In the phase III POUT trial, reported in The Lancet, Alison Birtle, MD, and colleagues found that adjuvant gemcitabine/platinum chemotherapy was associated with improved disease-free survival vs surveillance in patients with locally advanced urothelial carcinoma of the upper urinary tract.
Alison Birtle, MD
As stated by the investigators, “No international consensus [currently] exists on the benefit of adjuvant chemotherapy for patients with urothelial carcinoma of the upper urinary tract after nephroureterectomy with curative intent.”
In the open-label multicenter trial, 260 eligible patients staged with either muscle-invasive (pT2–pT4, any N) or lymph node–positive (any pT, N1–3) metastasis-free (M0) disease with predominantly transitional cell carcinoma histology after nephroureterectomy were randomly assigned between June 2012 and November 2017 to chemotherapy initiated within 90 days after surgery (n = 131) or surveillance (n = 129).
Chemotherapy consisted of four 21-day cycles of either cisplatin at 70 mg/m² or, for patients with glomerular filtration rate < 50 mL/min only, carboplatin area under the curve = 4.5/5 on day 1 plus gemcitabine at 1,000 mg/m² on days 1 and 8. The primary endpoint was disease-free survival in the intention-to-treat population.
A preplanned interim analysis met the efficacy criterion for early trial closure. At a median follow-up of 30.3 months, chemotherapy was associated with significantly improved disease-free survival (hazard ratio [HR] = 0.45, 95% confidence interval [CI] = 0.30–0.68, P = .0001). Disease-free survival was 71% vs 46% at 3 years, and median disease-free survival was not reached vs 29.8 months.
Chemotherapy was associated with reduced risk of metastasis or death (HR = 0.48, P = .0007; 3-year event-free rates of 71% vs 53%). Overall survival data were immature at time of analysis; overall, death had occurred in 24 patients in the chemotherapy group and 38 in the surveillance group.
Grade ≥ 3 adverse events occurred in 44% of the chemotherapy group and 4% of the surveillance group. The most common in the chemotherapy group included decreased neutrophils (36%), decreased platelets (10%), nausea (6%), febrile neutropenia (6%), and vomiting (6%). Serious adverse events were reported in 32% of the chemotherapy group. No treatment-related deaths were reported.
The investigators concluded, “Gemcitabine/platinum combination chemotherapy initiated within 90 days after nephroureterectomy significantly improved disease-free survival in patients with locally advanced urothelial carcinoma of the upper urinary tract. Adjuvant platinum-based chemotherapy should be considered a new standard of care after nephroureterectomy for this patient population.”
Dr. Birtle, of Rosemere Cancer Centre, Royal Preston Hospital, Preston, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Cancer Research UK. For full disclosures of the study authors, visit thelancet.com.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®.