Nanoparticles and Radiotherapy: A Winning Combination in the Fight Against Cancer
Surgeon and soft-tissue sarcoma specialist Sylvie Bonvalot is the principal investigator in a clinical trial based on using NBTXR3 nanoparticles. Developed by Nanobiotix, they boost the effects of radiotherapy and increase tumor destruction.
This Phase II/III trial validates the mode of action in hafnium nanoparticles injected before radiotherapy. Its findings have just been published in The Lancet Oncology. The trial potentially paves the way for a broad range of clinical applications in soft-tissue sarcomas and possibly other cancers. In addition, it allows for more extensive use of radiotherapy, which is often limited due to the inability of increasing the dose or proximity to sensitive organs.
Multiplying the effects of radiotherapy
Developed by French biotechnology company Nanobiotix, these hafnium nanoparticles (NBTXR3) boost the effects of the radiation used in radiotherapy, thus increasing tumor destruction. Once injected into the tumor, the NBTXR3 nanoparticles multiply the effects of radiation without impacting on surrounding tissue. The radiation interacts with the hafnium, generating nine times more free radicals than in “standard” radiotherapy. Consequently, these free radicals destroy tumor cells: the effects are therefore purely physical.
The findings of this international randomized Phase II/III trial conducted on 176 patients with soft-tissue sarcomas are encouraging: adding pre-operative hafnium nanoparticles improves the results of radiotherapy. What’s more, it is highly effective: twice as many patients (16% vs. 8%) experienced a pathological complete response—defined as the rate of patients presenting less than 5% residual viable cancer cells in the tumor after treatment—with NBTXR3 compared to the control arm.
“These figures are incredible, and demonstrate an undeniable improvement in radiotherapy treatment with a significant number of complete responses. NBTXR3 nanoparticles are in a position to change standards in treatment. This innovative approach will go on to play a role in other indications, and particularly in those where radiotherapy is used alone. We may also be able to reduce radiotherapy doses while achieving the same effects, which could be useful in repeat radiation and pediatrics,” adds the surgeon.
Another of the trial’s endpoints was resection margins status, which assesses the quality of the surgery. The primary objective is to achieve “clean” margins, meaning that no more cancer cells can be found around the edges where the tumor was removed, which can impact on potential relapse and patient survival. This rate was significantly improved in the group that received treatment with the nanoparticles. Finally, no additional or new undesirable effects linked to the radiation was observed in the NBTXR3 group.
The outlook for other cancers is also promising. As Sylvie Bonvalot explains, “We have already shown a superior response with NBTXR3 at an equivalent dose. Since sarcomas are not very radiosensitive, we can expect major advances for other cancers.”
These nanoparticles are also being assessed for use on ENT tumors, in a Phase I early clinical trial coordinated by medical oncologist Prof. Christophe Le Tourneau, Head of the Early Clinical Trials Department (D3i) at Institut Curie. At the ASCO 2019 congress, he shared encouraging results with the medical community: in nine patients out of 13, tumors disappeared when injected with these same hafnium nanoparticles prior to radiotherapy.
Soft-tissue sarcomas develop in the supportive tissues that link the various structures of the body or make up the walls of organs. They can therefore occur in many different parts of the body. The standard treatment for these tumors at the early stage is surgery. “This surgery can be very heavy-going: the tumors to be removed are generally very large, since they have been there for a long time without producing symptoms. When tumors develop in the abdomen, it is sometimes even necessary to remove the neighboring organs to prevent relapses,” explains Sylvie Bonvalot. In order to improve the results of surgery, radiotherapy may be used beforehand to sterilize the surrounding area and reduce the risk of relapse.
Find out more
Bonvalot, S., Rutkowski, P. L., Thariat, J., Carrère, S., Ducassou, A., Sunyach, M. P., ... & Moreno, V. (2019). 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. The Lancet Oncology.