Outcomes among pediatric patients with cancer who are treated on trial versus off trial: A matched cohort study

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.

Keywords: clinical trial; outcomes assessment; pediatric oncology; retrospective studies; trial effect.

FIGURE 1.

Consolidated Standards Of Reporting Trials (CONSORT) diagram for acute lymphocytic leukemia (ALL). CHOP indicates Children’s Hospital of Philadelphia.

FIGURE 2.

Consolidated Standards Of Reporting Trials (CONSORT) diagram for acute myeloid leukemia (AML). CHOP indicates Children’s Hospital of Philadelphia.

FIGURE 3.

Consolidated Standards Of Reporting Trials (CONSORT) diagram for rhabdomyosarcoma (RMS). CHOP indicates Children’s Hospital of Philadelphia.

FIGURE 4.

Consolidated Standards Of Reporting Trials (CONSORT) diagram for neuroblastoma (NB). CHOP indicates Children’s Hospital of Philadelphia.

FIGURE 5.

Survival analysis of patients with the 4 tumor types who were treated on trial versus standard therapy (ST) and/or off trial. The tumor types were acute lymphocytic leukemia, acute myeloid leukemia, rhabdomyosarcoma, or neuroblastoma. The Cox proportional hazard ratio was 0.69 (95% confidence interval, 0.42–1.13; P = .142).