Initial safety and tumor control results from a phase I prospective trial evaluating a novel alpha-emitting radionuclide for the treatment of locally advanced recurrent squamous cell carcinomas of the skin and head and neck.

Abstract

e18509 Background: The purpose of this study is to report on the feasibility and safety of Diffusing Alpha-emitters Radiation Therapy (DaRT), including interstitial implantation of a novel alpha-emitting brachytherapy source, to treat locally advanced and recurrent squamous cell carcinomas (SCC) of the skin and head and neck. Methods: This prospective, first-in-human Phase I multicenter study included 28 eligible patients with 31 lesions. The primary endpoint was the feasibility and safety of the DaRT treatment approach. The secondary endpoint was initial tumor response and local progression-free survival (PFS) outcomes. Eligibility criteria included biopsy-proven SCC of the skin and head neck with either recurrent or previously-treated disease with either surgery or prior external beam radiotherapy. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (Version 4.03). Tumor response was assessed at follow-up (30-45 days following treatment) using the Response Evaluation Criteria in Solid Tumors (Version 1.1). Results: Acute toxicity events included mostly erythema and swelling at the implantation site followed by pain and mild skin ulceration. Pain and Grade 2 skin ulcerations resolved in most patients within 3-5 weeks. Complete response (CR) to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 78.6%); seven lesions (6/28; 21.4%) manifested a partial response ( > 30% tumor reduction). Among the 22 lesions with a CR, 5 (22%) developed a subsequent local relapse at the site of DaRT implantation at a median of 4.9 months (range: 2.43-5.52 months). The one-year local PFS probability at the implanted site was 60% (95% Confidence Interval, CI: -28.61-81.35%) for complete responders. Overall survival (OS) at 12 months post-DaRT implantation was 75% (95% CI: 46.14-89.99%); among complete responders, OS was 93% (95% CI: 59.08-98.96%). Conclusions: Alpha-emitter brachytherapy using DaRT achieved significant tumor responses without Grade 3 or higher toxicities. Longer follow-up observations and larger studies are underway to validate these findings. Clinical trial information: NCT03015883 NCT03353077.