A New Preoperative Tumor-Shrinking Nanoparticle Drug for Soft Tissue Sarcoma: NBTXR3

Codenamed NBTXR3, an experimental drug with a nanoparticle structure followed by radiotherapy was found effective and safe in patients with limb (arm-leg) and trunk wall soft tissue sarcoma , according to results presented at ESMO 2018from a phase 2-3 clinical trial that demonstrated this.

Radiotherapy activates NBTXR3 hafnium oxide nanoparticles ; patients with locally advanced soft tissue sarcoma of the limbs and trunk wall, inoperable at diagnosis, who received this treatment had significantly greater tumor shrinkage than patients treated with radiotherapy alone.

This international, multicenter, randomized, open-label phase 2-3 clinical trial was presented by Sylvie Bonvalot, Head of Sarcoma Surgery at the Curie Institute in Paris.

Study details

The NBTXR3-301 study enrolled 180 patients, and results from 176 patients were suitable for efficacy analyses. Patients received neoadjuvant (preoperative tumor-shrinking) treatment after randomization to two arms; one received a single intratumoral (into the tumor) injection of NBTXR3 followed by radiotherapy, while the other received radiotherapy alone.

Tumors in both treatment arms were subsequently surgically removed, and patients were stratified by the histological subtype of soft tissue sarcoma. Although different radiotherapy devices were used, the administered radiotherapy dose was 25 fractions of 2Gy, totaling 50 Gy.

The study's primary (main) endpoint was the pathological complete response rate. Pathological complete response is defined as fewer than %5 viable cancer cells remaining after tumor-shrinking treatment. Secondary endpoints included negative surgical margins (R0 resection) and the safety of the nanoparticle drug.

Compared with radiotherapy alone, "NBTXR3 + radiotherapy" doubled the pathological complete response rate

• The pathological complete response rate in patients treated preoperatively with NBTXR3 + radiotherapy was twice that in those receiving radiotherapy alone: % 16.1 versus % 7.9.

Image above: NBTXR3 nanoparticle administration in a patient with soft tissue sarcoma in the inner right thigh, shown in 3-dimensional tomography.

• The rate of surgery with clear margins (R0 resection) in the nanoparticle group was % 77.0 versus % 64.0.
• Injection-site pain occurred in % 13.5 of patients, and NBTXR3, in % 7.9 of patients, was associated with serious (grade 3 and 4) acute immune reactions (allergy). These side effects were reported to be short-lived, manageable and, in some cases, self-resolving.
• Apart from injection-site reactions, NBTXR3 + radiotherapy was very well tolerated and showed a safety profile similar to radiotherapy alone.

In conclusion, NBTXR3, a nanoparticle drug, was found to be safe to inject intratumorally and capable of activation by radiotherapy. Furthermore, as a treatment enhancing the effectiveness of radiotherapy , it delivers greater energy deposition within the tumor than radiotherapy alone, resulting in increased tumor cell death.

NBTXR3 offers patients with soft tissue sarcoma, for whom desired response rates with current treatments are low and treatment options limited, a new option through nanotechnology , an advanced technique offering promise.

Following promising early clinical studies of NBTXR3, this nanoparticle has now begun to be tested in recurrent / metastatic head and neck cancer, metastatic non-small cell lung cancer, prostate cancer, liver cancer and rectal cancer, in other words, many cancers in which radiotherapy is used.