Functional precision medicine-guided approach benefits pediatric patients with cancer
Key takeaways:
- Five out of six patients had a 1.3-fold increase in PFS with the approach vs. their previous regimen.
- The findings add to a growing body of evidence on the clinical utility of functional precision medicine.
A functional precision medicine-guided approach appeared to increase PFS among a small cohort of pediatric patients with recurrent and/or refractory solid and hematologic cancers, according to results of a prospective study.
The findings, presented at American Association for Cancer Research Annual Meeting, showed the value of functional precision medicine profiling in providing deeper insight into individual patient pharmacological response, researchers concluded.
Rationale and methods
Patients with recurrent and/or refractory cancer represent a significant unmet clinical need, as they have generally failed on clinically validated standard of care treatment and must find new options, Diana Azzam, PhD, assistant professor and director of doctoral programs in the department of environmental health sciences at the Robert Stempel College of Public Health and Social Work at Florida International University, told Healio.
“This need is especially pronounced in pediatric cancer, where few options exist beyond a small number of approved treatment regimens,” she said. “However, with hundreds of FDA-approved agents that can be used off-label and with decades of published evidence supporting the clinical impact of the right drug for the right patient, we decided to investigate the feasibility and impact of drug sensitivity testing and genomic profiling to identify off-label therapeutic options for pediatric patients with cancer. The combination of drug sensitivity testing and genomics is a branch of precision medicine termed functional precision medicine.”
Azzam and colleagues sought to examine the efficacy of functional precision medicine in the management of 25 pediatric patients, including four each with Ewing’s sarcoma, osteosarcoma and rhabdomyosarcoma; three each with acute lymphoblastic leukemia and acute myeloid leukemia; and one each with astrocytoma, ependymoma, glioblastoma, malignant rhabdoid tumor, medulloblastoma, neuroblastoma and Wilms’ tumor.
Researchers used a functional ex vivo drug sensitivity test panel that included 40 formulary drugs frequently used at Nicklaus Children’s Hospital in Miami, 47 nonformulary drugs approved by the FDA for cancer treatment, and therapies under investigation in phase 3 and phase 4 clinical trials.
They calculated drug sensitivity scores for each drug based on treatment response to prospectively generate functional precision medicine and molecular data, and then provided treatment recommendations based on that data to a functional precision medicine molecular tumor board for evaluation.
Findings
The researchers received complete functional and molecular profiling data for 19 (76%) patients.
Overall, six patients received functional precision medicine-guided subsequent treatment recommendations.
“One out of seven standard-of-care patients had 1.3-fold higher PFS vs. their previous regimen, with no overall improvement in PFS,” Azzam said. “Conversely, five out of six patients guided by functional precision medicine experienced a 1.3-fold increase in PFS vs. their previous regimen, with a median 8.5-fold improved PFS ratio vs. their previous regimen.”
Researchers additionally found that no cancer subtype appeared differentially represented in either high-level cluster, indicating the significance of functional precision medicine profiling to provide deeper insight into individual patient pharmacologic response, according to the abstract.
Implications
The findings in both hematologic and solid pediatric cancers, as well as recent trial results in drug sensitivity test-guided therapy from Europe, add to a growing body of evidence on the clinical utility of functional precision medicine for recommending treatment options in recurrent and/or refractory patients with cancer, Azzam told Healio.
“Leveraging patient drug sensitivity testing data and next generation high-throughput sequencing data, we are using explainable AI analysis to develop novel pan-cancer drug response biomarker candidates in top-performing agents,” she said.
Azzam and colleagues are currently enrolling 65 new pediatric patients with cancer in South Florida and developing novel drug response biomarkers in a study funded by the National Institutes of Minority Health and Health Disparities.
“Additionally, we are establishing the first academic [Clinical Laboratory Improvement Amendments] lab in Florida providing drug sensitivity testing for clinical decision-making for patients of all ages and cancer types,” she added. “Key next research includes a large-scale randomized interventional study in a single solid cancer type, or a select small number of cancer types, to robustly validate clinical feasibility and clinical impact of functional precision medicine in patients with recurrent or refractory cancer vs. genomics alone and standard-of-care approaches.”
For more information:
Diana Azzam, PhD, can be reached at dazzam@fiu.edu.
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Acanda de la Rocha AM, et al. Abstract LB358. Presented at: American Association for Cancer Research Annual Meeting; April 14-19, 2023; Orlando.
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