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Precision medicine techniques show promise for pediatric patients with relapsed, refractory cancer
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The incorporation of integrative clinical sequencing data into the management of relapsed, refractory or rare cancers in children or young adults appeared feasible and led to treatment changes and family genetic counselling in some patients, according to findings from an ongoing single-center case series.
“We have made significant strides in cancer treatment but for some kids, especially those with metastatic or relapsed disease, even the most advanced, proven therapies have not been able to improve their outcome,” Rajen J. Mody, MD, MS, MBBS, associate professor of pediatrics at University of Michigan, said in a press release. “Our approach in precision oncology showed its greatest promise in these difficult-to-treat patients — 80% of our study patients had relapsed or refractory disease, and those are the ones who benefitted most from our study.”
The current analysis includes data from the first 102 consecutive case patients (median age, 11.5 years; range, 0-22) enrolled in the study. Patients had relapsed, refractory or rare cancers treated at University of Michigan C.S. Mott Children’s Hospital between May, 2012 and October, 2014.
Patients underwent integrative clinical exome and transcriptome sequencing and genetic counselling. Researchers made recommendations to patients’ families after a discussion of the results by a precision medicine tumor board.
The proportion of patients with potentially clinically actionable findings, results of clinical actions based on integrative clinical sequencing and the estimated proportion of patients or families at risk for future cancer served as the main study measures.
Eighty-nine percent of patients (n = 91) had adequate tumor tissue to complete genomic sequencing. Researchers included data from these 91 patients — 31% of whom had hematologic malignancies and 69% solid tumors — in all analyses.
Overall, 46% of the patients had actionable genomic findings that brought about a change in cancer management. This included 54% of the patients with hematologic malignancies and 43% of the patients with solid tumors.
Based on the findings, individualized action was taken in 25% of the cases (n = 23). Fourteen patients received treatment changes and nine patients received genetic counselling for future cancer risk.
Ten percent of these interventions (n = 9) conferred partial remissions between 8 and 16 months or a complete clinical remission between 6 and 21 months.
All nine patients with actionable incidental genetic findings and their families agreed to genetic counselling and screening.
Arul M. Chinnaiyan
“We were excited to see an actionable finding in such a substantial percentage of patients, and we think it could be potentially higher over time,” Arul M. Chinnaiyan, MD, PhD, the S.P. Hicks endowed professor of pathology and director of Michigan Center for Translational Pathology at University of Michigan, said in the release. “These are patients who had exhausted all proven therapeutic options or who had an extremely rare diagnosis. If we can find a clinically actionable event and have a chance to act upon it, we show in this study that it can have a big impact on that patient.”
The researchers noted that a lack of a control group in this study limited their ability to assess whether better outcomes were a result of the integrated sequencing or if they would have been comparable with standard care. Additionally, it takes up to 2 months to report findings from the sequencing to the physicians and patients, and although all costs were covered in the clinical trial as part of the research protocol, cost for sequencing is approximately $6,000 per patient, which could be prohibitive for some patients in a real-world setting.
Yet, the investigators are optimistic about the future of precision medicine, costs for which should decrease over time.
“These are early days and the full promise of precision medicine is yet to be fully realized,” Mody said in the release. “We need better targeted therapies designed for children and turnaround time for sequencing needs to be less than 2 weeks for it to be a regular part of a patient’s treatment plan.”
These results show precision medicine approaches that have been evolving for adult patients with cancer may also apply to the pediatric population, Robert W. Schnepp, MD, PhD, pediatric hematologist-oncologist from the Children’s Hospital of Philadelphia, and colleagues wrote in an accompanying editorial. However, that many patients with potentially actionable findings did not receive treatment because researchers could not identify a drug that may have benefited them is a “troubling reality,” Schnepp and colleagues wrote.
“Reasons cited ranged from lack of pediatric dosing information to no available clinical trial,” they added. “The pediatric oncology community will need to completely rethink models of drug development in the genomic era as rare diseases become even more rare based on genetically defined subsets. Academic, federal and industry leaders must overcome the current risk-aversion mentality that interferes with translational innovation and develop new mechanisms to more deftly develop and deliver drugs to children with cancer.”– by Anthony SanFilippo
Disclosure: Chinnaiyan reports a consultant/advisory role with Paradigm Diagnostics. Mody and Schnepp report no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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