{"entity":{"id":"paper-act-in-sarc-lancet-oncol-2019","kind":"paper","name":"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","aka":[],"tldr":"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.\n\nBetween 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.","asOf":"2026-09-24","links":[{"label":"The Lancet Oncology 2019","url":"https://doi.org/10.1016/S1470-2045(19)30326-2"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/31296491/"},{"label":"ClinicalTrials.gov NCT02379845","url":"https://clinicaltrials.gov/study/NCT02379845"}],"tags":[],"related":[],"cancers":["sarcoma"],"sections":[],"technologies":["radiosensitisers"],"targets":[],"drugs":["nbtxr3"],"companies":["nanobiotix"],"institutions":[],"pathways":[],"terms":[],"trials":["act-in-sarc"],"people":["sylvie-bonvalot"],"bottlenecks":[],"keyPapers":[],"journals":["lancet-oncology"],"dependsOn":[],"notes":[],"journal":"The Lancet Oncology","year":2019,"doi":"10.1016/S1470-2045(19)30326-2","pmid":"31296491","authors":"Bonvalot S, Rutkowski PL, Thariat J, et al.","paperType":"rct","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."],"whatItMeans":"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%)."],"changedPractice":true,"participants":180},"route":"/key-papers/paper-act-in-sarc-lancet-oncol-2019/","neighbours":{"cancer":[{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"technology":[{"id":"radiosensitisers","kind":"technology","name":"Radiosensitisers","route":"/technologies/radiosensitisers/"}],"drug":[{"id":"nbtxr3","kind":"drug","name":"NBTXR3 (hafnium oxide nanoparticles)","route":"/drugs/nbtxr3/"}],"company":[{"id":"nanobiotix","kind":"company","name":"Nanobiotix","route":"/companies/nanobiotix/"}],"trial":[{"id":"act-in-sarc","kind":"trial","name":"Act.In.Sarc","route":"/trials/act-in-sarc/"}],"person":[{"id":"sylvie-bonvalot","kind":"person","name":"Sylvie Bonvalot","route":"/people/sylvie-bonvalot/"}],"journal":[{"id":"lancet-oncology","kind":"journal","name":"The Lancet Oncology","route":"/journals/lancet-oncology/"}]}}