Eighty-nine patients were assigned to a NBTXR3 plus radiotherapy group, while 90 patients received radiotherapy alone. Patients in the experimental group had 2-fold higher pathological complete response rate than did patients in the control arm (16% vs 8%, respectively; P =.044), and the rate of adverse events, including postoperative wound complications, was similar in both groups.

Daniel P. Nussbaum, MD, of Duke University’s department of surgery in Durham, North Carolina, wrote a commentary to accompany the publication of Act.In.Sarc’s interim results.7 While he noted that patients in the NBTXR3 arm had “improved prevalence of R0 resection and histological tumor necrosis,” he added that the study’s final data “will be necessary to interpret whether the activity of NBTXR3 translates to improvements in meaningful clinical outcomes.”

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Dr Nussbaum also noted, however, that, by response evaluation criteria in solid tumors (RECIST), the objective response rate by MRI was not higher in the NBTXR3 group than among controls. While this might have otherwise pointed to more questionable efficacy than otherwise reported, Dr Nussbaum wrote that “standard radiographic studies might not capture these specific tumor changes on treatment, and that novel radiomic strategies might be needed to detect real-time treatment responses.”

Regardless of the actual complete response rate, it will be impossible to determine whether NBTXR3 improves OS and recurrence outcome among patients with STS until longer-term data become available. Piotr Rutkowski, MD, PhD, of the Maria Sklodowska-Curie

Institute in Warsaw, Poland, told Cancer Therapy Advisor in an email that “it seems that NBTXR3 has some activity in sarcomas because the trial is formally positive, however, from a practical point of view currently I cannot find how to put its role into sarcoma treatment until [local recurrence-free survival] and OS data are known. If one of these more clinically relevant end points is positive, it may be [an] important step for therapy of sarcomas, however, many questions still remain (eg, combination with preoperative chemotherapy, hypofractionated radiotherapy, and so on).”

In the meantime, radiation-enhancing particles appear to be a promising tool for improving results with radiotherapy — perhaps even for various different cancers. “We have another trial opening soon in another area of oncology,” professor Thariat said. “Many tumors will be of interest in the future.”

The long-term results of Act.In.Sarc are expected to be reported during the first half of 2020.

References

  1. Sugiura H, Tsukushi S, Yoshida M, Nishida Y. What is the success of repeat surgical treatment of a local recurrence after initial wide resection of soft tissue sarcomas? Clin Orthop Relat Res. 2018;476(9):1791-1800.
  2. Tap WD, Jones RL, Van Tine BA, et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet. 2016;388(10043):488-497.
  3. Eli Lilly and Company. Lilly reports results of phase 3 soft tissue sarcoma study of lartruvo [news release]. Published January 18, 2019. Accessed September 6, 2019. 
  4. O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet. 2002;359(9325):2235-2241.
  5. Haas RL, Delaney TF, O’Sullivan B, et al. Radiotherapy for management of extremity soft tissue sarcomas: why, when, and where? Int J Radiat Oncol Biol Phys. 2012;84(3):572-580.
  6. Bonvalot S, Rutkowski PL, Thariat J, et al. 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. Lancet Oncol. 2019;20(8):1148-1159.
  7. Nussbaum DP. Nanoparticle augmentation of radiotherapy in sarcoma. Lancet Oncol. 2019;20(8):1046-1048.