90%), fewer lymph node (45% vs. 75%) or liver (15% vs. 45%) metastases, higher haemoglobin level (i.e., ≥ lower limit of normal: 67% vs. 25%) at baseline, lower neutrophil (≤ upper limit of normal, 97% vs. 75%) and platelet (≤ upper limit of normal, 82% vs. 50%) levels at baseline and ≥ 1 year between histopathological diagnosis and treatment (64% vs. 15%). The primary reason for treatment discontinuation in both OS groups was disease progression. The frequency of toxicity-related discontinuation was comparable between the 2 groups, indicating that it was not a factor for a shorter OS. The multivariate analysis showed that ≥1 year from histopathological diagnosis to treatment and baseline haemoglobin level equal or greater than lower limit of normal were significant covariates associated with favourable OS in patients receiving axitinib titration. Conclusions The current analyses identified potentially predictive factors that could help selecting patients who may benefit from axitinib dose titration. Trial registration ClinicalTrials.gov identifier, NCT00835978. Registered prospectively, February 4, 2009.http://link.springer.com/article/10.1186/s12885-018-5224-6AxitinibBenefit with dose titrationFirst-lineMetastatic renal cell carcinomaPredictive factorsSurvival benefit |
| spellingShingle | Yoshihiko Tomita Hirotsugu Uemura Mototsugu Oya Nobuo Shinohara Tomonori Habuchi Yosuke Fujii Yoichi Kamei Yoshiko Umeyama Angel H. Bair Brian I. Rini Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study BMC Cancer Axitinib Benefit with dose titration First-line Metastatic renal cell carcinoma Predictive factors Survival benefit |
| title | Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study |
| title_full | Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study |
| title_fullStr | Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study |
| title_full_unstemmed | Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study |
| title_short | Patients with metastatic renal cell carcinoma who benefit from axitinib dose titration: analysis from a randomised, double-blind phase II study |
| title_sort | patients with metastatic renal cell carcinoma who benefit from axitinib dose titration analysis from a randomised double blind phase ii study |
| topic | Axitinib Benefit with dose titration First-line Metastatic renal cell carcinoma Predictive factors Survival benefit |
| url | http://link.springer.com/article/10.1186/s12885-018-5224-6 |
| work_keys_str_mv | AT yoshihikotomita patientswithmetastaticrenalcellcarcinomawhobenefitfromaxitinibdosetitrationanalysisfromarandomiseddoubleblindphaseiistudy AT hirotsuguuemura patientswithmetastaticrenalcellcarcinomawhobenefitfromaxitinibdosetitrationanalysisfromarandomiseddoubleblindphaseiistudy AT mototsuguoya patientswithmetastaticrenalcellcarcinomawhobenefitfromaxitinibdosetitrationanalysisfromarandomiseddoubleblindphaseiistudy AT nobuoshinohara patientswithmetastaticrenalcellcarcinomawhobenefitfromaxitinibdosetitrationanalysisfromarandomiseddoubleblindphaseiistudy AT tomonorihabuchi patientswithmetastaticrenalcellcarcinomawhobenefitfromaxitinibdosetitrationanalysisfromarandomiseddoubleblindphaseiistudy AT yosukefujii patientswithmetastaticrenalcellcarcinomawhobenefitfromaxitinibdosetitrationanalysisfromarandomiseddoubleblindphaseiistudy AT yoichikamei patientswithmetastaticrenalcellcarcinomawhobenefitfromaxitinibdosetitrationanalysisfromarandomiseddoubleblindphaseiistudy AT yoshikoumeyama patientswithmetastaticrenalcellcarcinomawhobenefitfromaxitinibdosetitrationanalysisfromarandomiseddoubleblindphaseiistudy AT angelhbair patientswithmetastaticrenalcellcarcinomawhobenefitfromaxitinibdosetitrationanalysisfromarandomiseddoubleblindphaseiistudy AT brianirini patientswithmetastaticrenalcellcarcinomawhobenefitfromaxitinibdosetitrationanalysisfromarandomiseddoubleblindphaseiistudy |