Adjuvant platinum-based chemotherapy improves DFS in upper tract urothelial carcinoma
Click Here to Manage Email Alerts
The combination of gemcitabine and platinum chemotherapy administered within 90 days after nephroureterectomy significantly extended DFS among patients with locally advanced upper tract urothelial carcinoma, according to results of the randomized phase 3 POUT trial published in The Lancet.
“The POUT trial stemmed from a need in patients with upper urinary tract cancer, as there were no data on quality of life in this population and no international consensus about the standard of care for patients who had undergone nephroureterectomy with unfavorable pathology. There was a real unmet need for patients and clinicians, which presented a lot of challenges,” Alison J. Birtle, MD, MRCP, FRCR, consultant clinical oncologist at Rosemere Cancer Center at Royal Preston Hospital in the U.K., told Healio.
“[These data have] now changed practice — we have shown that giving platinum-based chemotherapy postoperatively to certain patients results in a real difference in relapse," she added. "Gemcitabine plus cisplatin or gemcitabine plus carboplatin is well-tolerated, with the choice of the second agent based upon renal function.”
Nephroureterectomy followed by surveillance is the standard of care for patients with locally advanced upper tract urothelial carcinoma. However, more than half of these patients die of this rare disease and effective treatment options are needed.
The phase 3 POUT trial aimed to assess the efficacy of systemic platinum-based chemotherapy after nephroureterectomy among patients with upper tract urothelial carcinoma receiving treatment across 57 U.K. hospitals.
Researchers randomly assigned 261 patients (median age, 68.5 years; interquartile range [IQR], 62-74.1) in a 1:1 ratio to surveillance (n = 129) or to four, 21-day cycles of chemotherapy (n = 132) with either 70 mg/m² cisplatin or IV carboplatin area under the curve 4.5 or 5 for glomerular filtration rate less than 50 mL/min only on day 1, followed by 1,000 mg/m² IV gemcitabine on days 1 and 8 of each cycle.
Patients received chemotherapy within 90 days after nephroureterectomy.
Most patients (94%) had stage pT2-T3 disease, and 91% of these patients also had stage N0 disease. Sixty-four percent of patients had a glomerular filtration rate of 50 mL/min or higher.
One patient was excluded from the analysis after withdrawing consent for data use after randomization. Seven patients in the chemotherapy group did not start treatment. Three-quarters of patients in the chemotherapy group received four cycles of treatment.
DFS served as the primary endpoint.
Median follow-up was 30.3 months (IQR, 18-47.5).
Results showed a significant improvement in DFS with adjuvant chemotherapy (HR = 0.45; 95% CI, 0.3-0.68).
In addition, researchers reported 3-year DFS estimates of 71% (95% CI, 61-78) with adjuvant chemotherapy vs. 46% (95% CI, 36-56) with surveillance (absolute difference, 25%; 95% CI, 11-38).
Acute grade 3 or worse treatment-emergent adverse events occurred among 44% of patients assigned chemotherapy vs. 4% of patients assigned surveillance. Researchers reported no treatment-related deaths.
“Four cycles of adjuvant platinum-based chemotherapy started within 90 days of nephroureterectomy should now be the standard of care for these patients,” Birtle told Healio. “There are a number of additional questions we can obtain from the POUT results that could help us better determine preoperatively who benefits the most from chemotherapy after surgery. We have the POUT-T study, which collected blood, urine and histopathological samples from participants in the POUT trial. We are starting to analyze these samples to look at prognostic and predictive markers. In addition, a follow-up study to POUT is currently in the works.” – by Jennifer Southall
For more information:
Alison J. Birtle, MD, MRCP, FRCR, can be reached at Royal Preston Hospital, Preston PR2 9HT, U.K.; email: alison.birtle@lthtr.nhs.uk.
Disclosures: The study was funded by Cancer Research UK. Birtle reports personal fees from Astellas, Bayer, Janssen, Roche and Sanofi-Genzyme outside of the submitted work; and research funding from Sanofi-Genzyme outside of the submitted work. Please see the study for all other authors’ relevant financial disclosures.
Collapse
Click Here to Manage Email Alerts