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
Session type: Clinical Trials Showcase
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.
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).
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.
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.