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Augmented therapy improves outcomes for children with high-risk Wilms' tumor
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Augmenting standard therapy with additional agents prolonged EFS for children with favorable histology Wilms’ tumor who had loss of heterozygosity of chromosomes 1p and 16q, according to results of two phase 3 Children’s Oncology Group studies.
Approximately 5% to 6% of children with favorable histology Wilms’ tumor have this chromosomal abnormality, which is associated with a greater risk for relapse, according to study background.
“Tailoring therapy to match each patient’s risk for relapse has been a major focus of pediatric oncology,” David B. Dix, MD, a physician at the British Columbia Children’s Hospital in Vancouver, said in a press release. “For cancers with a low risk of recurrence, we strive to decrease therapy and minimize exposure to potentially toxic agents. On the other hand, we want to augment the therapy for those patients who are at higher risk of relapse so that we can hopefully increase the chance for a cure.
“Our study is an example of successful augmentation of therapy for a higher risk group. We were very encouraged to see that augmentation of therapy can overcome the negative influence of a biologic marker in children with Wilms’ tumor,” Dix said.
Dix and colleagues evaluated data from 35 patients with stage I or stage II Wilms’ tumor and 52 patients with stage III or stage IV Wilms’ tumor who were enrolled on the AREN0533/AREN0532 studies. All patients had loss of heterozygosity at chromosomes 1p and 16q.
Patients with stage I or stage II disease received a standard treatment regimen composed of vincristine and dactinomycin, augmented with doxorubicin. Patients with stage III or stage IV disease received the same combination and radiation therapy — the standard for these patients — augmented with alternating cyclophosphamide and etoposide.
Median follow-up was 3.6 years (range, 0.1-8.1).
Four-year EFS was 83.9% (95% CI, 64.9-93.1) for patients with stage I and stage II disease and
91.5% (95% CI, 78.5-96.8) for patients with stage III and stage IV disease.
Researchers compared these data with outcomes from the National Wilms’ Tumor Study-5, in which patients were treated with the standard regimens. Patients with stage I and stage II disease and loss of heterozygosity demonstrated a 74.9% rate for 4-year EFS, and patients with stage III and IV disease and loss of heterozygosity demonstrated a 65.9% rate for 4-year EFS.
The researchers reported that the augmented treatments were well tolerated. Patients with stage I and stage II disease did not experience any significant short-term increases in adverse events, and 60% of patients with stage III and stage IV disease experienced a manageable suppression of bone marrow function.
The augmented regimen for patients with stage III and stage IV disease may reduce the number of patients who otherwise would need to undergo an intensive relapse therapy, according to the researchers; however, the regimen is predicted to reduce fertility.
“Our committee is particularly encouraged by these results, in that they clearly show evidences that augmentation of therapy can overcome a known adverse biomarker,” Dix said during a press conference. “They also provide encouragement to search for other biomarkers of prognostic significance, ideally found in a higher percentage of patients.” – by Anthony SanFilippo
Reference:
Dix DB, et al. Abstract 10009. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.
Disclosure: The researchers report employment and consultant/advisory roles with, stock ownership in and honoraria and research funding from Amgen, Bayer, BioMedical Systems, DiagnoCure, Elekta, MedSolutions Inc., Merck, Pfizer, Rockland Immunochemicals, SJF Pharmaceuticals and St. Jude Children’s Research Hospital.