Study of Novel Radioenhancer NBTXR3 Plus Radiotherapy in Patients With Locally Advanced Soft Tissue Sarcoma

International journal of radiation oncology, biology, physics, 2021 · Bonvalot S, Rutkowski P, Thariat JO, Carrere S, Ducassou A, Sunyach MP, et al.

Authors

S.Bonvalot1, P.Rutkowski2, J.O.Thariat3, S.Carrere4, A.Ducassou5, M.P.Sunyach6, P.Ágoston7, A.Hong8, A.Mervoyer9, M.Rastrelli10, C.LePechoux11, V.Moreno12, R.Li13, B.Tiangco14, Z.Papai15

1 – Curie Institute, Paris, France
2 – Centrum Onkologii-Instytut im. Sklodowskiej-Curie w Warszawie, Warszawa, Poland
3 – Centre François Baclesse, Caen, France
4 – Montpellier Cancer Institute, Montpellier, France
5 – Institut Claudius Regaud – IUCT Oncopôle, Toulouse, France
6 – Centre Leon Berard, Lyon, France
7 – National Institute of Oncology, Budapest, Hungary
8 – Melanoma Institute Australia, Sydney, NSW, Australia
9 – Institut de Cancerologie de l’Ouest-Rene Gauducheau, Saint-Herblain, France
10 – Istituto Oncologico Veneto IRCCS, Padova, Italy
11 – Institut Gustave Roussy, Villejuif, France
12 – Hospital Fundación Jimenez Diaz, Madrid, Spain
13 – St. Luke’s Medical Center, Quezon City, Philippines
14 – The Medical City Cancer Center, Pasay City, Philippines
15 – Magyar Honvedseg Egeszsegugyi Kozpont, Budapest, Hungary

Summary

Purpose/Objective(s): NBTXR3, a novel radioenhancer activated by radiotherapy (RT) demonstrated superior efficacy, as preoperative treatment in patients with locally advanced soft tissue sarcoma (LA STS) compared to RT alone. Primary endpoint of pCR rate (16% vs 8%; P = 0.044) and main secondary endpoint of R0 margin rate (16% vs 8%; P = 0.042) were met while no modification of the early RT-associated safety profile was observed, leading to market authorization. Here we report on the long-term safety, limb function and quality of life.

Materials/Methods: This phase II/III randomized (1:1), international trial included adult patients with LA STS of the extremity or trunk wall, requiring preoperative RT. Patients received either a single intratumoral injection of NBTXR3 (equivalent to 10% of tumor volume, at 53.3g/L), plus EBRT (arm A) or EBRT alone (arm B) (50 Gy in 25 fractions), followed by surgery. Here we report on safety of NBTXR3+RT which was evaluated as secondary endpoint. Data were recorded on the “all treated population” during at least a two-year follow-up. Important parameters related to HR-QoL including functional outcome were studied using the EQ-5D, RNLI, TESS and MSTS questionnaires.

Results: Patients had at least two-year follow-up and the lost to follow-up rate was very low (1.9%). RT-related SAEs were observed in 11.2% (10/89) vs 13.3% (12/90) in A vs B. Post-treatment AEs, any grade, were observed in 51.7% (46/89) vs 57.8% (52/90) and serious post-treatment AEs in 13.5% (12/89) vs 24.4% (22/90) of patients in A vs B. Long-term safety continues to demonstrate that NBTXR3 plus RT has no impact on post-surgical wound complications (24.7% vs 36.7%, A vs B). Furthermore, the evaluation of radiation late toxicities in limbs such as fibrosis, arthrosis and edema that may alter limb function showed no difference between arms (4.5% vs 7.7%, 2.2% vs 0.0% and 6.7% vs 2.2% respectively in A vs B). In addition, sequelae or chronic tissue disturbances at the former tumor localization were similar in both treatment arms, confirming that the increase of energy dose deposit and the physical presence of NBTXR3 did not impact post-treatment limb functions. Accordingly, HR-QoL evaluation yielded no difference in functional outcome. Finally, second primary cancer was observed in 1 patient in arm A and 6 patients in arm B and the intratumoral injection of NBTXR3 did not induce cancer cell seeding at the former tumor site.

Conclusion: These results demonstrate that the use of NBTXR3 did not change the late onset toxicity profile of EBRT, nor modified its bystander effect. Taken together, the long-term safety data presented here, and the previously published efficacy data reinforce the favorable benefit-risk ratio of the use of NBTXR3 in patients with LA STS. NCT02379845

By continuing to use the site, you agree to the use of cookies.En poursuivant votre navigation sur ce site, vous acceptez l’utilisation de cookies. More information.En savoir plus.

The cookie settings on this website are set to “allow cookies” to give you the possibility to switch between languages in a way that this will not interfere with page navigation. If you continue to use this website without changing your cookie settings or you click “Accept” below then you are consenting to this.Par défaut, les paramètres de ce site autorisent les cookies pour vous permettre notamment de naviguer entre les différentes langues disponibles. Nous utilisons des cookies pour vous proposer un site internet facile d'utilisation, sécurisé et fonctionnel. Si vous les autorisez également, cliquez sur « Accepter » ou poursuivez simplement votre navigation.

CloseFermer