Post-VABB Cavity-Targeted Avidin-Pretargeted [90Y]Y-DOTA-Biotin in Nonpalpable Breast Cancer: A Phase I Activity-Escalation Study (ARTHE)

Background/Objectives: Vacuum-assisted breast biopsy (VABB) is widely used for the diagnosis of nonpalpable breast cancer but is not considered definitive treatment because microscopic residual disease may persist within or around the biopsy cavity. The ARTHE phase I trial evaluated a cavity-targeted radionuclide strategy based on same-session sequential intralesional administration of avidin followed by [90Y]Y-DOTA-biotin after VABB. Methods: Eighteen women with nonpalpable breast cancer measuring ≤15 mm and a skin-to-cavity distance ≥ 13 mm were treated in three sequential activity-escalation cohorts. The primary objective was to assess acute local and systemic safety, including dose-limiting toxicity. The protocol-specified co-primary objective was to evaluate preliminary antitumor activity, assessed as breast-only pathologic complete response (pCR) at surgery. Given the phase I single-arm design, pCR was analyzed descriptively. The protocol-specified secondary objective was patient-specific dosimetry. Additional exploratory assessments included post-injection biodistribution and integration with subsequent breast-conserving surgery. Results: No dose-limiting toxicities, grade ≥ 3 adverse events, clinically relevant hematologic toxicity, treatment discontinuations, hospitalizations, or treatment-related surgical delays were observed. Local toxicity was limited to grade 1 injection-site pain and/or erythema. Post-injection imaging consistently demonstrated focal intralesional localization without clinically relevant extra-lesional uptake. All patients underwent breast-conserving surgery 4–7 weeks after treatment. No residual tumor cellularity (RTC), from either invasive or in situ carcinoma, was identified in the breast surgical specimen in 5/18 patients (27.8%). However, because diagnostic VABB may have removed part or all of the malignant lesion, the absence of residual carcinoma at surgery cannot be attributed specifically to the radionuclide treatment. Conclusions: The intralesional avidin-mediated local trapping strategy using [90Y]Y-DOTA-biotin after VABB was feasible, showed favorable acute and short-term tolerability, was associated with early focal localization on post-injection imaging, and was compatible with standard breast-conserving surgery. Controlled studies are warranted to determine the therapeutic contribution of this post-biopsy cavity-targeted strategy, optimize administered activity, and refine patient selection.