The randomized, open-label, multicenter, phase 3 ABC-06 trial established folinic acid/fluorouracil/oxaliplatin chemotherapy (FOLFOX) plus active symptom control (ASC) as the standard-of-care second-line treatment in patients with advanced biliary tract cancers (BTCs).1 A post-hoc analysis of the ABC-06 study explored the clinical relevance of tumor markers and chemotherapy-induced changes in patients with BTC after progression on gemcitabine/cisplatin (GemCis).
The ABC-06 study enrolled patients diagnosed with advanced BTCs, including cholangiocarcinomas, gallbladder cancer, or ampullary cancer, who had progressed after first-line GemCis. Eligible patients were randomly assigned 1:1 to receive FOLFOX plus ASC or ASC alone. Tumor markers (Ca19.9, CEA, and CA125) were assessed at baseline and every follow-up visit. The primary goal of the post-hoc analysis was to assess the association of Ca19.9 changes (stable/reducing vs increasing) at week 4 with radiologic progression-free survival (PFS). Secondary end points included correlation of raised baseline Ca19.9 (defined as 1.5 times the upper limit of normal) and chemotherapy-induced changes with overall survival (OS). A Cox regression model for OS was used to explore the prognostic roles of raised baseline Ca19.9, CEA, and CA125 that were adjusted for predefined stratification factors (platinum sensitivity, albumin, and disease stage) and treatment arm.
The ABC-06 study included 162 patients; 135 patients had baseline Ca19.9 data available. Among the 37 patients in the FOLFOX plus ASC arm with paired baseline and week 4 Ca19.9 data available, stable/reduced Ca19.9 was reported in 17 (45.9%) patients, and increasing Ca19.9 was seen in 20 (54.1%) patients.
A trend for numerically longer median radiologic PFS was seen in the patient cohort with stable/reducing Ca19.9 (4.3 months vs 3.3 months; hazard ratio [HR], 1.08; P = .81) and raised baseline Ca19.9 (5.7 months vs 3.2 months; HR, 1.68; P = .23); however, these differences were not significant. Raised baseline Ca19.9 was associated with significantly shorter unadjusted median PFS (3.2 months vs 5.0 months; HR, 1.53; P = .027) and unadjusted OS (4.4 months vs 6.4 months; HR, 1.97; P <.001). No significant impact of stable/reducing Ca19.9 on OS was seen at week 4 regardless of baseline Ca19.9 level (n = 37; P = .56) or in the context of raised baseline Ca19.9 (n = 23; P = .84).
The Cox regression model (n = 120) identified raised baseline Ca19.9 (HR, 1.56; P = .03), CEA (HR, 1.60; P = .026), and CA125 (HR, 1.70; P = .011) as independent prognostic factors. Unadjusted median OS was longer if all baseline tumor markers were not raised (8.9 months) compared with having 1 (7.0 months), 2 (4.0 months), or 3 (3.2 months) raised baseline tumor markers.
Based on these results, the authors concluded, “For ABC patients treated with second-line ASC plus FOLFOX, utility of Ca19.9 measured at week 4 after chemotherapy initiation is limited; raised baseline Ca19.9, CEA, and CA125 have independent prognostic roles, and future studies may need to consider these (individually or pooled) as stratification factors.”
Source: Lamarca A, Palmer DH, Wasan HS, et al. Clinical role of tumour markers in advanced biliary cancers (ABC) treated with second line active-symptom-control (ASC) alone or ASC with oxaliplatin/5-FU chemotherapy (ASC+mFOLFOX) in the randomised phase III, multi-centre, open-label ABC-06 trial. Abstract P-88.
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