Prognostic markers, quality of life (QoL) and value of health (V-He) in advanced biliary cancers (ABC) treated with second-line active symptom control (ASC) alone or ASC with oxaliplatin–5-FU chemotherapy (ASC + FOLFOX) in the randomised phase III, m

BACKGROUND: The ABC-06 trial established FOLFOX as the reference second-line regimen for patients diagnosed with advanced biliary tract cancer (ABC). Here we analysed the prognostic role of tumour markers carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and cancer antigen 125 (CA125) and the impact of FOLFOX on quality of life (QoL). PATIENTS AND METHODS: Patients diagnosed with ABC were randomly assigned (1:1) to second-line active symptom control (ASC) + modified FOLFOX or ASC alone. Tumour markers (CA19-9, CEA, and CA125) were measured and QoL (EORTC QLQ-C30, QLQ-BIL21) and value of health (EuroQol EQ-5D) questionnaires were completed at baseline and during follow-up. The prognostic value of baseline tumour markers, CA19-9 dynamics (week 4 change), time to deterioration of QoL (TTD; ≥10-point decline in global health status), and QoL changes over time (month 4 status) were assessed. RESULTS: Paired baseline and week 4 CA19-9 data were available for 37 patients in the ASC + FOLFOX arm. Stable/decreasing CA19-9 was associated with a numerically longer median radiological progression-free survival (PFS) and overall survival (OS; P values >0.05). Baseline CA19-9 data were available for 135 of 162 patients: 92 (68.1%) high, 43 (31.9%) low. High baseline CA19-9 was associated with shorter unadjusted OS [4.4 versus 6.4 months; hazard ratio (HR) 1.97, 95% confidence interval (CI) 1.33-2.93, P < 0.001] and unadjusted PFS (3.2 versus 5.0 months; HR 1.53, 95% CI 1.05-2.23, P = 0.027) in the FOLFOX arm. In 120 patients with baseline data for all markers available (CA19-9, CEA, and CA125), each marker independently predicted OS in the multivariable analysis: adjusted HR (aHR) 1.56 (95% CI 1.03-2.35, P = 0.003), aHR 1.60 (95% CI 1.06-2.43, P = 0.026), and aHR 1.70 (95% CI 1.13-2.56, P = 0.011) for CA19-9, CEA, and CA125, respectively. In addition, median OS decreased from 8.9 months (no markers elevated) to 3.2 months (all three elevated). QoL analysis (n = 76) showed no significant difference in TTD between arms (aHR 0.97, 95% CI 0.48-1.97, P = 0.94). FOLFOX did not worsen global, physical, social, or symptom QoL scores, whereas patients receiving ASC recorded declines across several domains. CONCLUSIONS: In the setting of second-line FOLFOX for ABC, elevated tumour markers impacted on prognosis and could be utilised as stratification factors in future clinical trials. The addition of FOLFOX did not imply QoL deterioration, and did, in fact, preserve some of the status in several domains.