Axitinib Versus Placebo as an Adjuvant Treatment for 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+, 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.

Trial registration number

NCT01599754