Adjuvant platinum-based chemotherapy is associated with delayed metastasis among patients diagnosed with upper-tract urothelial carcinoma (UTUC), according to findings from the phase III POUT trial, presented (abstract 407) at the 2018 Genitourinary Cancers Symposium, held February 8–10 in San Francisco.
“Adjuvant platinum-based chemotherapy within 90 days following nephroureterectomy improved disease-free survival and metastasis-free survival in UTUC,” reported lead study author Alison J. Birtle, MRCP, FRCR, MD, of the Lancashire Teaching Hospitals, NHS Foundation Trust, in Preston, United Kingdom.
Based on the findings, adjuvant platinum-based chemotherapy should be considered a new standard of care for these patients, Dr. Birtle and coauthors concluded.
POUT was closed to recruitment early as the protocol defined an early stopping rule once efficacy was met, they noted.
There has been insufficient evidence to recommend adjuvant systemic chemotherapy. The study team sought to evaluate 3-year disease-free survival (defined as time from randomization to death from any cause, recurrence, or metastasis) and metastasis-free survival for patients who undergo supportive care plus either adjuvant platinum-based (gemcitabine/cisplatin or gemcitabine/carboplatin) chemotherapy or surveillance.
Between 2012 and 2017, 261 patients were initially enrolled in the study at 57 UK cancer centers; one patient withdrew consent, leaving 260 patients in the intent-to-treat (ITT) study population. Eligibility criteria included histologically confirmed, nonmetastatic upper-tract urothelial/transitional cell carcinoma with T2–T4 tumors with or without nodal involvement. After 131 patients were randomly assigned to the chemotherapy group, 124 received chemotherapy and seven withdrew from the study. Another 129 patients were assigned to the surveillance study group, of whom three withdrew.
Disease-free survival was superior for the adjuvant chemotherapy group compared with the surveillance group (disease-free survival hazard ratio [HR], 0.49; 95% CI, 0.31–0.76; P = .001). The finding remained statistically significant after controlling for nodal involvement, chemotherapy type, and microscopic surgical margin status. Two-year disease-free survival was 70% with chemotherapy vs 51% with surveillance.
Metastasis-free survival was also significantly better among patients in the chemotherapy study group (HR, 0.49; 95% CI, 0.30–0.78; P = .002).
Toxicity data were available for 257 patients, with grade 3 or higher adverse events reported for 53% in the chemotherapy group vs 13.5% in the surveillance group. The most frequent chemotherapy-associated adverse events included neutrophil count decline (24.3% and 37.3% among patients receiving cisplatin and carboplatin, respectively), platelet count declines (7.1%, 11.8%), febrile neutropenia (5.7%, 7.8%), hearing impairment (5.9% of patients receiving gemcitabine and carboplatin), and nausea (2.9%, 1.4%) or vomiting (7.8%, 9.8%).
Follow-up for overall survival outcomes is ongoing, the authors reported.