ASCO 2015: Augmenting Standard Therapies Increases Cure Rates for High-Risk Wilms Tumor


Key Points

  • About 5% to 6% of Wilms tumor patients have loss of heterozygosity on chromosomes 1p and 16q, which leads to a higher risk of tumor recurrence.
  • Loss of heterozygosity was detected in 35 patients with stage I/II disease and 52 patients with stage III/IV disease.
  • Augmented therapy increased the relapse-free survival rates to 83.9% for stage I/II and 91.5% for stage III/IV disease. 

Two phase III Children’s Oncology Group studies found that augmenting therapy with additional drugs improved outcomes for children with a high-risk form of Wilms tumor. These patients have a specific chromosomal abnormality associated with a poorer prognosis. In prior research, such patients had 4-year relapse-free survival rates of 74.9% for stage I/II disease and 65.9% for stage III/IV disease. In the new studies, augmented therapy increased the rates to 83.9% for stage I/II and 91.5% for stage III/IV disease. These findings will be presented at the 2015 ASCO Annual Meeting (Abstract 10009). 

Focus on Tailored Therapy

“Tailoring therapy to match each patient’s risk for relapse has been a major focus of pediatric oncology. 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 cure,” said lead study author David B. Dix, MD, a physician at British Columbia Children’s Hospital. “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.”

Wilms tumor is a rare form of kidney cancer that mainly affects children under the age of 5 years. About 500 new cases are diagnosed in North America every year. This study focused on children with so-called favorable-histology Wilms tumor, which accounts for 75% of childhood renal cancers. Of those cancers, about 5% to 6% have a chromosomal abnormality in the tumor that is known as loss of heterozygosity on chromosomes 1p and 16q, which has been associated with a higher risk of relapse.

Study Findings

In the studies, loss of heterozygosity on 1p and 16q was detected in 35 patients with stage I/II disease and 52 patients with stage III/IV disease. For patients with stage I/II disease, the standard therapy (vincristine/dactinomycin chemotherapy) was augmented with the addition of doxorubicin. Patients with stage III/IV disease received Regimen M, where the standard therapy (vincristine/dactinomycin/doxorubicin and radiation therapy) was augmented with four cycles of outpatient cyclophosphamide/etoposide.

At a median follow-up of 3.6 years, the 4-year relapse-free survival rates were 83.9% for stage I/II disease and 91.5% for stage III/IV disease. When comparing these rates with outcomes with standard treatment regimens (75% for early-stage disease and 66% for late-stage disease), these studies suggest that augmentation of therapy markedly improves outcomes for patients with advanced disease. Given the small numbers in the study sample, the benefit is less clear for patients with lower-stage disease but suggestive of an improved outcome.

Overall, the treatment was well tolerated. For stage I/II patients, augmented therapy was not associated with any significant short-term increase in side effects. For stage III/IV patients, the most common severe side effect of Regimen M was suppression of bone marrow function, occurring in 60% of patients; however, the side effect was manageable. According to the authors, Regimen M substantially reduced the number of patients who would otherwise have to undergo intensive relapse therapy. However, the regimen is predicted to be associated with some risk of reduced fertility. The authors recommend a clear discussion with families regarding the risks and benefits of augmented therapy for these higher-risk patients with loss of heterozygosity.

Testing for loss of heterozygosity on chromosomes 1p and 16q is now considered standard of care and is available at the Children’s Oncology Group Biopathology Center at Nationwide Children’s Hospital and several other centers across North America.

This study was supported by the National Institutes of Health.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.