Addition of Preoperative NBTXR3 to Radiotherapy in Locally Advanced Soft-Tissue Sarcoma
In the phase II/III Act.In.Sarc trial reported in The Lancet Oncology, Bonvalot et al found that preoperative addition of the radioenhancer hafnium oxide nanoparticle NBTXR3 to radiotherapy may improve outcomes in patients with locally advanced soft-tissue sarcoma. The agent acts to increase production of free radicals within the tumor, resulting in increased tumor cell death.
The open-label trial included 176 evaluable patients with locally advanced disease of the extremity or trunk wall from 32 sites in Europe and the Asia/Pacific region. They were randomly assigned between March 2015 and November 2017 to receive preoperative NBTXR3 and external-beam radiotherapy (50 Gy in 25 fractions; n = 87) or radiotherapy alone (n = 89). NBTXR3 was given in a single intratumoral injection at a volume equivalent to 10% of baseline tumor volume at a fixed concentration of 53.3 g/L prior to radiotherapy.
The primary endpoint was the proportion of patients with a pathological complete response.
Response Rate and Toxicity
A pathologic complete response was observed in 14 patients (16%) in the NBTXR3 group vs 7 (8%) in the radiotherapy-alone group (P = .044). Surgical R0 margins were achieved in 77% vs 64% of patients (P = .042).
In both treatment groups, the most common grade 3 to 4 treatment-emergent adverse event was postoperative wound complication (9% of patients in the NBTXR3 group and 9% of patients in the radiotherapy-alone group). The most common grade 3 or 4 adverse events related to NBTXR3 administration were injection site pain (4%) and hypotension (4%); the most common grade 3 or 4 radiotherapy-related adverse event was radiation skin injury in both groups (6% vs 4%). Grade 3 or 4 hypotension occurred in 7% of the NBTXR3 group overall.
Serious adverse events occurred in 39% vs 30% of patients. No treatment-related deaths were observed.
The investigators concluded, “This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers.”
Sylvie Bonvalot, PhD, of the Institut Curie, Paris, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Nanobiotix SA. For full disclosures of the study authors, visit thelancet.com.
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