Final results from the axig trial: A randomized phase ii clinical trial investigating axitinib alone or in combination with CCNU in patients with recurrent glioblastoma

BACKGROUND: Axitinib is a small molecule TKI with high affinity and specificity for the VEGFRs and has demonstrated anti-tumor activity in patients with recurrent glioblastoma (rGB). METHODS: The AXIG trial (NCT01562197) is a randomized clinical trial investigating at first the activity of axitinib monotherapy (AXI-arm) versus physicians best alternative choice of therapy (Duerinck et al. JNO Mar2016) and, following amendment, axitinib monotherapy versus axitinib plus lomustine (Duerinck et al. ASCO AM2016) in patients with rGB. A pooled analysis including all patients exposed to axitinib was performed. RESULTS: Between August 2011 and July 2015, 78 pts were enrolled in the trial and initiated axitinib monotherapy (N:50; AXI) or axitinib plus lomustine (N:28; AXILOM). Median age was 55y [range 18-80], 50M/28F. Baseline characteristics were well balanced between study arms. Thirteen pts in the AXI-arm crossed-over at the time of progression(AXIseqLOM). Treatment was generally well tolerated. AXILOM pts were at higher risk for grade 3/4 neutropenia (0% vs. 21%) and thrombocytopenia (4% vs 29%). BORR in the AXI arm was 26% (2CR/11PR) vs. 43% in the AXILOM-arm (1CR/11PR). BORR after adding CCNU to axitinib at progression on axitinib (AXIseqLOM) was 1 PR and 8SD. 6mPFS and OS rates were respectively 26% (95% CI 14-38) vs 17% (95% CI 2-32), and 54% (95% CI40-68) vs. 53% (95% CI34-73) for pts treated in the AXI vs. AXILOM-arms. When the time-to-second progression was taken into account for the 9 AXIseqLOM patients who experienced PR or SD following the addition of lomustine at first PD on axitinib, 6-mths PFS was 39% (95% CI21-57). No significant correlation was found between clinical outcome measures and the MGMT promoter methylation status or IDH1/2 mutation status. CONCLUSION: Axitinib has single-agent activity in patients with rGB; upfront combination of axitinib and LOM did not significantly increase progression-free or overall survival in patients with recurrent glioblastoma.