ABC-06 | A randomised phase III study of Active Symptom Control (ASC) with/without mFOLFOX after progression to Cisplatin-Gemcitabine chemotherapy for patients with advanced biliary tract cancers


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Angela Lamarca1,Daniel H Palmer2,Harpreet Singh Wasan3,Paul J Ross4,Yuk Ting Ma5,Arvind Arora6,Stephen Falk7,Roopinder Gillmore8,Jonathan Wadsley9,Kinnari Patel10,Alan Anthoney11,Anthony Maraveyas12,Tim Iveson13,Justin S Waters14,Claire Blesing10,Safia Barber15,David Ryder15,John Ramage16,Linda Davies17,John A. Bridgewater18,Juan W Valle19
1The Christie NHS Foundation Trust, Manchester, UK,2University of Liverpool, Liverpool, UK,3Department of Cancer Medicine, Hammersmith Hospital, London, UK,4Guy's and St Thomas' NHS Foundation Trust, London, UK,5University of Birmingham, Birmingham, UK,6University Hospital of Nottingham NHS Trust, Nottingham, UK, University of Nottingham, Nottingham, UK,7Bristol Haematology and Oncology Centre, Bristol, UK,8Royal Free Hospital, London, UK,9Weston Park Hospital, Sheffield, UK,10Oxford University Hospitals, Oxford, UK,11Leeds Teaching Hospitals NHS Trust, Leeds, UK,12Castle Hill Hospital, Hull, UK,13University Hospital Southampton NHS Foundation Trust, Southampton, UK,14Kent Oncology Centre, Maidstone, UK,15Clinical Trials Unit, University of Manchester, Manchester, UK,16Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK,17Health Economics Department, University of Manchester, Manchester, UK,18University College London Cancer Institute, London, UK,19Institute of Cancer Sciences, University of Manchester, Manchester, UK, The Christie NHS Foundation Trust, Manchester, UK

Abstract

Background

Level A evidence supports use of Cisplatin-Gemcitabine as first-line chemotherapy for advanced biliary tract cancers (ABC); no robust evidence is available for second-line chemotherapy.

Method

Patients diagnosed with ABC with progression to first-line Cisplatin-Gemcitabine were randomised (1:1) to either ASC+mFOLFOX or ASC. Randomisation was stratified by serum albumin levels (<35 vs ≥35 g/L), platinum sensitivity (determined from first-line CisGem) and stage (locally advanced vs metastatic). Primary end-point was overall survival (OS) (multivariable Cox regression adjusted for stratification factors); sample size: 162 patients delivering 148 events were required (80% power; 5% two-sided alpha) for a hypothesised hazard ratio (HR) of 0.63. Assumed median survival for ASC was 4 months. Secondary end-points included progression-free survival (PFS) and response rate (ASC+mFOLFOX arm only).

Results

A total of 162 patients (81 in each arm) were randomised (27-March‘14–04-Jan‘18); median age 65 yrs (range 26-84); sex: 80 (49%) male, 82 (51%) female; primary site: intrahepatic 72 (44%), extrahepatic 45 (28%), gallbladder 34 (21%) and ampullary 11 (7%). Baseline characteristics were balanced between arms except platinum sensitivity (ASC+mFOLFOX 27 patients (33%); ASC 34 patients (42%)). After 150 OS events, the adjusted HR was 0.69 (95%CI 0.50-0.97; p=0.031; ASC+mFOLFOX vs ASC). Median OS (months (m)), 6m and 12m OS-rate (%) were 6.2m, 50.6% and 25.9% for the ASC+mFOLFOX and 5.3m, 35.5%, 11.4% for the ASC arm, respectively. Median PFS was 4.0 months (95%CI 3.2-5.0); response rate 5%, disease control rate 33%. Grade 3/4 toxicities were reported in 48 (59%) and 32 (39%) patients in the ASC+mFOLFOX and ASC arm, respectively; data cleaning is ongoing. Three chemotherapy-related deaths were reported.

Conclusion

Survival with ASC was greater than assumed; ASC+mFOLFOX improved OS after progression to CisGem with a clinically meaningful increase in 6m and 12m OS rate. ASC+mFOLFOX should become standard of care in second-line for ABC.

© 2019 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2019 ASCO Annual Meeting. All rights reserved.