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

POUT Investigators

Research output: Contribution to journalAbstractpeer-review

Abstract

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) for pts with histologically confirmed pT2-T4 N0-3 M0 UTUC. Methods: Pts (max n = 345) ≤90 days post NU were randomised (1:1) to 4 cycles of gemcitabine-cisplatin (gemcitabine-carboplatin if GFR 30-49ml/min) or surveillance with subsequent chemotherapy if required. Pts had 6 monthly cross sectional imaging and cystoscopy for the first 2 years, then annually to 5 years. Toxicity was assessed by CTCAE v4. Primary endpoint was DFS. The trial was powered to detect a hazard ratio (HR) of 0.65 (i.e. improvement in 3 year DFS from 40% to 55%; 2-sided alpha = 5%, 80% power) with Peto-Haybittle (p < 0.001) early stopping rules for efficacy & inefficacy. Secondary endpoints included metastasis-free survival (PFS), overall survival (OS), toxicity & quality of life. Results: Between May 2012 & Sept 2017, 248 pts were recruited (123 surveillance; 125 chemotherapy) at 57 UK centres. In Oct 2017, the independent trial oversight committees recommended POUT close to recruitment as data collected thus far (data snapshot 05/09/2017) met the early stopping rule for efficacy. At the time of interim analysis, median follow-up was 17.6 months (IQR 7.5-33.6). Pts had median age 69 years (range 36-88), 30% pT2, 65% pT3; 91% pN0;. Grade ≥3 toxicities were reported in 60% chemotherapy pts & 24% surveillance pts. 47/123 (surveillance) & 29/125 (chemotherapy) DFS events were reported; unadjusted HR = 0.47 (95% CI: 0.29, 0.74) in favour of chemotherapy (log-rank p = 0.0009). Two year DFS was 51% for surveillance (95% CI: 39, 61) and 70% for chemotherapy (95% CI: 58, 79). PFS favoured chemotherapy: HR = 0.49 (95% CI: 0.30, 0.79, p = 0.003). Conclusions: Adjuvant chemotherapy improved PFS in UTUC. POUT is the largest randomised trial in this pt population; the trial was terminated early because of efficacy favouring the chemotherapy arm. Whilst follow up for OS continues, this should be considered a new standard of care in these patients. Clinical trial information: ISRCTN98387754.
Original languageEnglish
Article numberAbstract 407
JournalJournal of Clinical Oncology
Volume36
Issue numberSuppl 6S
DOIs
Publication statusPublished - 9 Feb 2018
EventASCO Genitourinary Cancers Symposium 2018 - San Francisco, United States
Duration: 8 Feb 201810 Feb 2018

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  • Results of POUT - A phase III randomised trial of peri-operative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC)

    Alison Birtle (Plenary Speaker), Mark Johnson (Contributor), Roger Kockelbergh (Contributor), Frank Keeley (Contributor), Jim Catto (Contributor), Richard Bryan (Contributor), John Chester (Contributor), Robert Jones (Contributor), Micki Hill (Contributor), Jenny Donovan (Contributor), Ann French (Contributor), Chris Harris (Contributor), Thomas Powles (Contributor), Rachel Todd (Contributor), Lucy Tregellas (Contributor), Caroline Wilson (Contributor), Andrew WInterbottom (Contributor), Rebecca Lewis (Contributor) & Emma Hall (Contributor)

    19 Mar 2018

    Activity: Academic and Industrial eventsConference, workshop or symposium

  • Results of POUT - A phase III randomised trial of peri-operative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC)

    Alison Birtle (Plenary Speaker), Mark Johnson (Contributor), Roger Kockelbergh (Contributor), Frank Keeley (Contributor), Jim Catto (Contributor), Richard Bryan (Contributor), John Chester (Contributor), Robert Jones (Contributor), Micki Hill (Contributor), Jenny Donovan (Contributor), Ann French (Contributor), Chris Harris (Contributor), Thomas Powles (Contributor), Rachel Todd (Contributor), Lucy Tregellas (Contributor), Caroline Wilson (Contributor), Andrew WInterbottom (Contributor), Rebecca Lewis (Contributor) & Emma Hall (Contributor)

    9 Feb 2018

    Activity: Academic and Industrial eventsConference, workshop or symposium

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