Key predictive factors for efficacy of axitinib in first-line metastatic renal cell carcinoma: Subgroup analysis in Japanese patients from a randomized, double-blind phase II study

Yoshihiko Tomita, Satoshi Fukasawa, Mototsugu Oya, Hirotsugu Uemura, Nobuo Shinohara, Tomonori Habuchi, Brian I. Rini, Ying Chen, Angel H. Bair, Seiichiro Ozono, Seiji Naito, Hideyuki Akaza

Research output: Contribution to journalArticle

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Abstract

Objectives: To conduct Japanese subgroup analyses of a randomized, global Phase II study of axitinib with and without dose titration in first-line metastatic renal cell carcinoma and to explore predictive factors for axitinib efficacy in first-line metastatic renal cell carcinoma. Methods: The data included 44 Japanese and 169 non-Japanese treatment-naïve patients with metastatic renal cell carcinoma. Patients received twice-daily axitinib 5mg during a 4-week lead-in period. Patients who met the pre-defined randomization criteria were stratified by Eastern Cooperative Oncology Group performance status and randomly assigned (1:1) to axitinib or placebo titration. The primary endpoint was objective response rate; secondary endpoints included progression-free survival and safety. Predictive factors were analyzed using data from all patients. Results: The objective response rate (95% confidence interval) was 66% (50-80%) vs. 44% (36- 52%) in Japanese and non-Japanese patients, respectively. At the primary analysis, median progression-free survival could not be estimated for Japanese patients, and was 27.6 months (95% confidence interval: 16.6-33.2) in an updated analysis. Hypertension, diarrhea, hand-foot syndrome, dysphonia, hypothyroidism and proteinuria were common adverse events in Japanese patients. Due to a small number of randomized patients, effects of axitinib dose titration could not sufficiently be confirmed among Japanese patients. The multivariate analysis identified time from histopathological diagnosis to treatment and sum of the longest diameter for target lesion at baseline as independent predictive factors for progression-free survival. Conclusions: Axitinib is effective and well tolerated as first-line metastatic renal cell carcinoma therapy in Japanese patients. Predictive factors for axitinib efficacy endpoints identified in this setting warrant further investigation.

Original languageEnglish
Pages (from-to)1031-1041
Number of pages11
JournalJapanese Journal of Clinical Oncology
Volume46
Issue number11
DOIs
Publication statusPublished - 2016

Fingerprint

Renal Cell Carcinoma
Disease-Free Survival
axitinib
Hand-Foot Syndrome
Confidence Intervals
Dysphonia
Random Allocation
Cell- and Tissue-Based Therapy
Hypothyroidism
Proteinuria
Diarrhea
Multivariate Analysis
Placebos
Hypertension
Safety
Therapeutics

Keywords

  • Axitinib
  • Japanese
  • Molecular targeted therapy
  • Randomized clinical trial
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Key predictive factors for efficacy of axitinib in first-line metastatic renal cell carcinoma : Subgroup analysis in Japanese patients from a randomized, double-blind phase II study. / Tomita, Yoshihiko; Fukasawa, Satoshi; Oya, Mototsugu; Uemura, Hirotsugu; Shinohara, Nobuo; Habuchi, Tomonori; Rini, Brian I.; Chen, Ying; Bair, Angel H.; Ozono, Seiichiro; Naito, Seiji; Akaza, Hideyuki.

In: Japanese Journal of Clinical Oncology, Vol. 46, No. 11, 2016, p. 1031-1041.

Research output: Contribution to journalArticle

Tomita, Yoshihiko ; Fukasawa, Satoshi ; Oya, Mototsugu ; Uemura, Hirotsugu ; Shinohara, Nobuo ; Habuchi, Tomonori ; Rini, Brian I. ; Chen, Ying ; Bair, Angel H. ; Ozono, Seiichiro ; Naito, Seiji ; Akaza, Hideyuki. / Key predictive factors for efficacy of axitinib in first-line metastatic renal cell carcinoma : Subgroup analysis in Japanese patients from a randomized, double-blind phase II study. In: Japanese Journal of Clinical Oncology. 2016 ; Vol. 46, No. 11. pp. 1031-1041.
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author = "Yoshihiko Tomita and Satoshi Fukasawa and Mototsugu Oya and Hirotsugu Uemura and Nobuo Shinohara and Tomonori Habuchi and Rini, {Brian I.} and Ying Chen and Bair, {Angel H.} and Seiichiro Ozono and Seiji Naito and Hideyuki Akaza",
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T1 - Key predictive factors for efficacy of axitinib in first-line metastatic renal cell carcinoma

T2 - Subgroup analysis in Japanese patients from a randomized, double-blind phase II study

AU - Tomita, Yoshihiko

AU - Fukasawa, Satoshi

AU - Oya, Mototsugu

AU - Uemura, Hirotsugu

AU - Shinohara, Nobuo

AU - Habuchi, Tomonori

AU - Rini, Brian I.

AU - Chen, Ying

AU - Bair, Angel H.

AU - Ozono, Seiichiro

AU - Naito, Seiji

AU - Akaza, Hideyuki

PY - 2016

Y1 - 2016

N2 - Objectives: To conduct Japanese subgroup analyses of a randomized, global Phase II study of axitinib with and without dose titration in first-line metastatic renal cell carcinoma and to explore predictive factors for axitinib efficacy in first-line metastatic renal cell carcinoma. Methods: The data included 44 Japanese and 169 non-Japanese treatment-naïve patients with metastatic renal cell carcinoma. Patients received twice-daily axitinib 5mg during a 4-week lead-in period. Patients who met the pre-defined randomization criteria were stratified by Eastern Cooperative Oncology Group performance status and randomly assigned (1:1) to axitinib or placebo titration. The primary endpoint was objective response rate; secondary endpoints included progression-free survival and safety. Predictive factors were analyzed using data from all patients. Results: The objective response rate (95% confidence interval) was 66% (50-80%) vs. 44% (36- 52%) in Japanese and non-Japanese patients, respectively. At the primary analysis, median progression-free survival could not be estimated for Japanese patients, and was 27.6 months (95% confidence interval: 16.6-33.2) in an updated analysis. Hypertension, diarrhea, hand-foot syndrome, dysphonia, hypothyroidism and proteinuria were common adverse events in Japanese patients. Due to a small number of randomized patients, effects of axitinib dose titration could not sufficiently be confirmed among Japanese patients. The multivariate analysis identified time from histopathological diagnosis to treatment and sum of the longest diameter for target lesion at baseline as independent predictive factors for progression-free survival. Conclusions: Axitinib is effective and well tolerated as first-line metastatic renal cell carcinoma therapy in Japanese patients. Predictive factors for axitinib efficacy endpoints identified in this setting warrant further investigation.

AB - Objectives: To conduct Japanese subgroup analyses of a randomized, global Phase II study of axitinib with and without dose titration in first-line metastatic renal cell carcinoma and to explore predictive factors for axitinib efficacy in first-line metastatic renal cell carcinoma. Methods: The data included 44 Japanese and 169 non-Japanese treatment-naïve patients with metastatic renal cell carcinoma. Patients received twice-daily axitinib 5mg during a 4-week lead-in period. Patients who met the pre-defined randomization criteria were stratified by Eastern Cooperative Oncology Group performance status and randomly assigned (1:1) to axitinib or placebo titration. The primary endpoint was objective response rate; secondary endpoints included progression-free survival and safety. Predictive factors were analyzed using data from all patients. Results: The objective response rate (95% confidence interval) was 66% (50-80%) vs. 44% (36- 52%) in Japanese and non-Japanese patients, respectively. At the primary analysis, median progression-free survival could not be estimated for Japanese patients, and was 27.6 months (95% confidence interval: 16.6-33.2) in an updated analysis. Hypertension, diarrhea, hand-foot syndrome, dysphonia, hypothyroidism and proteinuria were common adverse events in Japanese patients. Due to a small number of randomized patients, effects of axitinib dose titration could not sufficiently be confirmed among Japanese patients. The multivariate analysis identified time from histopathological diagnosis to treatment and sum of the longest diameter for target lesion at baseline as independent predictive factors for progression-free survival. Conclusions: Axitinib is effective and well tolerated as first-line metastatic renal cell carcinoma therapy in Japanese patients. Predictive factors for axitinib efficacy endpoints identified in this setting warrant further investigation.

KW - Axitinib

KW - Japanese

KW - Molecular targeted therapy

KW - Randomized clinical trial

KW - Renal cell carcinoma

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