TY - JOUR
T1 - Randomized Trial of Two Induction Therapy Regimens for High-Risk Neuroblastoma
T2 - HR-NBL1.5 International Society of Pediatric Oncology European Neuroblastoma Group Study
AU - Garaventa, Alberto
AU - Poetschger, Ulrike
AU - Valteau-Couanet, Dominique
AU - Luksch, Roberto
AU - Castel, Victoria
AU - Elliott, Martin
AU - Ash, Shifra
AU - Chan, Godfrey C.F.
AU - Laureys, Geneviève
AU - Beck-Popovic, Maja
AU - Vettenranta, Kim
AU - Balwierz, Walentyna
AU - Schroeder, Henrik
AU - Owens, Cormac
AU - Cesen, Maja
AU - Papadakis, Vassilios
AU - Trahair, Toby
AU - Schleiermacher, Gudrun
AU - Ambros, Peter
AU - Sorrentino, Stefania
AU - Pearson, Andrew D.J.
AU - Ladenstein, Ruth Lydia
N1 - Publisher Copyright:
© 2021 by American Society of Clinical Oncology.
PY - 2021/8/10
Y1 - 2021/8/10
N2 - PURPOSE Induction therapy is a critical component of the therapy of high-risk neuroblastoma. We aimed to assess if the Memorial Sloan Kettering Cancer Center (MSKCC) N5 induction regimen (MSKCC-N5) would improve metastatic complete response (mCR) rate and 3-year event-free survival (EFS) compared with rapid COJEC (rCOJEC; cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C]). PATIENTS AND METHODS Patients (age 1-20 years) with stage 4 neuroblastoma or stage 4/4s aged, 1 year with MYCN amplification were eligible for random assignment to rCOJEC or MSKCC-N5. Random assignment was stratified according to national group and metastatic sites. Following induction, therapy comprised primary tumor resection, high-dose busulfan and melphalan, radiotherapy to the primary tumor site, and isotretinoin with ch14.18/CHO (dinutuximab beta) antibody with or without interleukin-2 immunotherapy. The primary end points were mCR rate and 3-year EFS. RESULTS A total of six hundred thirty patients were randomly assigned to receive rCOJEC (n 5 313) or MSKCCN5 (n 5 317). Median age at diagnosis was 3.2 years (range, 1 month to 20 years), and 16 were younger than 1 year of age with MYCN amplification. mCR rate following rCOJEC induction (32%, 86/272 evaluable patients) was not significantly different from 35% (99/281) with MSKCC-N5 (P 5 .368), and 3-year EFS was 44% 6 3% for rCOJEC compared with 47% 6 3% for MSKCC-N5 (P 5 .527). Three-year overall survival was 60% 6 3% for rCOJEC compared with 65% 6 3% for MSKCC-N5 (P 5 .379). Toxic death rates with both regimens were 1%. However, nonhematologic CTC grade 3 and 4 toxicities were higher with MSKCC-N5: 68% (193/283) versus 48% (129/268) (P, .001); infection 35% versus 25% (P 5 .011); stomatitis 25% versus 3% (P, .001); nausea and vomiting 17% versus 7% (P, .001); and diarrhea 7% versus 3% (P 5 .011). CONCLUSION No difference in outcome was observed between rCOJEC and MSKCC-N5; however, acute toxicity was less with rCOJEC, and therefore rCOJEC is the preferred induction regimen for International Society of Pediatric Oncology European Neuroblastoma Group.
AB - PURPOSE Induction therapy is a critical component of the therapy of high-risk neuroblastoma. We aimed to assess if the Memorial Sloan Kettering Cancer Center (MSKCC) N5 induction regimen (MSKCC-N5) would improve metastatic complete response (mCR) rate and 3-year event-free survival (EFS) compared with rapid COJEC (rCOJEC; cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C]). PATIENTS AND METHODS Patients (age 1-20 years) with stage 4 neuroblastoma or stage 4/4s aged, 1 year with MYCN amplification were eligible for random assignment to rCOJEC or MSKCC-N5. Random assignment was stratified according to national group and metastatic sites. Following induction, therapy comprised primary tumor resection, high-dose busulfan and melphalan, radiotherapy to the primary tumor site, and isotretinoin with ch14.18/CHO (dinutuximab beta) antibody with or without interleukin-2 immunotherapy. The primary end points were mCR rate and 3-year EFS. RESULTS A total of six hundred thirty patients were randomly assigned to receive rCOJEC (n 5 313) or MSKCCN5 (n 5 317). Median age at diagnosis was 3.2 years (range, 1 month to 20 years), and 16 were younger than 1 year of age with MYCN amplification. mCR rate following rCOJEC induction (32%, 86/272 evaluable patients) was not significantly different from 35% (99/281) with MSKCC-N5 (P 5 .368), and 3-year EFS was 44% 6 3% for rCOJEC compared with 47% 6 3% for MSKCC-N5 (P 5 .527). Three-year overall survival was 60% 6 3% for rCOJEC compared with 65% 6 3% for MSKCC-N5 (P 5 .379). Toxic death rates with both regimens were 1%. However, nonhematologic CTC grade 3 and 4 toxicities were higher with MSKCC-N5: 68% (193/283) versus 48% (129/268) (P, .001); infection 35% versus 25% (P 5 .011); stomatitis 25% versus 3% (P, .001); nausea and vomiting 17% versus 7% (P, .001); and diarrhea 7% versus 3% (P 5 .011). CONCLUSION No difference in outcome was observed between rCOJEC and MSKCC-N5; however, acute toxicity was less with rCOJEC, and therefore rCOJEC is the preferred induction regimen for International Society of Pediatric Oncology European Neuroblastoma Group.
UR - http://www.scopus.com/inward/record.url?scp=85114066243&partnerID=8YFLogxK
U2 - 10.1200/JCO.20.03144
DO - 10.1200/JCO.20.03144
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C2 - 34152804
AN - SCOPUS:85114066243
SN - 0732-183X
VL - 39
SP - 2552
EP - 2563
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 23
ER -
