Third-line chemotherapy in advanced biliary cancers (ABC): pattern of care, treatment outcome and prognostic factors from a multicenter study

ABSTRACT

Objectives

Here, we aim at describing the pattern of care, survival outcome and prognostic factors of ABC patients (pts) receiving third-line chemotherapy.

Methods

Institutional registries across three academic medical centers were retrospectively reviewed. Kaplan–Meier estimators were used to calculate survival, the log-rank test to make comparisons, and the Cox proportional hazard models to assess the progostic impact of variables.

Results

Among 101 pts included in the analysis. 68 (67.3%), 19 (18.8%) and 14 (13.8%) had intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer, respectively. Atotal of 63 (62.3%) pts received monochemotherapy, while 38 (37.6%) were treated with adoublet. The median OS and PFS were 5 and 3 months, respectively. Disease control rate was achieved in 23 (22.7%) pts, with 2 (2%) partial responses. Grade 3–4 treatment-related adverse events were reported in 22 (21.7%) pts. At multivariate analysis, ECOG PS (p < 0.001), tumor burden (p = 0.01) and lymphocyte-to-monocyte ratio (p =0.02) were independent predictors of survival.

Conclusions

Third-line chemotherapy displayed limited activity in this real-world cohort, although prognostic factors have been identified that may assist in treatment decision. The results of this multicenter experience, highlight the need for more effective therapies and provide a benchmark for future trials in this setting.

KEYWORDS:

• Biliary cancer
• cholangiocarcinoma
• gallbladder cancer
• chemotherapy
• third-line
• prognosis
• survival
• real world

Declarations of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Acknowledgement

P.C. is a current recipient of a Marie Skłodowska-Curie Career Re-Integration fellowship funded by AIRC and the European Union’s Horizon 2020 research and innovation programme (Grant agreement No 800924). P.C. research activity is also funded by following grants: ”Fighting Cancer resistance: Multidisciplinary integrated Platform for a technological Innvovative Approach to Oncotherapies” and ”From Genomic to Therapy of Rare Tumours” (POR CAMPANIA FESR 2014/2020 ASSE I).

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

M Salati: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Resources; Software; Validation; Visualization; Writing – original draft; Writing – review & editing. A Rizzo: Data curation; Formal analysis; Investigation; Methodology; Visualization; Writing – original draft. V Merz: Data curation, Methodology, Writing – review & editing. C Messina: Data curation, Methodology, Writing – review & editing. F Caputo: Data curation; Formal analysis, Writing – original draft. F Gelsomino: Investigation, Methodology. A Spallanzani: Investigation, Methodology. AD Ricci: Data curation, Software, Resources. A Palloni: Data curation, Software, Resources. G Frega: Data curation, Software, Resources. S De Lorenzo: Formal analysis, Investigation; Methodology. P Carotenuto: Data curation, Methodology, Project administration. E Pettorelli: Data curation, Methodology, Project administration. S Benatti: Data curation, Methodology, Project administration. G Luppi: Supervision; Validation; Visualization; Writing – original draft; Writing – review & editing. D Melisi: Supervision; Validation; Visualization; Writing – original draft; Writing – review & editing. G Brandi: Supervision; Validation; Visualization; Writing – original draft; Writing – review & editing. M Dominici: Supervision; Validation; Visualization; Writing – original draft; Writing – review & editing.