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
Publication statusPublished - Jan 1 2018

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

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    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. (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