Getting patients enrolled in clinical trials in general continues to be a challenge, but there is good news in the area of pediatric oncology: Researchers reported a high prevalence of population-wide clinical trial participation among North American children with intermediate- or high-risk neuroblastoma.
In an analysis of enrollment in the International Neuroblastoma Risk Group (INRG) Data Commons, 43.9% (n=3,986/9,087) of patients with neuroblastoma were enrolled in upfront clinical trials, according to Mark A. Applebaum, MD, of the University of Chicago, and co-authors.
Specifically, 3,058 children with intermediate-risk neuroblastoma (50.1% boys; mean age 10.7 months) and 6,029 children with high-risk neuroblastoma (57.9% boys; mean age 45.8 months) were enrolled in a Children’s Oncology Group or legacy group neuroblastoma biology study between 1991 and 2020. Also, 1,513 patients with intermediate-risk neuroblastoma (49.5%) and 2,473 patients with high-risk neuroblastoma (41.0%) were enrolled in a clinical trial, they wrote in JAMA Network Open.
While the majority of children were White—ranging from about 81% in the high-risk group up to about 87% in the intermediate-risk group—the authors reported that “representation of patients from racial/ethnic minority groups was similar in both cohorts.” Previous research has shown that “major barriers to clinical trial enrollment for pediatric cancer minority participants included language discordance, travel difficulties, and complex trial designs.”
Finally, the authors found that overall survival (OS) differed between the risk groups even if they took part in a trial.
“Compared with children not enrolled in clinical trials, a higher prevalence of favorable prognostic markers was identified among patients with intermediate-risk neuroblastoma enrolled in clinical trials, and unfavorable features were more prevalent among patients with high-risk neuroblastoma enrolled in clinical trials…Participation in a clinical trial was not associated with OS in this cohort, likely reflecting the common practice of treating nontrial participants with therapeutic and supportive care regimens used in a previous therapeutic trial,” Applebaum’s group explained.
Multiple clinical trials have demonstrated that patients with intermediate-risk disease achieve “excellent outcomes” with surgery and moderate-dose chemotherapy, while those with high-risk disease benefit from “intensive, multimodality treatments,” according to the authors, but “participation in an unproven therapeutic trial carries risk, and the experimental nature of trials may cause anxiety for patients and families… more than half of all patients with neuroblastoma are not treated in a clinical trial owing to many factors, including family and clinician preference and receiving a diagnosis when no open trial is available.”
Using INRG Data Commons, they analyzed the potential benefit linked with participating in a clinical trial, comparing the outcome of 3,986 trial enrollees with intermediate- or high-risk neuroblastoma with the outcome in 5,101 patients not enrolled in a trial but treated with standard of care. The main outcomes for the current study were event-free survival (EFS) and OS of patients enrolled in an upfront Children’s Oncology Group (COG) clinical trial versus a biology study alone.
Applebaum’s group found that, for those with intermediate-risk disease, there was no difference in EFS between patients from 1991 to 2011 (2006 was excluded because no studies were open that year) versus biology study enrollees in those same years at 85% (95% CI 83% to 87%) versus 87% (95% CI 84% to 90%) at 10 years (P=0.08).
However, a significantly lower EFS was observed for patients who participated in two trials (COG A3973 and COG 3891) versus those only in a biology study who received a diagnosis between 1991 and 1997 or between 2001 and 2006 at 32% (95% CI 29% to 35%) versus 38% (95% CI 35% to 41%), respectively, at 10 years (P<0.001).
OS was higher among those with intermediate-risk neuroblastoma who took part in a clinical trial versus those only in a biology study at 95% (95% CI 94% to 96%] versus 91% (95% CI 89% to 94%, P=0.01), respectively. But clinical trial patients with high-risk disease did not seem to see an OS benefit at 38% (95% CI 35% to 41%] versus 41% (95% CI 38% to 44%) for the biology study group (P=0.23).
The authors also noted that “[c]ompared with children not enrolled in clinical trials, a higher prevalence of favorable prognostic markers was identified among patients with intermediate-risk neuroblastoma enrolled in clinical trials, and unfavorable features were more prevalent among patients with high-risk neuroblastoma enrolled in clinical trials.”
Applebaum’s group acknowledged that other studies have highlighted “discrepancies in clinical trial enrollment according to demographic features, such as…race/ethnicity,” but “we found no evidence of bias in recruitment across demographic groups.” They pointed out that 12.9% of the cohort in their study was Black and 11.3% were Hispanic, “mirroring the prevalence of Black and Hispanic individuals in the US population and in the overall neuroblastoma population in North America.”
They also noted that “we are unable to assess how other social determinants of health that disproportionally affect minority populations may be associated with adherence to protocol therapy,” although IV treatment for neuroblastoma is almost always done in a hospital or clinic with close monitoring.
Study limitations included lack of information in INRG Data Commons about the specific treatment patients received. Applebaum’s group explained that “postconsolidation immunotherapy has been shown to improve survival for patients with high-risk neuroblastoma, outcomes data from the immunotherapy expansion arm of ANBL0032 trial of dinutuximab (Unituxin) were not available in INRG. On a related note, researchers in Italy recently outlined the future of immunotherapies in neuroblastoma.
And researchers have offered strategies on recruiting patients for pediatric clinical trials, including boosting minority enrollment.
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About 44% of patients in a large cohort of patients with neuroblastoma from the International Neuroblastoma Risk Group (INRG) Data Commons were enrolled in upfront clinical trials.
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Overall survival differed between patients with intermediate-risk disease versus those with high-risk disease, even if they took part in a trial, but representation of patients from racial/ethnic minority groups was similar in both groups.
Shalmali Pal, Contributing Writer, BreakingMED™
The INRG Data Commons is supported by the William Guy Forbeck Research Foundation, the St Baldrick’s Foundation, the Little Heroes Cancer Research Fund, the Children’s Neuroblastoma Cancer Foundation, the Neuroblastoma Children’s Cancer Foundation, the Super Jake Foundation, and the Alex’s Lemonade Stand Foundation.
Applebaum reported support from the NIH and the National Cancer Institute (NCI), as well as a relationship with Fennec Pharmaceuticals. Co-authors reported support from, and/or relationships with, Alex’s Lemonade Stand Foundation, the Neuroblastoma Children’s Cancer Society, the Children’s Neuroblastoma Cancer Foundation, the Matthew Bittker Foundation, the Elise Anderson Neuroblastoma Research Fund, St Baldrick’s Foundation, Merck, Roche, Jubilant DraxImage, GlaxoSmithKline, Eli Lilly, Ymabs Therapeutics, Pfizer, Viatris, Sanford Health, CVS Accordant, AbbVie, Litmus Health, NIH/NCI, Novartis, Agios, Bristol Myers Squibb, Aileron Therapeutics, Bluebird Bio, ArQule, United Therapeutics, Stryker, Amgen, Jazz Pharmaceuticals, Sanofi, Varex Imaging, Accelerated Medical Diagnostics, Anthem, Cardinal Health, Novo Nordisk, Regeneron, and Zimmer BioMet.
Cat ID: 120
Topic ID: 78,120,730,120,935,130,138,192,925
