Tailoring Therapy Ups Cure Rates for Children With Rare Kidney Cancer

According to the AREN0532 and AREN0533 trials, adding additional drugs to a therapy regimen for Wilms tumor in children with high-risk disease improved outcomes.

Micrograph of Wilms tumor from 3-year-old patient

Adding additional drugs to a therapy regimen for Wilms tumor-a rare form of kidney cancer-in children with high-risk forms of the disease improved outcomes. The therapies for high-risk patients, who have a specific chromosomal aberration linked to poorer outcomes, were studied in two phase III Children’s Oncology Group clinical trials, AREN0532 and AREN0533.

At a median follow-up of 3.6 years, the 4-year relapse-free survival rate was 83.9% for patients with stage I or II disease and 91.5% for patients with stage III or IV disease. Outcomes with the standard therapy were 75% for early-stage disease and 66% for late-stage disease.

These data were presented by study author David B. Dix, MD, a physician at the British Columbia Children’s Hospital in Vancouver, at a presscast ahead of the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting.

“It’s very encouraging that we’re making progress for kids with a rare, high-risk form of this disease. The ability to easily identify a small subset of patients with a poorer prognosis means these children can receive treatment that’s right for them, while decreasing side effects for lower-risk patients,” said ASCO President-Elect Julie M. Vose, MD, at the presscast.

Wilms tumors predominantly affect children under the age of 5 years. These tumors make up about 75% of all pediatric kidney cancers. About 500 such cases are diagnosed in the United States every year. About 5% to 6% of Wilms tumors harbor a loss of heterozygosity (LOH) on chromosomes 1p and 16q that has been previously linked to a higher risk for relapse.

These results “clearly show evidence that augmentation of therapy can overcome a known adverse biomarker,” said Dix.

Thirty-five children with stage I/II disease and 52 with stage III/IV disease harboring the LOH on 1p and 16q were identified and treated with vincristine and dactinomycin plus the addition of doxorubicin. Patients with late-stage disease received a regimen of vincristine, dactinomycin, doxorubicin, and radiation therapy to which 4 cycles of cyclophosphamide plus etoposide were added.

This study is an example of how adding additional therapies to a pediatric cancer regimen can improve outcomes for a high-risk group of patients.

According to Dix, the toxicities that patients experienced were expected and manageable. Among patients with stage I/II disease, the addition of doxorubicin did not significantly increase short-term side effects. Among the stage III/IV patients, the most common severe side effect was suppression of bone marrow function, which occurred in 60% of patients. According to the study authors, this regimen reduces the proportion of patients who would require subsequent intensive therapy upon relapse, although the regimen does carry a risk of reduced fertility.

Related Videos
Experts on RCC
Experts on RCC
Data demonstrate the feasibility of automated glomerular filtration rate prediction to decide between partial nephrectomy and radical nephrectomy in kidney cancer, according to an expert from the Cleveland Clinic.
Experts on RCC
Experts on RCC
Early phase trials investigating cellular therapies, bispecific antibodies, and antibody-drug conjugates for refractory kidney cancer may uncover strategies to overcome resistance mechanisms.
Increasing cancer antigen presentation as well as working with tumor cells in and delivering novel cells to the microenvironment may help in overcoming mechanisms of immune checkpoint inhibitor resistance in refractory renal cell carcinoma.
Lenvatinib plus pembrolizumab appears to be the best option for patients with refractory metastatic renal cell carcinoma who are progressing on immunotherapy combinations or are lenvatinib naïve.
Ipilimumab monotherapy does not appear effective in driving complete responses in refractory renal cell carcinoma despite yielding some progression-free survival intervals, according to an expert from the University of Texas Southwestern Medical Center.
An expert from the University of Texas Southwestern Medical Center discusses several phase 3 clinical trials supporting the use of various single-agent and combination immunotherapy regimens for advanced kidney cancer.
Related Content