Several sections were devoted to the treatment of pediatric malignancies. In particular, two papers presented at the meeting have the potential to influence current clinical practice.
Approximately 400 children and adolescents in the United States are diagnosed with the rare disease Ewing sarcoma each year. Many patients with Ewing sarcoma are heavily pretreated and have often received intensive chemotherapy. The current treatment of recurrent and primary refractory disease shows a five-year survival rate of only 15%.
The Phase 2/3 rEECur trial was conducted to compare the four most commonly used treatments for recurrent and primary refractory Ewing sarcoma in Europe [11]:
Median OS was 16.8 months for ifosfamide versus 10.4 months for TC. A more significant survival difference was observed for patients less than 14 years old than in elder children. Safety data showed more events of grade 3/4 encephalopathy and kidney toxicity and more frequent discontinuation due to toxicity with ifosfamide versus the TC treatment arm. This may be explained by the higher dose of ifosfamide used in the study compared to that typically used in the clinic.
The importance of this trial is two-fold. Firstly, it answered a question about the comparative efficacy of the most frequently used therapeutic regimens and thus could be considered a practice-changing trial with ifosfamide as a potential chemotherapy backbone in combination with targeted agents. Secondly, this study can potentially change the design of future clinical trials in this disease, providing a foundation for a comparative treatment arm. However, other regimens should also be continued as acceptable comparators in clinical trials if needed to avoid overlapping toxicities or achieve therapeutic synergy.
The study showed that high-dose ifosfamide prolonged median event-free survival by 5.7 months compared with 3.7 months for TC."
Central nervous system (CNS) tumors are the most common solid tumors in children. Another clinical trial in the field of pediatric oncology that might influence the standard of care was conducted in low-grade glioma (LGG) — the most common pediatric brain cancer, accounting for up to 30% of all pediatric CNS tumors. This is a heterogeneous group, with 15-20% of these patients having BRAF V600 mutation. The current standard of care for LGG is a combination of carboplatin and vincristine (CV) and is less effective in patients with BRAF V600–mutant disease.
A randomized Phase 2 study compared the first-line combination of dabrafenib and trametinib versus CV in BRAF V600–mutant LGG [12]. The study results showed a significant difference in ORR of 47% for dabrafenib and trametinib compared to 11% for CV and median PFS of 20.1 versus 7.4 months, respectively. Safety data was also favorable for the combination of dabrafenib and trametinib with fewer grade 3/4 AEs (47% versus 94%) and fewer treatment discontinuations due to AEs (4% versus 18%) than patients in the CV group. These results have the potential to change the standard of care for a first-line systemic treatment for such patients. However, this was a Phase 2 trial with a limited number of patients (110 enrolled), and safety and long-term follow-up data are still being collected.