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, M. 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
StatePublished - 1 Jan 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

Keywords

  • Adjuvant
  • Axitinib
  • Disease-free survival
  • Overall survival
  • Renal cell carcinoma
  • Safety

Cite this

Gross-Goupil, M., Kwon, T. G., Eto, M., Ye, D., Miyake, H., Seo, S. I., ... Quinn, D. I. (2018). Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: Results from the phase III, randomized ATLAS trial. Annals of Oncology, 29(12), 2371-2378. https://doi.org/10.1093/annonc/mdy454
Gross-Goupil, M. ; Kwon, T. G. ; Eto, M. ; 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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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

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, M.; 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

TY - JOUR

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, M.

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.

KW - Adjuvant

KW - Axitinib

KW - Disease-free survival

KW - Overall survival

KW - Renal cell carcinoma

KW - Safety

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U2 - 10.1093/annonc/mdy454

DO - 10.1093/annonc/mdy454

M3 - Article

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AN - SCOPUS:85059285170

VL - 29

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JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 12

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