In a phase II New Approaches to Neuroblastoma Therapy (NANT) consortium study reported in the Journal of Clinical Oncology, DuBois et al found that combining the radiotherapeutic I-131 metaiodobenzylguanidine (MIBG) with vorinostat produced a higher response rate in relapsed or refractory neuroblastoma vs MIBG alone or combined with vincristine/irinotecan.

Study Details

In the U.S./Canadian multicenter trial, 105 eligible and evaluable patients aged 2 to 30 years with at least one MIBG-avid disease site and adequate autologous stem cells were randomly assigned 1:1:1 between July 2014 and November 2019 to receive MIBG alone (n = 36) or with vincristine at 2 mg/m² on day 0 plus irinotecan at 50 mg/m² daily on days 0 to 4 (n = 35) or vorinostat at 180 mg/m² once daily on days 1 to 12 (n = 34). MIBG was given at 18 mCi/kg on day 1 and autologous stem cells (minimum dose = 1.5 × 10⁶ CD34-positive cells/kg) on day 15.

The primary endpoint was objective response on NANT criteria after one treatment course. The study was designed to have an 80% chance of selecting the regimen with the highest response rate on the assumption that the true response rate in the winning group was ≥ 15% higher vs rates in the other two groups.

Response Rates

After one course, a partial response or better was observed in 5 patients (14%, 95% confidence interval [CI] =5%–30%) in the MIBG group, 5 (14%, 95% CI = 5%–31%) in the MIBG plus vincristine/irinotecan group, and 11 (32%, 95% CI = 18%–51%) in the MIBG plus vorinostat group. An additional 5, 5, and 4 patients, respectively, had minor responses.

A total of 6, 11, and 10 patients, respectively, received a second course of therapy. Response rates after one or two courses were 14%, 17%, and 35%; response rates among the 27 patients receiving a second course were 17%, 36%, and 60%.  

Toxicity

Grade ≥ 3 nonhematologic adverse events considered related to study treatment were observed in 19% of the MIBG group, 49% of the MIBG plus vincristine/irinotecan group, and 35% of the MIBG plus vorinostat group. Among grade ≥ 3 nonhematologic adverse events, vomiting occurred in 0%, 17%, and 6% of patients, respectively; diarrhea in 0%, 11%, and 0%; hypokalemia in 3%, 0%, and 9%; anorexia in 0%, 14%, and 3%; and dehydration in 0%, 11%, and 3%. Febrile neutropenia occurred in 6%, 9%, and 0%.

The investigators concluded: “Vorinostat and MIBG is likely the arm with the highest true response rate, with manageable toxicity. Vincristine and irinotecan do not appear to improve the response rate to MIBG and are associated with increased toxicity.”

Steven G. DuBois, MD, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by National Cancer Institute grants, Alex’s Lemonade Stand Foundation, Friends for Life, Children’s Neuroblastoma Cancer Foundation, Merck & Co Inc, and others. For full disclosures of the study authors, visit ascopubs.org.