Sylvie Bonvalot, MD, PhD, HDR, discusses the long-term safety results from the phase 2/3 Act.In.Sarc trial with NBTXR3 and radiotherapy in patients with soft tissue sarcoma.
Treatment with NBTXR3 plus radiotherapy did not negatively affect patient quality-of-life or long-term morbidity, and its favorable safety profile combined with its efficacy further reinforce the favorable risk-benefit ratio for patients with soft-tissue sarcoma, according to Sylvie Bonvalot, MD, PhD, HDR.
Results from a long-term safety analysis of the phase 2/3 Act.In.Sarc trial (NCT02379845), which examined NBTXR3 plus radiotherapy vs radiotherapy alone in patients with soft tissue sarcoma, showed that the rate of serious adverse effects [AEs] were similar among the 2 cohorts. Among those receiving the combination, 40.4% of patients reported a serious AE of any grade vs 35.8% in those receiving radiotherapy alone. Additionally, 12.4% of patients reported a serious AE related to treatment with NBTXR3.1
“The quality-of-life, which was [assessed] by 5 different quality-of-life skills, was the same, with no differences [among the study groups],” Bonvalot said. “Altogether, it is interesting because it is very important that treatment is efficient, [but also that we can] show that with long-term follow-up, we do not have more morbidity or worse quality-of-life.”
In an interview with OncLive®, Bonvalot, the head of sarcoma surgery at Institut Curie, in Paris, France, discussed the long-term safety results from the phase 2/3 Act.In.Sarc trial with NBTXR3 and radiotherapy in patients with soft tissue sarcoma.
Bonvalot: NBTXR3 is a hafnium oxide nanoparticle, and it is activated by radiotherapy and administered by a one-time direct intratumoral injection. It was used for the first time in sarcoma, and sarcoma is the first cancer subtype to achieve a phase 2/3 [trial with this agent]. The interaction of radiotherapy with hafnium generates [approximately 9 times more] electrons than with water. [Moreover], these electrons increase the toxicity on the tumor cells, and there is more [tumor cell death] when radiotherapy interacts with hafnium.
[Last year we published a study in Lancet Oncology showing the] initial results of the primary end point of a phase 2/3, randomized study comparing radiotherapy alone vs radiotherapy plus nanoparticles of hafnium NBTXR3. NBTXR3 was injected the day before starting radiotherapy, directly into the tumor. The radiotherapy was applied 50 Gy, and the patient was operated on 6 weeks later. The primary end point was pathologic complete response [pCR]. It is difficult to appreciate pathological response for soft tissue sarcoma because the tumor may decrease in size, however, this was done according to EORTC guidelines.
The main objective was pCR, and in the group of patients [who received] the nanoparticles and radiotherapy, the CR rate was 16%. In the group who had radiotherapy alone, the pCR rate was 9.9%, so…the primary end point was achieved. Another end point was the R0 resection rate, and there was a 77% [R0 rate in the group with NBTXR3 vs 64% in the group with radiotherapy alone]. It was significant, and in fact, the quality of the resection was better in the group with nanoparticles.
The [data] we presented this year at ASCO is the long-term safety of this study. It is very important because it is very promising to have nanoparticles, which increase the rate of pCR, but it is important to show that there is not an increase of toxicity.
The morbidity of the surgery was quantified during the 6 months following, and the quality of life was quantified according to 5 different [parameters]. As these nanoparticles are now used in other cancer types, especially [in those where] radiotherapy is used alone, it is important to be sure that the safety is okay and that there is not [increased] morbidity. [This is] especially important when [these drugs are] used in tissue that are fragile, like the pancreas or liver.
The [rates of] serious adverse effects [AEs] related to radiotherapy were similar in both groups, with 11% in the group with nanoparticles and 13% in the group of patients treated with radiotherapy alone. In terms of hospitalization due to serious AE related to the surgery, in the group with the nanoparticles, 15.7% of the patients were re-hospitalized, [compared with 24% in] the group with radiotherapy alone. This is interesting because in previous so studies, grade 3 morbidity, hospitalization, or reoperation due to radiotherapy is approximately 30%. [Here], it is a little bit less. Of course, it is a trial, and the patients were selected, but is less than previously [reported]. [Additionally] there was a little bit less in the group with nanoparticles.