Data Support Use of Adjuvant Chemotherapy in Upper Tract Urothelial Cancer

Updated results from the phase 3 POUT trial support the use of adjuvant chemotherapy in patients with upper tract urothelial cancer, according to researchers.¹ They reported these results in the Journal of Clinical Oncology.

The data showed that patients who received chemotherapy had sustained improvements in disease-free survival (DFS) with 65 months of follow-up. The data also suggested a potential improvement in overall survival (OS) with chemotherapy.

The POUT trial (ClinicalTrials.gov Identifier: NCT01993979) included 261 patients with upper tract urothelial cancer who had muscle-invasive disease or lymph node-positive, nonmetastatic disease. All patients had undergone radical nephroureterectomy.  

The patients were randomly assigned to receive adjuvant chemotherapy (n=132) or surveillance (n=129). Chemotherapy consisted of 4 cycles of gemcitabine (1000 mg/m² on days 1 and 8) and either cisplatin (70 mg/m²) or carboplatin (AUC, 4.5 or 5) on day 1.

The study was closed early because DFS results were superior with chemotherapy. In a prior analysis, at a median follow-up of 30.3 months, chemotherapy was associated with a significant improvement in DFS (hazard ratio [HR], 0.45; 95% CI, 0.30-0.68; P =.0001).²

In the current analysis, at a median follow-up of 65 months, there was a significant improvement in DFS with chemotherapy in a univariable analysis (HR, 0.55; 95% CI, 0.38-0.80; P =.001) and a multivariable analysis (HR, 0.58; 95% CI, 0.40-0.84; P =.004).¹

The 5-year DFS rate was 62% in the chemotherapy arm and 45% in the surveillance arm. The restricted mean survival time (RMST) for DFS was 72 months with chemotherapy and 54 months with surveillance (an 18-month improvement with chemotherapy; P =.003).

Chemotherapy was associated with improved OS in a univariable analysis (HR, 0.68; 95% CI, 0.46-1.00; P =.049), and there was a trend toward improved OS with chemotherapy in a multivariable analysis (HR, 0.76; 95% CI, 0.51-1.12; P =.17).

The 5-year OS rate was 66% in the chemotherapy arm and 57% in the surveillance arm. The RMST for OS was 78 months with chemotherapy and 67 months with surveillance (an 11-month improvement with chemotherapy; P =.036).

“[S]ince POUT was stopped early on the basis of superior DFS with chemotherapy, power for OS analysis was reduced,” the researchers noted. “Nevertheless, a statistically significant OS advantage was seen in univariable analysis (P =.049) and, although nonsignificant, multivariable modeling showed a consistent positive trend. The presence of nonproportional hazards may also affect the power of these analyses; RMST results, which account for this, show a statistically significant OS benefit of 11 months over a 9-year period, with the peak benefit between 3 and 4 years.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original references for complete disclosures.

This article originally appeared on Cancer Therapy Advisor