Randomized Phase 2 Trial of Presurgical Androgen Deprivation Therapy With or Without Axitinib in Prostate Cancer Presenting With Lymph Node Metastasis.

Background and objective: Strategies that combine systemic and locoregional therapies are increasingly used in prostate cancer (PC) with lymph node metastasis (LNM) at presentation. We investigated whether the presurgical combination of androgen deprivation therapy (ADT) and the antiangiogenic agent axitinib would be more effective than ADT alone in achieving time off systemic therapy after surgery in these patients.

Methods: Patients with newly diagnosed PC with either clinically detected LNM (cTxN1M0 or cTxNxM1a) or at very high risk for subclinical LNM were treated with ADT for 2 mo and then randomized 2:1 to addition of axitinib to ADT versus continuing ADT alone for an additional 4 mo before surgery and discontinuation of systemic therapy. The primary endpoint was the rate of freedom from treatment failure in the intention-to-treat population at 1 yr postoperatively ("success"). Failure was defined as prostate-specific antigen >1.0 ng/ml, objective progression, or initiation of additional treatment.

Key findings and limitations: Of the 73 patients accrued, 49 received axitinib + ADT and 24 received ADT alone. Of the 49 patients who had surgery on protocol, success was achieved in 26, of whom 22 received axitinib + ADT and four received ADT alone. In the node-positive group of 55 patients, the success rate was 36.8% (95% credible interval [CrI] 22.5-52.5%) for axitinib + ADT and 19.0% (95% CrI 5.7-37.9%) for ADT alone; the probability of a higher success rate with axitinib + ADT was 0.935. The median time to progression was 9.8 mo (95% confidence interval [CI] 7.6-17.4) with axitinib + ADT versus 5.7 mo (95% CI 4.0-11.3) with ADT alone (p = 0.03). Pathologic responses, time to metastatic progression, and overall survival were similar between the arms. There were no grade 4-5 toxicities or unexpected perioperative complications.

Conclusions and clinical implications: In patients with newly diagnosed PC with LNM, a presurgical strategy that combines axitinib + ADT was feasible and was more likely than ADT alone to achieve significant time off treatment. However, the overall efficacy was limited, suggesting that patient selection and more effective combinations are needed.