ABC-06 | A randomised phase III, multi-centre, open-label study of active symptom control (ASC) alone or ASC with oxaliplatin / 5-FU chemotherapy (ASC+mFOLFOX) for patients (pts) with locally advanced / metastatic biliary tract cancers (ABC) previously-treated with cisplatin/gemcitabine (CisGem) chemotherapy

• Published in: Journal of clinical oncology Vol. 37; no. 15_suppl; p. 4003
• Main Authors: Lamarca, Angela, Palmer, Daniel H., Wasan, Harpreet Singh, Ross, Paul J., Ma, Yuk Ting, Arora, Arvind, Falk, Stephen, Gillmore, Roopinder, Wadsley, Jonathan, Patel, Kinnari, Anthoney, Alan, Maraveyas, Anthony, Waters, Justin S., Hobbs, Claire, Barber, Safia, Ryder, David, Ramage, John, Davies, Linda M, Bridgewater, John A., Valle, Juan W.
• Format: Journal Article
• Language: English
• Published: 20-05-2019
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2019.37.15_suppl.4003

Abstract only
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Background: Level A evidence supports use of CisGem as first-line chemotherapy for ABC; no robust evidence is available for second-line chemotherapy. Methods: Pts diagnosed with ABC with disease progression after prior CisGem 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 disease extent (locally advanced vs metastatic). Pts with ECOG PS0-1, adequate haematological, renal and liver function, and adequate biliary drainage were eligible. Primary end-point was overall survival (OS) (multivariable Cox regression adjusted for stratification factors); sample size: 162 pts 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. Results: 162 pts (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 pts (33%); ASC 34 pts (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. Grade 3/4 toxicities were reported in 48 (59%) and 32 (39%) pts in the ASC+mFOLFOX and ASC arm, respectively; these were balanced between arms except for fatigue and neutropenia (more frequent in ASC+mFOLFOX arm); data cleaning is ongoing. No 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. Clinical trial information: NCT01926236.