I was reading through the submissions to ANR and found this talk:
A Phase 3 randomized clinical trial (RCT) of tandem myeloablative autologous stem cell transplant (ASCT) using peripheral blood stem cell (PBSC) as consolidation therapy for high-risk neuroblastoma (HR-NB): A Children’s Oncology Group (COG) study (#90)
Julie R Park 1 , Susan G Kreissman 2 , Wendy B London 3 , Arlene Naranjo 4 , Susan L Cohn 5 , Michael D Hogarty 6 , Sheena C Teeney 4 , Daphne Haas-Kogan 3 , Peter J Shaw 7 , John Doski 8 , James Geiger 9 , Sandra W Gorges 10 , Gheetika Khanna 11 , Stephan Voss 3 , John M Maris 6 , Lisa Diller 3 , Stephan Grupp 6
University of Washington, Seattle Children’s Hospital, Seattle, WA, United States
Duke University, Durnham, North Carolina, USA
Dana-Farber/Boston Children’s Cancer and Blood Disorder Center, Harvard Medical School, Boston, MA, USA
Children’s Oncology Group, University of Florida, Gainesville, Florida, USA
University of Chicago, Chicago, Illinois, USA
Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
The Children’s Hospital at Westmead, Sydney, Australia
University of Texas Health Center at San Antonio, San Antonio, Texas, USA
C.S. Mott Children’s Hospital, Ann Arbor, Michigan, USA
University of California, Davis, Sacromento, California, USA
Washington University School of Medicine, St. Louis, Missouri, USA
Background: ASCT improves event-free survival (EFS) for HR-NB. Pilot studies suggest that intensification of myeloablative therapy using tandem ASCT further improves outcome for HR-NB. We conducted a multicenter RCT comparing tandem vs. single consolidation in patients with HR-NB.
Methods: Between 11/2007 and 2/2012, 652 eligible patients (pts) with newly diagnosed HR-NB received induction therapy: 6 cycles of chemotherapy including initial 2 cycles of dose-intensive cyclophosphamide/topotecan followed by PBSC collection. Randomization occurred at end induction to single ASCT with carboplatin-etoposide-melphalan (CEM) or tandem ASCT with thiotepa–cyclophosphamide ASCT followed by a modified CEM (TC:CEM). HR pts with non-MYCN amplified Stage 3 (age>18mos) or Stage 4 (age 12-18 mos) tumors were non-randomly assigned to single ASCT (CEM). EFS and overall survival (OS) were analyzed as intent-to-treat.
Results: Median age at study entry was 3.1 yrs, 88% (n=574 pts) had Stage 4 disease and 38.2% (n=249 tumors) had MYCN amplification. A total of 355 pts were randomized (CEM n=179 pts; TC:CEM n=176 pts) and 27 patients were non-randomly assigned to CEM. Of randomized pts, 249 patients received post-consolidation immunotherapy on COG trials. Treatment-related mortality was 2.6% (Induction n=7 [1%]; Consolidation n=10 [2.8%; n=8 CEM, n=2 TC:CEM]). Rates of severe mucosal, infectious or liver toxicities were similar between arms. 3-year EFS and OS from diagnosis were 51.1±2.0% and 68.2±1.9%, respectively. EFS and OS for randomized cohort are noted in the Table.
Cohorts N 3-yr EFS +/- SE (%) 2-sided p-value 3-yr OS +/- SE (%) 2-sided p-value CEM 179 48.8 ± 4.0 69.0 ± 3.6 TC:CEM 176 61.8 ± 4.1 0.0082 73.8 ± 3.7 0.2563 Immunotherapy CEM 129 55.4 ± 4.6 75.7 ± 3.9 TC:CEM 120 73.7 ± 4.4 0.0009 86.3 ± 3.4 0.0158
Conclusions: Tandem myeloablative consolidation therapy improves survival probability in patients with high-risk neuroblastoma, especially in the setting in post-consolidative immunotherapy
The particular thing that sticks out to me is pushing up event free survival up to 73% after 3 years, which is way better than the 50 figure we are used to. I noticed some people on the forum (@teamjakemom) are having tandem transplants, so this should be some very good news.
I am still very unclear what this means for SIOPEN protocol treatment as the induction under COG is very different and drugs used during transplant under SIOPEN are different (BuMel etc.). I guess this is a good question for the panel at ANR.