Results of POUT: A phase III randomised trial of perioperative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC).

• DOI: 10.1200/jco.2018.36.6_suppl.407
• Publication Date: 2018-02-26T16:14:10Z
• Authors: Alison Jane Birtle; John David Chester; Robert Jones Jones; Mark Johnson; Michaela Hill; Richard T Bryan; James Catto; Jenny Donovan; Ann French; Chris Harris; Francis Keeley; Roger Kockelbergh; Thomas Powles; Rachel Todd; Lucy Tregellas; Caroline Wilson; Andrew Winterbottom; Rebecca Lewis; Emma Hall
• Keywords: Carboplatin; Urothelial cancer; Interim analysis; Clinical endpoint; Progression-free survival

407 Background: The role of post nephro-ureterectomy (NU) treatment for UTUC is unclear. POUT (CRUK/11/027; NCT01993979) addresses whether adjuvant chemotherapy improves disease free survival (DFS) pts with histologically confirmed pT2-T4 N0-3 M0 UTUC. Methods: Pts (max n = 345) ≤90 days NU were randomised (1:1) to 4 cycles gemcitabine-cisplatin (gemcitabine-carboplatin if GFR 30-49ml/min) or surveillance subsequent required. had 6 monthly cross sectional imaging and cystoscopy the first 2 years, then annually 5 years. Toxicity was assessed by CTCAE v4. Primary endpoint DFS. trial powered detect a hazard ratio (HR) 0.65 (i.e. improvement in 3 year DFS from 40% 55%; 2-sided alpha 5%, 80% power) Peto-Haybittle (p < 0.001) early stopping rules efficacy & inefficacy. Secondary endpoints included metastasis-free (PFS), overall (OS), toxicity quality life. Results: Between May 2012 Sept 2017, 248 recruited (123 surveillance; 125 chemotherapy) at 57 UK centres. In Oct independent oversight committees recommended close recruitment as data collected thus far (data snapshot 05/09/2017) met rule efficacy. At time interim analysis, median follow-up 17.6 months (IQR 7.5-33.6). age 69 years (range 36-88), 30% pT2, 65% pT3; 91% pN0;. Grade ≥3 toxicities reported 60% 24% pts. 47/123 (surveillance) 29/125 (chemotherapy) events reported; unadjusted HR 0.47 (95% CI: 0.29, 0.74) favour (log-rank p 0.0009). Two 51% 39, 61) 70% 58, 79). PFS favoured chemotherapy: 0.49 0.30, 0.79, 0.003). Conclusions: Adjuvant improved largest this pt population; terminated because favouring arm. Whilst follow up OS continues, should be considered new standard care these patients. Clinical information: ISRCTN98387754.