1139PD - Clinical outcomes from the UK CUP-ONE Study: A multi-centre trial to assess the efficacy of epirubicin, cisplatin and capecitabine (ECX) in carcino...

Date 29 September 2014
Event ESMO 2014
Session Neuroendocrine & endocrine tumours and CUP
Topics Anti-Cancer Agents & Biologic Therapy
Carcinoma of Unknown Primary Site
Translational Research
Presenter Harpreet Wasan
Citation Annals of Oncology (2014) 25 (suppl_4): iv394-iv405. 10.1093/annonc/mdu345
Authors H. Wasan1, J. Paul2, M.C. Nicolson3, T.R..J. Evans4, L. McMahon2, A. Morris2, E. McCartney2, C. Bridgewater5, D. Bowtell6, M. Erlander7, K.A. Oien8
  • 1Hammersmith Hospital, Department of Oncology, W12 0HS - London/GB
  • 2Cruk Clinical Trials Unit, Beatson Woscc, University of Glasgow, G12 0YN - Glasgow/GB
  • 3Medical Oncology, Aberdeen Royal Infirmary, GB-AB25 2ZN - Aberdeen/GB
  • 4Beatson Institute For Cancer Research, University of GlasgowBeatson Institute for Cancer Research, GB-G61 1BD - Bearsden, Glasgow/GB
  • 5Department Of Clinical Oncology, Weston Park Hospital, Sheffield, Sheffield/GB
  • 6Cancer Geonomics And Genetics Program, Peter MacCallum Cancer Centre, Melbourne/AU
  • 7Chief Scientific Officer, bioTheranostics Inc, San Diego/US
  • 8University Of Glasgow, Garscube Estate, Switchback Road, Cancer Research UK Beatson Laboratories, G61 1BD - Glasgow, Scotland/GB

Abstract

Aim

A multi-centre single-arm phase II trial of epirubicin, cisplatin and capecitabine (ECX) to establish the efficacy of the ECX regimen, and an associated translational study incorporating the prospective validation of molecular classifiers and exploratory metabonomics.

Methods

CUP-ONE combines a multicentre phase II trial of epirubicin, cisplatin and capecitabine (ECX) [Part 2] and a concurrent translational study [Part 1] incorporating blinded prospective validation of 3 diagnostic molecular classifiers. 'Good' CUP subsets are specifically excluded (i.e. mid-line tumours, germ-cell origin, isolated axillary or neck lymphodenopathy and neuroendocrine). Part 2 assessed treatment outcomes to evaluate, after exclusion of the 'best' CUP subsets, ECX was a valuable treatment. This was formally assessed by overall RECIST response rate (ORR) using a Simon's two-stage minimax design to test the null hypothesis that the true ORR is <20% versus the alternative that it is >= 40% (95% power, 5% 1-sided). This required 57 patients. Secondary endpoints were progression- free survival (PFS), overall survival (OS) and quality of life (QoL).

Results

Since February 2010, CUP-ONE has recruited 531 patients to Part 1 (still open) and 59 to Part 2 (54 in both). Part 2 closed to recruitment in February 2013. Results are presented for 58 eligible patients. Demographics: Male 47%, female 53%. ECOG PS 0: 38%, 1: 62%. Median age: 63 (range 29- 78). 91% Stage IV, 5% Stage III. 81% adenocarcinoma, 5% squamous carcinoma, 50% poorly or undifferentiated pathology. Study therapy: 30% completed 8 cycles of ECX (median 5 cycles). Efficacy: The null hypothesis was rejected with an estimated ORR of 35% (90% CI 25%- 47%; CR 7%; PR 28%; SD 26%, PD 30%). Median PFS 6.9 months (80% CI 4.8, 7.8), median OS 10.2 months (80% CI 8.3, 11.1). Treatment toxicities were acceptable with 54% recording worst AE grade <3.

Conclusions

CUP-ONE is the largest prospective CUP trial incorporating detailed diagnostic biomarkers including gene expression profiling. After excluding 'best' prognosis CUP patients, ECX proved an active and well- tolerated regimen. Correlation with translational outputs and QoL analysis is ongoing.

Disclosure

All authors have declared no conflicts of interest.