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 plus mFOLFOX) in the randomised phase III, multi-centre, open-label ABC-06 trial
Lamarca, Angela Palmer, D. Wasan, H. Ross, P. Ma, Y. T. Arora, A. Falk, S. Gillmore, R. Wadsley, J. Patel, K.
Lamarca, Angela
Palmer, D.
Wasan, H.
Ross, P.
Ma, Y. T.
Arora, A.
Falk, S.
Gillmore, R.
Wadsley, J.
Patel, K.
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Abstract
Background: The ABC-06 clinical trial stablished ASC+mFOLFOX as the standard of
care treatment after Cisplatin and Gemcitabine (CisGem) for ABC.
Methods: Within the ABC-06 study, patients (pts) diagnosed with ABC (chol-
angiocarcinoma, gallbladder or ampullary cancer) with progression after CisGem were
randomised (1:1) to ASC+mFOLFOX or ASC. Tumour markers (CA19.9, CEA and CA125),
were scheduled at baseline (BSL) and at every follow-up visit. This post-hoc analysis
explored if changes (stable/reducing vs increasing) of Ca19.9 at week 4 from initiation
of ASC+mFOLFOX was associated with radiological progression-free survival (PFS).
Secondary end-points included impact of raised BSL Ca19.9 (defined as x1.5 ULN) and
chemotherapy-induced changes on overall survival (OS). CEA and CA125 were also
analysed.
Results: Out 162 pts randomised, BSL Ca19.9 data was available for 135 pts. Paired
BSL and week-4 Ca19.9 data was available for 37 pts in the ASC+mFOLFOX arm:
Ca19.9 was stable/reducing in 17 (45.9%) and increasing in 20 pts (54.1%). Stable/
reducing Ca19.9 showed a numerically longer median radiological PFS (4.3 months
(m) vs 3.3m) but differences did not reach statistical significance (HR 1.08 (95% CI
0.55-2.14); p¼0.81). When restricted to patients with raised BSL Ca19.9 (23 pts),
impact on PFS was more marked (5.7m vs 3.2m), but remained non-significant (HR
1.68 (95% CI 0.70-4.01); p¼0.23). Stable/reducing Ca19.9 at week 4 did not impact
significantly on OS (p¼0.56 (regardless of BSL Ca19.9 level; 37 pts); p¼0.84 (if raised
BSL Ca19.9; 23 pts)). Raised BSL Ca19.9 was associated both with shorter unadjusted
clinical median PFS (3.2m vs 5.0m; HR 1.53 (95% CI 1.05-2.23); p¼0.027) and un-
adjusted OS (4.4m vs 6.4m; HR 1.97 (95% CI 1.33-2.93); p When Cox Regression model
(120 pts) for OS exploring the prognostic roles of raised BSL Ca19.9, CEA and CA125
was adjusted for pre-defined stratification factors (platinum sensitivity, albumin, and
stage) and randomised trial arm, each raised tumour marker had an independent
impact (HR 1.56 (95% CI 1.03 to 2.35); p¼0.03 / HR 1.60 (95% CI 1,06 to 2.43)
p¼0.026 / HR 1.70 (95% CI 1.13 to 2.56); p¼0.011 for Ca19.9, CEA and CA125,
respectively). Unadjusted median OS was 8.9m if all tumour markers at BSL were non-
raised, and 7.0m, 4.0m, 3.2m in the event of having 1, 2 or 3 raised BSL tumour
markers.
Conclusions: For ABC patients treated with second-line ASC+mFOLFOX, utility of
Ca19.9 measured at week-4 after chemotherapy initiation is limited; raised BSL
Ca19.9, CEA and CA125 have independent prognostic roles and future studies may
need to consider these (individually or pooled) as stratification factors.
Description
Date
2022
Publisher
Collections
Keywords
Type
Meetings and Proceedings
Citation
Lamarca A, Palmer D, Wasan H, Ross P, Ma YT, Arora A, 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 plus mFOLFOX) in the randomised phase III, multi-centre, open-label ABC-06 trial. Annals of Oncology. 2022 Jun;33:S280-S. PubMed PMID: WOS:000823826500101.