Adjuvant Platinum-Based Chemotherapy Potential New Standard of Care for Urothelial Cancer: Presented at EAU

By Chris Berrie

COPENHAGEN, Denmark -- March 21, 2018 -- Adjuvant platinum-based chemotherapy within 90 days after nephroureterectomy shows good long-term tolerance and significantly improves disease-free survival (DFS) and metastasis-free survival (MFS) versus surveillance in patients with invasive upper tract urothelial cancer (UTUC), according to a study presented here at the 33rd Annual European Association of Urology (EAU) Congress.

Although UTUC is relatively rare (~1,400 new cases per year in the United Kingdom), it is generally invasive at diagnosis. Standard treatment remains nephroureterectomy followed by surveillance, although ~50% of patients show local or metastatic recurrence.

“There is a clear unmet need, in terms of the patient population, and there are no previous data,” said Alison Jane Birtle, MD, Rosemere Cancer Centre, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, United Kingdom, on March 19.

Indeed, for neoadjuvant chemotherapy, this appears inadvisable, because difficulties in UTUC staging preoperatively might lead to overtreatment. However, UTUC shares a similar aetiology with muscle invasive bladder cancer, which is known to be chemosensitive, although it remains a difficult setting for clinical trials because of postcystectomy morbidity.

The phase 3 POUT study (NCT01993979) was based on these indications and the relatively low postoperative morbidity with UTUC.

The researchers randomised patients with operable disease (pT2-T4 N0-3 M0) to the intention-to-treat populations of standard surveillance (n = 129) or four 21-day cycles of platinum-based chemotherapy according to their baseline glomerular filtration rate (GFR) (n = 131). Treatment was started within 90 days of nephroureterectomy, with supporting care determined according to local practices.

The chemotherapy cycles were based on gemcitabine 1,000 mg/day on days 1 and 8. In addition, patients with GFRs of ≥50 mL/min received added cisplatin 70 mg/m2 on day 1, and those with GFRs of 30 to 49 mL/min received added carboplatin for areas under the curve of 4.5/5.0 on day 1.

Two-thirds (67.7%) of the patients were men, 74.2% were aged 60 to 79 years, 65.4% were pathological stage pT3, and 90.8% had no nodal involvement (N0). Two-thirds of the patients were eligible for cisplatin-based therapy, according to their GFRs.

The primary endpoint, DFS, of the surveillance arm was significantly increased by chemotherapy (hazard ratio [HR], 0.49; P = .001). More patients on chemotherapy were event free at 2 years (54% vs 71%). These DFS benefits were similar across various subgroup analyses.

The secondary endpoint, MFS, paralleled the benefits of chemotherapy (HR, 0.49; P = .002; event free at 2 years, 60% vs 74%). Furthermore, although the overall survival data remain to be reached, the researchers noted a similar trend in favour of chemotherapy (HR, 0.55).

The safety analysis indicated more adverse events in the chemotherapy group, illustrated by grade ≥3 toxicities, than in the surveillance group (53.2% vs 13.5%, respectively). However, no difference was evident at 12 and 24 months.

According to the protocol-defined early stopping rule, this study was closed to recruitment early.

“Based on these results, adjuvant platinum-based chemotherapy should be considered a new standard of care [in patients with UTUC],” concluded Dr. Birtle.

[Presentation title: Results of POUT - a Phase III Randomised Trial of Peri-Operative Chemotherapy Versus Surveillance in Upper Tract Urothelial Cancer (UTUC). Abstract 1017]

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