Marilyn M Schapira1,2, Evelyn M Stevens3, James E Sharpe4, Lauren Hochman4, Joseph G Reiter4, Shawna R Calhoun4, Shivani A Shah4, Leonard Charles Bailey5,6, Rochelle Bagatell3,5, Jeffrey H Silber4,5,7,8, Eric Tai9, Lamia P Barakat3,5. 1. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 2. Center for Health Equity Research and Promotion (CHERP), Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA. 3. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 4. Center for Outcomes Resarch, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 5. Division of Oncology, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 6. Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 7. Department of Anesthesiology and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 8. Department of Health Care Management, Wharton School, The University of Pennsylvania, Philadelphia, Pennsylvania, USA. 9. Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Abstract
BACKGROUND: Approximately 50% of children with cancer in the United States who are aged <15 years receive primary treatment on a therapeutic clinical trial. To the authors' knowledge, it remains unknown whether trial enrollment has a clinical benefit compared with the best alternative standard therapy and/or off trial (ie, clinical trial effect). The authors conducted a retrospective matched cohort study to compare the morbidity and mortality of pediatric patients with cancer who are treated on a phase 3 clinical trial compared with those receiving standard therapy and/or off trial. METHODS: Subjects were aged birth to 19 years; were diagnosed between 2000 and 2010 with acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), rhabdomyosarcoma, or neuroblastoma; and had received initial treatment at the Children's Hospital of Philadelphia. On-trial and off-trial subjects were matched based on age, race, ethnicity, a diagnosis of Down syndrome (for patients with ALL or AML), prognostic risk level, date of diagnosis, and tumor type. RESULTS: A total of 428 participants were matched in 214 pairs (152 pairs for ALL, 24 pairs for AML, 32 pairs for rhabdomyosarcoma, and 6 pairs for neuroblastoma). The 5-year survival rate did not differ between those treated on trial versus those treated with standard therapy and/or off trial (86.9% vs 82.2%; P = .093). On-trial patients had a 32% lower odds of having worse (higher) mortality-morbidity composite scores, although this did not reach statistical significance (odds ratio, 0.68; 95% confidence interval, 0.45-1.03 [P = .070]). CONCLUSIONS: There was no statistically significant difference in outcomes noted between those patients treated on trial and those treated with standard therapy and/or off trial. However, in partial support of the clinical trial effect, the results of the current study indicate a trend toward more favorable outcomes in children treated on trial compared with those treated with standard therapy and/or off trial. These findings can support decision making regarding enrollment in pediatric phase 3 clinical trials.
BACKGROUND: Approximately 50% of children with cancer in the United States who are aged <15 years receive primary treatment on a therapeutic clinical trial. To the authors' knowledge, it remains unknown whether trial enrollment has a clinical benefit compared with the best alternative standard therapy and/or off trial (ie, clinical trial effect). The authors conducted a retrospective matched cohort study to compare the morbidity and mortality of pediatric patients with cancer who are treated on a phase 3 clinical trial compared with those receiving standard therapy and/or off trial. METHODS: Subjects were aged birth to 19 years; were diagnosed between 2000 and 2010 with acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), rhabdomyosarcoma, or neuroblastoma; and had received initial treatment at the Children's Hospital of Philadelphia. On-trial and off-trial subjects were matched based on age, race, ethnicity, a diagnosis of Down syndrome (for patients with ALL or AML), prognostic risk level, date of diagnosis, and tumor type. RESULTS: A total of 428 participants were matched in 214 pairs (152 pairs for ALL, 24 pairs for AML, 32 pairs for rhabdomyosarcoma, and 6 pairs for neuroblastoma). The 5-year survival rate did not differ between those treated on trial versus those treated with standard therapy and/or off trial (86.9% vs 82.2%; P = .093). On-trial patients had a 32% lower odds of having worse (higher) mortality-morbidity composite scores, although this did not reach statistical significance (odds ratio, 0.68; 95% confidence interval, 0.45-1.03 [P = .070]). CONCLUSIONS: There was no statistically significant difference in outcomes noted between those patients treated on trial and those treated with standard therapy and/or off trial. However, in partial support of the clinical trial effect, the results of the current study indicate a trend toward more favorable outcomes in children treated on trial compared with those treated with standard therapy and/or off trial. These findings can support decision making regarding enrollment in pediatric phase 3 clinical trials.
Authors: Katie Darabos; Lamia P Barakat; Marilyn Schapira; Christine Hill-Kayser; Lisa A Schwartz Journal: J Adolesc Young Adult Oncol Date: 2020-11-18 Impact factor: 2.223
Authors: Skye Balyasny; Sang Mee Lee; Ami V Desai; Samuel L Volchenboum; Arlene Naranjo; Julie R Park; Wendy B London; Susan L Cohn; Mark A Applebaum Journal: JAMA Netw Open Date: 2021-07-01