Chemo continues to benefit UTUC patients, updated POUT analysis shows
In an updated analysis of the phase III POUT* trial presented at ASCO GU 2021, peri-operative chemotherapy continued to improve disease-free survival (DFS) compared with surveillance in patients with upper tract urothelial cancer (UTUC).
In the initial POUT analysis, adjuvant chemotherapy improved DFS in this patient setting at a median follow-up of 30.3 months. [Lancet 2020;395:1268-1277]
This updated analysis evaluated 261 individuals (median age 69 years) who have undergone nephro-ureterectomy for invasive UTUC (pT2–pT4 and pN0–pN3 or pTany N+). In node-positive patients, all visible nodes must have been removed at the time of surgery and post-operative CT scans should be negative. Following which, participants were randomized 1:1 to receive four 21-day cycles of adjuvant gemcitabine-cisplatin chemotherapy (or gemcitabine-carboplatin if glomerular filtration rate is 30–49 mL/min) or surveillance with subsequent chemotherapy if necessary. Median follow-up was 49.2 months. [ASCO GU 2021, abstract 455]
At 5 years, a strong DFS benefit was observed in favour of chemotherapy over surveillance (63 percent vs 46 percent; adjusted hazard ratio [adjHR], 0.54, 95 percent confidence interval [CI], 0.36–0.79; p=0.002), after adjusting for planned chemotherapy type, nodal status, pathologic stage, and microscopic margin status.
Chemotherapy also conferred a significant metastasis-free survival (MFS) benefit compared with surveillance (63 percent vs 44 percent; adjHR, 0.55, 95 percent CI, 0.37–0.82; p=0.003).
There was also a reduction in the relative risk of death with chemotherapy vs surveillance (65 percent vs 57 percent; adjHR, 0.77, 95 percent CI, 0.50–1.17; p=0.21). While this did not meet statistical significance, the sample population should be taken into context, noted Dr Alison Birtle from the Lancashire Teaching Hospitals NHS Foundation Trust, Preston, UK, during her presentation.
“[T]he original survival analysis should have been on the entire sample population of 345 patients,” explained Birtle. “[However,] because we [have already] met the primary endpoint of DFS, this analysis [was] done on 261 patients. [Therefore,] it is going to be underpowered; [nonetheless,] there is still … improvement.”
Moreover, more patients in the surveillance arm received chemotherapy post-recurrence, compared with those who had already received adjuvant CT, she added.
Three-year DFS, MFS, and overall survival (OS) rates were also higher with chemotherapy vs surveillance (71 percent vs 50 percent [DFS], 72 percent vs 53 percent [MFS], and 79 percent vs 67 percent [OS]).
There was no evidence of long-term toxicities with chemotherapy. The most common grade ≥2 adverse events after 6 months were hypertension and lethargy (10 percent for both), followed by urinary tract infection (6 percent) and hearing loss (5 percent).
Albeit nonsignificant, patient-reported quality of life (QoL) also favoured chemotherapy over surveillance, as per the EORTC QLQ-C30** global health status/QoL at both 1 and 2 years (p=0.22 and p=0.20, respectively).
“[The current analysis] has shown the maintained benefit of adjuvant platinum-based chemotherapy on DFS, the primary endpoint of the study,” said Birtle. Together with the MFS and OS benefits and lack of long-term toxicities with additional follow-up, the updated findings “support platinum-based adjuvant chemotherapy as a recommended standard of care post-nephrectomy.”