# NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial

Source: https://onco.cc/key-papers/paper-act-in-sarc-lancet-oncol-2019/  
OnCo record `paper-act-in-sarc-lancet-oncol-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The primary report of Act.In.Sarc: a single injection of hafnium oxide nanoparticles before preoperative radiotherapy doubled the share of sarcomas with a pathological complete response, from 8 to 16 percent.

## Summary

Phase 2-3 randomised, multicentre, international, open-label trial in adults with locally advanced soft-tissue sarcoma of the extremity or trunk wall requiring preoperative radiotherapy. Patients were randomised 1:1, stratified by histological subtype (myxoid liposarcoma versus others), to a single intratumoural administration of NBTXR3 (volume 10 percent of baseline tumour volume at 53.3 g/L) before external-beam radiotherapy of 50 Gy in 25 fractions, or radiotherapy alone, followed by surgery. The primary endpoint was pathological complete response by a central pathology review board under EORTC guidelines in the intention-to-treat full analysis set.

Between March 2015 and November 2017, 180 eligible patients were randomised and 179 started treatment (89 NBTXR3, 90 radiotherapy alone); 176 were analysed for the primary endpoint after three were found ineligible. Pathological complete response was noted in 14 of 87 (16 percent) in the NBTXR3 group and 7 of 89 (8 percent) with radiotherapy alone (p=0.044). Postoperative wound complication was the most common grade 3 to 4 event in both groups (9 percent each); serious adverse events occurred in 39 versus 30 percent, with no treatment-related deaths.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: The Lancet Oncology
- Year: 2019
- DOI: 10.1016/S1470-2045(19)30326-2
- Authors: Bonvalot S, Rutkowski PL, Thariat J, et al.
- Findings: Pathological complete response 14 of 87 (16%) with NBTXR3 plus radiotherapy vs 7 of 89 (8%) with radiotherapy alone (p=0.044).; 180 patients randomised at international centres between March 2015 and November 2017; 176 analysed for the primary endpoint.; Grade 3 to 4 events related to NBTXR3 administration: injection site pain 4%, hypotension 4%; serious adverse events 39% vs 30%; no treatment-related deaths.
- What it means: This trial validated the radioenhancer mode of action and supported the 2019 European CE mark for NBTXR3 (Hensify) in soft-tissue sarcoma. Whether more pathological complete responses translate into fewer recurrences or longer survival was not shown here; the 2022 follow-up paper reported more R0 resections and no harm to quality of life.
- Caveats: Open-label; pathological complete response is a surrogate, and the trial was not powered for recurrence or survival.; The absolute difference is 8 percentage points with a p value of 0.044.; Serious adverse events were more frequent with NBTXR3 (39% vs 30%).

## Sources

- The Lancet Oncology 2019: https://doi.org/10.1016/S1470-2045(19)30326-2
- PubMed: https://pubmed.ncbi.nlm.nih.gov/31296491/
- ClinicalTrials.gov NCT02379845: https://clinicaltrials.gov/study/NCT02379845

## Connected records

- cancers: [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- technologies: [Radiosensitisers](https://onco.cc/technologies/radiosensitisers/)
- drugs: [NBTXR3 (hafnium oxide nanoparticles)](https://onco.cc/drugs/nbtxr3/)
- companies: [Nanobiotix](https://onco.cc/companies/nanobiotix/)
- trials: [Act.In.Sarc](https://onco.cc/trials/act-in-sarc/)
- people: [Sylvie Bonvalot](https://onco.cc/people/sylvie-bonvalot/)
- journals: [The Lancet Oncology](https://onco.cc/journals/lancet-oncology/)

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