In a Children’s Oncology Group (COG) phase III trial reported in JAMA Oncology, Leary et al found that the addition of carboplatin to radiotherapy in pediatric patients with newly diagnosed high-risk medulloblastoma improved event-free survival in the group 3 molecular subgroup but not in others. Among all patients, overall survival differed significantly across molecular subgroups.
Study Details
The trial included 261 evaluable patients aged 3 to 21 years (median = 8.6 years) from COG sites in the United States, Canada, Australia, and New Zealand enrolled between March 2007 and September 2018. Patients were randomly assigned to receive 36-Gy craniospinal radiation therapy and weekly vincristine with (n = 136) or without (n = 125) daily carboplatin, followed by six cycles of maintenance with cisplatin, cyclophosphamide, and vincristine with or without 12 cycles of isotretinoin during and following maintenance. The primary endpoint was event-free survival.
The isotretinoin randomization was stopped for futility at interim analysis. Outcomes of the carboplatin randomization and analysis according to molecular classification of disease were analyzed. The molecular classification analysis included 231 patients (124 in the carboplatin group and 107 in the control group).
In this randomized clinical trial, therapy intensification with carboplatin improved event-free survival by 19% at 5 years for children with high-risk group 3 medulloblastoma. These findings further support the value of an integrated clinical and molecular risk stratification for medulloblastoma.— Leary et al
Tweet this quote
Key Findings
Among all patients, the 5-year event-free survival was 62.9% (95% confidence interval [CI] = 55.6%–70.2%), and the 5-year overall survival was 73.4% (95% CI = 66.7%–80.1%).
The 5-year event-free survival was 66.4% (95% CI = 56.4%–76.4%) in the carboplatin group vs 59.2% (95% CI = 48.8%–69.6%) in the control group (P = .11). Overall survival at 5 years was 77.6% (95% CI = 69.0%–86.2%) in the carboplatin group vs 68.8% (95% CI = 59.0%–78.6%) in the control group (P = .28).
A benefit of carboplatin was observed only in patients with group 3 molecular classification (n = 79), with the 5-year event-free survival of 73.2% vs 53.7% (P = .047) and the 5-year overall survival of 82.8% vs 63.7% (P = .06).
Among all patients in the molecular subgroup analysis, the 5-year overall survival differed significantly (P = .006): rates were 100% in the WNT pathway–activated subgroup (n = 14), 53.6% in the SHH pathway–activated subgroup (n = 37), 73.7% in the group 3 subgroup, and 76.9% in the group 4 subgroup (n = 101).
The investigators concluded: “In this randomized clinical trial, therapy intensification with carboplatin improved event-free survival by 19% at 5 years for children with high-risk group 3 medulloblastoma. These findings further support the value of an integrated clinical and molecular risk stratification for medulloblastoma.”
Sarah E.S. Leary, MD, of Seattle Children’s, the University of Washington School of Medicine, and Fred Hutchinson Cancer Research Center, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was funded by the National Cancer Institute, St. Baldrick’s Foundation, and others. For full disclosures of the study authors, visit jamanetwork.com.
