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Author Notes:

Correspondence to: Dr David I. Quinn, USC Keck School of Medicine Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, Suite 3440, Los Angeles, CA 90033, USA. Tel: +1 323 865 3956; E-mail: diquinn@med.usc.edu

We thank Mahgull Thakur (Safety Risk Lead, Pfizer) for her support in the interpretation of the safety findings and for critically reviewing the manuscript.

Medical writing support was provided by Anne Marie McGonigal, PhD, and Vardit Dror, PhD, of Engage Scientific Solutions, and funded by Pfizer.

MG-G received honoraria from and provided advisory board services to Bristol-Myers Squibb, Ipsen, MSD, Novartis, Pfizer, and Roche.

ME has received honoraria from Bristol-Myers Squibb, Pfizer, Novartis, and Ono Pharmaceuticals.

VM has provided advisory board services to Argos, Janssen, Merck, and Pfizer.

RDB and RL are employees of SFJ Pharmaceuticals.

MC, BR, ML, and OV are employees and shareholders of Pfizer Inc.

EG has received honoraria for ad boards, meetings and/or lectures from Pfizer, BMS, IPSEN, Roche, Eisai, Eusa Pharma, MSD, Sanofi-Genzyme, Adacap, Novartis, Pierre Fabre, Lexicon and Celgene; and received unrestricted research grants from Pfizer, Astra Zeneca, MTEM/Threshold, Roche, IPSEN and Lexicon.

DIQ has provided advisory board services for Pfizer, Bayer, Novartis, Bristol-Myers Squibb, Merck, Exelixis, Genentech, Roche, AstraZeneca, and Astellas.

All remaining authors have declared no conflicts of interest.

Subjects:

Research Funding:

This study was sponsored by Pfizer Inc and SFJ Pharmaceuticals.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • adjuvant
  • axitinib
  • disease-free survival
  • overall survival
  • renal cell carcinoma
  • safety
  • DOUBLE-BLIND
  • OPEN-LABEL
  • HIGH-RISK
  • SORAFENIB
  • SURVEILLANCE
  • NEPHRECTOMY
  • SUNITINIB
  • PAZOPANIB
  • EFFICACY
  • THERAPY

Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial

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Journal Title:

Annals of Oncology

Volume:

Volume 29, Number 12

Publisher:

, Pages 2371-2378

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/).

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