Study details
Patients in POUT’s chemotherapy arm received four cycles of chemotherapy—gemcitabine-cisplatin if their GFR was 50 mL/min or higher, or gemcitabine-carboplatin if their GFR was 30-49 mL/min—starting within 90 days of nephro-ureterectomy.
Of note, approximately 40% of all patients in the trial were aged 70 years or older, including the 5% who were aged 80 years or older. “This is very reassuring for a study of adjuvant platinum-based chemotherapy,” Dr. Birtle commented. Fully 71.2% of the chemotherapy patients received all four planned cycles.
In an intention-to-treat analysis, risk of disease-free survival events (death from any cause, metastasis, or any ureteric or renal bed recurrence) was sharply reduced with chemotherapy versus surveillance (hazard ratio, 0.49; P=.001). The proportion of patients event free at 2 years was 71% in the chemotherapy group and 54% in the surveillance group. Benefit was generally similar across subgroups, and findings were much the same after adjustment for nodal involvement, microscopic margin status, and planned chemotherapy regimen (hazard ratio, 0.47; P=.001).
Risk of metastasis-free survival events was also sharply lower with chemotherapy (hazard ratio, 0.49; P=.002), with a proportion event free at 2 years of 74% in the chemotherapy group and 60% in the surveillance group. These findings were also much the same after adjustment for the above factors (hazard ratio, 0.47; P=.002).
Overall survival tended to be better with chemotherapy than with surveillance (hazard ratio, 0.55), but data are still immature for this endpoint.
The rate of grade 3 or worse adverse events during the treatment period was 53.2% with chemotherapy and 13.5% with surveillance; events with chemotherapy were as expected, with neutropenia, thrombocytopenia, and gastrointestinal events predominating. The rate of febrile neutropenia was 5.7% with gemcitabine-cisplatin and 7.8% with gemcitabine-carboplatin, but there were no neutropenic deaths.
The rate of grade 3 or worse adverse events for the entire trial period was 62.1% with chemotherapy and 24.8% with surveillance.
Data on nephrotoxicity are still being evaluated, according to Dr. Birtle. Only seven patients who started on gemcitabine-cisplatin had to switch to gemcitabine-carboplatin because their GFR fell.
In a related translational study, the investigators are evaluating both the baseline CT urograms and the resected tumors to identify prognostic and predictive markers, she said.
Dr. Birtle disclosed that she receives honoraria from Roche, Janssen, Astellas, and Bayer, and is a consultant to Sanofi-Aventis. The trial was funded by the UK Clinical Trials Awards and Advisory Committee.
SOURCE: Birtle A et al. Genitourinary Cancers Symposium. Abstract 407