A Phase Ib Case Series Using Bortezomib With Chemotherapy in Atypical Teratoid/Rhabdoid Tumors.

Atypical teratoid/rhabdoid tumors (ATRTs) are aggressive pediatric brain tumors that are sensitive to proteasome inhibitors in preclinical models. We evaluated the feasibility of combining the proteasome inhibitor, bortezomib, with chemotherapy. Six patients aged 0.8-13 years with newly diagnosed ATRT were enrolled from January 2022 through December 2023. Bortezomib was given intravenously at the dose of 1.3 mg/m2/day on days 1, 4, 8, and 11 of a 21-day chemotherapy cycle for 6 cycles. Radiation therapy was given before initiation of chemotherapy in 4 patients or at the end of chemotherapy in one patient. The primary endpoint was grade 3 or higher non-hematologic toxicities. Thirty cycles of bortezomib with chemotherapy were evaluated. No grade 3 or higher toxicities were considered bortezomib-related. Four patients completed 6 cycles of bortezomib; 2 patients discontinued treatment due to progressive disease after 2 and 4 cycles, respectively. An additional 6 cycles of bortezomib were evaluated after high-dose chemotherapy in three patients without grade 4 bortezomib-related toxicity. Five patients had a near-total resection; one patient had a subtotal resection. Four patients were evaluable for response with 2 partial responses, 1 stable disease, and 1 progressive disease. Two patients without measurable tumor after surgery were not evaluable for response. Two patients remain alive without disease at 37 and 40 months, and one patient died without disease at 19 months after diagnosis. Three patients died with progressive disease. The toxicities were no more than expected with chemotherapy alone. Adding bortezomib to treatment of ATRT is feasible. NCT06853080.