Abstract 288P
Background
Biliary tract cancers (BTCs) are aggressive malignancies with limited response to chemotherapy and a dismal prognosis. Gemcitabine/cisplatin (GC) was considered the first-line treatment option in advanced disease for many years until the success of two phase 3 trials (TOPAZ-01, KEYNOTE-966). Current guidelines recommend immune checkpoint inhibitors (ICIs) combined with chemotherapy as the standard of care. We aim to compare the efficacy of first-line therapies for advanced BTC.
Methods
Our search focused on English-language articles from MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, published between January 2010 and February 2024. We included full-text randomized clinical trials (RCTs) investigating GC as a treatment arm for treatment-naïve adult patients with advanced BTC. Outcomes measured were overall survival (OS) and progression-free survival (PFS). We conducted a one-stage meta-analysis using reconstructed patient-level survival data, employing Cox models and restricted mean survival time (RMST) to evaluate survival differences. A shared frailty model addressed study heterogeneity in a sensitivity analysis.
Results
6481 studies were screened and 14 RCTs selected. 4052 patients were included with 1951 (48%) receiving GC. The distribution of tumor location was 44% intrahepatic, 22% extrahepatic, 32% gallbladder and 2% ampullary cancers. Our meta-analysis compared 13 treatment arms. The combinations of G+S-1, GC+S-1, and GC+ICI showed improved OS and PFS over GC alone (Table). At 2.5 years follow-up, RMST for OS and PFS were significantly longer by 2.6, 2.8, 1.2 and 1.1, 2.1, 3.6 months in G+S-1, GC+S-1, GC+ICI arms. The frailty model revealed that only GC+S-1 significantly improved OS compared to GC (HR: 0.97, 95% CI: 0.94-0.99, p=0.049). Table: 288P
| RCT | Regimen | OS | PFS |
| Okusaka, Valle 10 | G | 1.04***1.02-1.05 | 1.02***1.01-1.03 |
| Kang 12 | C + S-1 | 1.03*1.00-1.05 | 1.021.00-1.05 |
| Sharma 19 | mGOx | 1.37**1.12-1.67 | 1.040.85-1.28 |
| Markussen 20 | GOxCap | 1.08*1.02-1.14 | 1.030.97-1.09 |
| Phelip 21 | mFOLFIRINOX | 10.98-1.03 | 10.98-1.02 |
| Valle 15 | GC + Cediranib | 0.970.81-1.07 | 0.950.87-1.03 |
| Vogel 18 | GC + Panitumumab | 0.930.89-1.07 | 0.940.82-1.08 |
| Valle 21 | GC + Merestinib | 0.960.93-1.00 | 0.970.93-1.01 |
| GC + Ramucirumab | 1.010.98-1.05 | 0.990.96-1.03 | |
| Doherty 22 | GC + Selumentinib | 10.96-1.05 | 0.990.95-1.03 |
| Morizane 19 | G + S-1 | 0.93*** 0.89-0.97 | 0.96* 0.92-0.99 |
| Ioka 23 | GC + S-1 | 0.97*** 0.95-0.99 | 0.97** 0.96-0.99 |
| Oh 22, Kelley 23 | GC + ICI | 0.99*** 0.98-0.99 | 0.99* 0.98-0.99 |
Conclusions
Adding ICI to chemotherapy offers only modest survival improvements, while including S-1 in GC significantly improves survival, indicating its potential value as a treatment option in BTC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R. Grant: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Knight Therapeutics; Financial Interests, Personal, Other, Graduate scholarship: Pfizer; Non-Financial Interests, Advisory Role: Tempus, Incyte. G.M. O'Kane: Financial Interests, Institutional, Research Grant: Roche, AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca, Servier, Incyte. A. Vogel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Mannheim, Eisai, Incyte, Ipsen, Janssen, MSD, Pierre Fabre, Roche, Servier, Tyra, Tahio; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Ipsen, Lilly, MSD, Roche, AstraZeneca, Roche, MSD, BeiGene, Jiangsu Hengrui Medicines. G. Sapisochin: Financial Interests, Personal, Advisory Board: AstraZeneca, Roche, HeparRegeniX; Financial Interests, Personal, Invited Speaker: AstraZeneca, Integra, Chiesi; Financial Interests, Personal, Other, Research study: Novartis; Financial Interests, Personal, Stocks/Shares: Amgen, CVS Health, Gilead, J&J, Merck, Pfizer, UnitedHealth; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Funding: Roche, Stryker. All other authors have declared no conflicts of interest.