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