Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma

Results from the phase III, randomized ATLAS trial

M. Gross-Goupil, T. G. Kwon, Masatoshi Eto, D. Ye, H. Miyake, S. I. Seo, S. S. Byun, J. L. Lee, V. Master, J. Jin, R. DeBenedetto, R. Linke, M. Casey, B. Rosbrook, M. Lechuga, O. Valota, E. Grande, D. I. Quinn

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Abstract

Background: The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methods: In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [pT2 and/or Nþ, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1: 1) oral twice-daily axitinib 5 mg or placebo for 3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG 3 or pT4 and/or Nþ, any T, any FG) was conducted. Results: A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) ¼ 0.870; 95% confidence interval (CI): 0.660-1.147; P ¼ 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468-0.879; P ¼ 0.0051), and by IRC (0.735; 0.525-1.028; P ¼ 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo. Conclusions: ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration number: NCT01599754.

Original languageEnglish
Pages (from-to)2371-2378
Number of pages8
JournalAnnals of Oncology
Volume29
Issue number12
DOIs
Publication statusPublished - Jan 1 2018

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Renal Cell Carcinoma
Disease-Free Survival
Placebos
Advisory Committees
Nephrectomy
Therapeutics
Research Personnel
Confidence Intervals
Medical Futility
Recurrence
Second Primary Neoplasms
Risk Reduction Behavior
Survival Analysis
axitinib
Safety
Survival
Population

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma : Results from the phase III, randomized ATLAS trial. / Gross-Goupil, M.; Kwon, T. G.; Eto, Masatoshi; Ye, D.; Miyake, H.; Seo, S. I.; Byun, S. S.; Lee, J. L.; Master, V.; Jin, J.; DeBenedetto, R.; Linke, R.; Casey, M.; Rosbrook, B.; Lechuga, M.; Valota, O.; Grande, E.; Quinn, D. I.

In: Annals of Oncology, Vol. 29, No. 12, 01.01.2018, p. 2371-2378.

Research output: Contribution to journalArticle

Gross-Goupil, M, Kwon, TG, Eto, M, Ye, D, Miyake, H, Seo, SI, Byun, SS, Lee, JL, Master, V, Jin, J, DeBenedetto, R, Linke, R, Casey, M, Rosbrook, B, Lechuga, M, Valota, O, Grande, E & Quinn, DI 2018, 'Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: Results from the phase III, randomized ATLAS trial', Annals of Oncology, vol. 29, no. 12, pp. 2371-2378. https://doi.org/10.1093/annonc/mdy454
Gross-Goupil, M. ; Kwon, T. G. ; Eto, Masatoshi ; Ye, D. ; Miyake, H. ; Seo, S. I. ; Byun, S. S. ; Lee, J. L. ; Master, V. ; Jin, J. ; DeBenedetto, R. ; Linke, R. ; Casey, M. ; Rosbrook, B. ; Lechuga, M. ; Valota, O. ; Grande, E. ; Quinn, D. I. / Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma : Results from the phase III, randomized ATLAS trial. In: Annals of Oncology. 2018 ; Vol. 29, No. 12. pp. 2371-2378.
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title = "Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: Results from the phase III, randomized ATLAS trial",
abstract = "Background: The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methods: In a phase III, randomized, double-blind trial, patients had >50{\%} clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [pT2 and/or N{\th}, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1: 1) oral twice-daily axitinib 5 mg or placebo for 3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG 3 or pT4 and/or N{\th}, any T, any FG) was conducted. Results: A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) ¼ 0.870; 95{\%} confidence interval (CI): 0.660-1.147; P ¼ 0.3211). In the highest-risk subpopulation, a 36{\%} and 27{\%} reduction in risk of a DFS event (HR; 95{\%} CI) was observed per investigator (0.641; 0.468-0.879; P ¼ 0.0051), and by IRC (0.735; 0.525-1.028; P ¼ 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99{\%} versus 92{\%}) and serious AEs (19{\%} versus 14{\%}), but more grade 3/4 AEs (61{\%} versus 30{\%}) were reported for axitinib versus placebo. Conclusions: ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration number: NCT01599754.",
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T1 - Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma

T2 - Results from the phase III, randomized ATLAS trial

AU - Gross-Goupil, M.

AU - Kwon, T. G.

AU - Eto, Masatoshi

AU - Ye, D.

AU - Miyake, H.

AU - Seo, S. I.

AU - Byun, S. S.

AU - Lee, J. L.

AU - Master, V.

AU - Jin, J.

AU - DeBenedetto, R.

AU - Linke, R.

AU - Casey, M.

AU - Rosbrook, B.

AU - Lechuga, M.

AU - Valota, O.

AU - Grande, E.

AU - Quinn, D. I.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methods: In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [pT2 and/or Nþ, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1: 1) oral twice-daily axitinib 5 mg or placebo for 3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG 3 or pT4 and/or Nþ, any T, any FG) was conducted. Results: A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) ¼ 0.870; 95% confidence interval (CI): 0.660-1.147; P ¼ 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468-0.879; P ¼ 0.0051), and by IRC (0.735; 0.525-1.028; P ¼ 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo. Conclusions: ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration number: NCT01599754.

AB - Background: The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methods: In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [pT2 and/or Nþ, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1: 1) oral twice-daily axitinib 5 mg or placebo for 3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG 3 or pT4 and/or Nþ, any T, any FG) was conducted. Results: A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) ¼ 0.870; 95% confidence interval (CI): 0.660-1.147; P ¼ 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468-0.879; P ¼ 0.0051), and by IRC (0.735; 0.525-1.028; P ¼ 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo. Conclusions: ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration number: NCT01599754.

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