Axitinib Versus Placebo as an Adjuvant Treatment for Renal Cell Carcinoma: Results From the ATLAS Trial
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+, 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+, any T, any FG) was conducted.
Results
A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from May 8, 2012, to July 1, 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] = 0.870; 95% confidence interval [CI]: 0.660–1.147; P=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=0.0051), and by IRC (0.735; 0.525–1.028; P=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.
Annals of Oncology, mdy454, https://doi.org/10.1093/annonc/mdy454 Published: 20 October 2018
Authors
M. Gross-Goupil,1 T. G. Kwon,2 M. Eto,3 D. Ye,4 H. Miyake,5 S. I. Seo,6 S.-S. Byun,7 J. L. Lee,8 V. Master,9 J. Jin,10 R. DeBenedetto,11 R. Linke,11 M. Casey,12 B. Rosbrook,13 M. Lechuga,14 O. Valota,14 E. Grande, & 15 D. I. Quinn16
Affiliation list
1Department of Medical Oncology, Centre Hospitalier Universitaire de Bordeaux, 2Bordeaux, France; Department of Urology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea; 3Department of Urology, Kyushu University, Fukuoka, Japan; 4Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China; 5Department of Urology, Hamamatsu University, Hamamatsu, Japan; 6Department of Urology, Sungkyunkwan University, Seoul, Republic of Korea; 7Department of Urology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 8Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea; 9Department of Urology, Emory University School of Medicine, Atlanta, GA, USA; 10Department of Urology, Peking University First Hospital and Institute of Urology, Beijing, China; 11SFJ Pharmaceuticals, Inc.,Pleasanton, CA, USA; 12Pfizer Inc, Collegeville, PA, USA; 13Pfizer Oncology, San Diego, CA, USA; 14Pfizer Srl, Global Product Development, Milan, Italy; 15Department of Medical Oncology, MD Anderson Cancer Center, Madrid, Spain; 16Department of Medical Oncology, USC Keck School of Medicine Norris Comprehensive Cancer Center, Los Angeles, CA, USA
Reference:
The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology.