Oral Presentation Advances in Neuroblastoma Research Congress 2016

Phase II randomized trial of irinotecan/temozolomide (I/T) with temsirolimus (TEM) or dinutuximab plus granulocyte colony stimulating factor (DIN/GMCSF) in children with refractory or relapsed neuroblastoma: a report from the Children’s Oncology Group (COG) (#91)

Rajen Mody 1 , Arlene Naranjo 2 , Collin Van Ryn 2 , Wendy B. London 3 , Alice Yu 4 , Barry L. Shulkin 5 , Marguerite T. Parisi 6 , Sabah Serves 7 , Mitch Diccianni 4 , Paul M. Sondel 8 , John M. Maris 9 , Julie R. Park 10 , Rochelle Bagatell 9
  1. Pediatrics, University of Michigan, Ann Arbor, Michigan, United States
  2. Statistics and Data Center, Children's Oncology Group and the Department of Biostatistics, University of Florida, Gainesville, Florida, United States
  3. Pediatrics, Boston Children's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, United States
  4. Pediatrics, University of California San Diego, San Diego, California, United States
  5. Radiological Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, United States
  6. Radiology, Seattle Children's Hospital/University of Washington, Seattle, Washington, United States
  7. Radiology, The Children's Hospital of Philadelphia/Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  8. Pediatrics, University of Wisconsin, Madison, Wisconsin, United States
  9. Pediatrics, The Children's Hospital of Philadelphia/Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  10. Pediatrics, Seattle Children's Hospital/University of Washington, Seattle, Washington, United States

 

Background: Outcomes for children with relapsed and refractory neuroblastoma are dismal. The combination of I/T has activity in patients with relapsed disease, and the toxicity profile of I/T makes it an excellent backbone for study of new agents. Temsirolimus (TEM) and dinutuximab (DIN) were selected for testing in combination with I/T in subjects with relapsed, progressive or refractory neuroblastoma.

 

Methods: COG ANBL1221, a randomized Phase II selection design trial, compared response and toxicity in subjects treated with I/T in combination with either TEM (Arm A) or DIN/GM-CSF (Arm B). Patients were eligible at first relapse/progression or first designation of primary refractory disease. Randomization was stratified based on prior therapy and MYCN status. Cycles were administered every 21 days. Partial and complete responses (PR, CR) were confirmed centrally.

 

Results: Thirty-five eligible patients were enrolled. Median age was 5.7 years (range 2.1-16.2), 24 pts had measurable disease (12 per arm). The 18 subjects randomized to Arm A received 89 total courses (median 3); 1 PR was observed (5%). The 17 patients randomized to Arm B received 136 total courses (median 6). Nine (53%) had objective responses (4 PR, 5 CR), including responses in 5 of 10 patients with relapsed/progressive disease and 4 of 7 with refractory disease. Among Arm B responders, prior therapy included high dose chemotherapy with stem cell rescue in 5 and anti-GD2 therapy in 3. One patient with rapidly progressive thoracic disease experienced Grade 4 hypoxia during Arm B therapy; no other subject experienced unanticipated toxicity. Arm B met protocol-defined criteria for selection as the optimal combination for further study.

 

Conclusion: I/T/DIN/GM-CSF shows significant anti-tumor activity in patients with relapsed/progressive or refractory neuroblastoma. Additional study of this combination will include evaluation of clinical and biological markers that may identify patients most likely to respond to this active chemo-immunotherapeutic regimen.