Combination treatment with rapamycin, dasatinib, irinotecan, and temozolomide (RIST) improves progression-free survival (PFS) in children and young adults with relapsed or refractory neuroblastoma, when compared to irinotecan plus temozolomide, a phase 2 study suggests. 

In the entire study cohort, there was no improvement in overall survival (OS) with RIST. However, RIST did improve OS among patients with MYCN-amplified disease. 

These results were presented at the ASCO Annual Meeting 2023 by Selim Corbacioglu, MD, PhD, of University Hospital of Regensburg in Germany.  

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The phase 2 RIST-rNB-2011 study ( Identifier: NCT01467986) enrolled patients aged 25 years or younger with relapsed or refractory, stage IV neuroblastoma, 39% of whom had MYCN-amplified disease. The efficacy population included 124 patients who were randomly assigned to receive RIST (n=61) or irinotecan and temozolomide (n=63).

At a median follow-up of 72 months, the median PFS was significantly longer for patients in the RIST arm than those in the control arm — 11 months and 5 months, respectively (hazard ratio [HR], 0.62; 95% CI, 0.42-0.92; P =.019). 

There was a significant improvement in PFS with RIST among patients with MYCN-amplified disease (HR, 0.45; 95% CI, 0.24-0.84; P =.012), but there was no PFS improvement in patients without MYCN amplification (HR, 0.84; 95% CI, 0.51-1.38; P =.492).

In the entire study cohort, the median OS was 20 months in the RIST arm and 16 months in the control arm, a difference that did not reach statistical significance (HR, 0.68; 95% CI, 0.45-1.04; P =.073).

However, OS was significantly improved with RIST in the MYCN-amplified subgroup (HR, 0.51; 95% CI, 0.27-0.96; P =.037). OS was not improved with RIST in patients without MYCN amplification (HR, 0.91; 95% CI, 0.53-1.57; P =.731).

The safety population included 67 patients in the RIST arm and 60 patients in the control arm. Grade 3 or higher toxicities were reported for 97% of the RIST arm and 100% of the control arm. 

Patients in the RIST arm had lower rates of grade 3 or higher anemia (58.2% and 63.3%, respectively) and infections (17.9% vs 21.7%) but a higher rate of grade 3 or higher neutropenia (88.1% vs 80.0%).

Dr Corbacioglu noted that RIST was safe and well tolerated, in addition to improving PFS in the overall population and OS in MYCN-amplified patients. RIST is easily accessible, can be given on an outpatient basis, and has oral and IV formulations available, he added. 

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures. 


Corbacioglu S, Lode HN, Jakob M, et al. Irinotecan and temozolomide combined with dasatinib and rapamycin for patients with relapsed or refractory neuroblastoma: Results of the prospective randomized RIST trial. ASCO 2023. June 2-6, 2023. Abstract 10001.