Capecitabine and streptozocin ± cisplatin for gastroenteropancreatic neuroendocrine tumours: predictors of long-term survival in the NET01 trial


Year:

Session type:

Theme:

Pippa Corrie1,Tim Meyer2,Wendi Qian3,Juan Valle4,Denis Talbot5,David Cunningham6,Nicholas Reed7,Lucy Wall8,Justin Waters9,Paul Ross10,Alan Anthoney11,Kate Sumpter12,Naveed Sarwar13,Tom Crosby14,Nazma Begum3,Gemma Young3,Richard Hardy3
1Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0QQ,2Royal Free Hospital, London NHS Foundation Trust, Pond Street, London, NW3 2QG,3Cambridge Cancer Trials Centre | Cambridge Clinical Trials Unit – Cancer Theme, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Hills Road, Cambridge, CB2 0QQ,4Department of Medical Oncology, University of Manchester, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX,5Department of Oncology, Oxford University Hospitals Trust, Churchill Hospital, Oxford, OX3 7LE,6Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT,7Beatson Oncology Centre, Gartnavel General Hospital, 1053 Great Western Road, Glasgow, G12 0YN,8Edinburgh Cancer Centre, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU,9Kent Oncology Centre, Maidstone Hospital, Hermitage Lane, Maidstone, ME16 9QQ,10Guy's & St Thomas' NHS Foundation Trust, Great Maze Pond, London, SE1 9RT,11St James's Institute of Oncology, St James’s University Hospital, Beckett Street, Leeds, LS9 7TF,12Northern Centre for Cancer Care, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle upon Tyne, NE7 7DN,13Southend University Hospitals NHS Foundation Trust, Prittlewell Chase, Westcliff-on-Sea, Essex, SS0 0RY,14Velindre Cancer Centre, Velindre NHS Trust, Velindre Place, Cardiff, CF14 2TL

Abstract

Background

Cytotoxic chemotherapy for advanced, unresectable pancreatic and gastrointestinal foregut neuroendocrine tumours (GEPNETs) commonly comprises 5-fluorouracil (FU) plus streptozocin (S). The NET01 trial, conducted in the pre-kinase inhibitor era, recruited a broad spectrum of patients to investigate whether capecitabine (Cap) was an acceptable alternative to FU, ± cisplatin (Cis).  At median follow-up 3.4 years, objective responses (primary endpoint) were reported as similar in the 2 arms, but CapSCis was more toxic. Final progression-free survival (PFS), overall survival (OS) (secondary endpoints) and OS predictors are now reported with longer follow up.  

Method

Patients with previously untreated advanced, unresectable NETs of pancreatic, gastrointestinal foregut or unknown primary site were randomised to receive three-weekly Cap 625mg/m2 twice daily orally, S 1·0g/m2 IV on day 1, ± Cis 70mg/m2 IV on day 1. All patients were followed 12 weekly for a minimum of 5 years.

Results

Of 86 (44 CapS, 42 CapSCis) patients randomised, 16% had poorly differentiated histology. With long-term median follow-up of 8 years, 83 (97%) patients have progressed/died and 69 (80%) patients have died. The estimated median PFS was 11.1 months for CapS and 9·6 months for CapSCis (HR=0.82, 95%CI: 0.53-.27). Median OS was 27 months for CapS and 26 months for CapSCis (HR=0.97, 95%CI: 0.60-1.56). Three and 5-year OS rates were 40% and 29%, with no difference between arms. Statistically significant factors predicting for OS were tumour Ki67 level, WHO grade and age. Addition of Cis to CapS did not appear to influence OS for high grade, poorly differentiated tumours, although numbers are small.

Conclusion

PFS and OS were similar for the CapS±Cis regimens. High patient age, tumour Ki67 and grade all predicted for poorer outcomes.