GemOX plus immune checkpoint inhibitor in combination with lenvatinib or NGS-guided targeted therapy in patients with biliary tract cancers.

Abstract

e16133 Background: The combination of gemcitabine-based chemotherapy and immune checkpoint inhibitors has made great progress recently in advanced biliary tract cancer (BTC). Multi-target TKI lenvatinib or next-generation sequencing (NGS)-guided molecular targeted therapy are also promising. The aim of this study was to explore the anti-tumor effects of combined GemOX plus anti-PD-1 sintilimab and TKI either by lenvatinib or by NGS-guided targeted therapy if there is available target for local advanced or metastatic BTCs. Methods: This is a prospective single arm clinical study. Patients with local advanced or metastatic BTC were given intravenous infusion of standard GemOX (85mg/m2 oxaliplatin on day 1 and gemcitabine 1000mg/m2 on a 1-8-day schedule of a 3-week treatment cycle) plus 200mg q3w of sintilimab and lenvatinib or targeted therapy based on NGS (olaparib for BRCA1/2 mutation, dasatinib for IDH1/2 mutation, afatinib for EGFR mutation, lenvatinib for PDGFR and KIT mutation, lenvatinib for FGFR/KIT mutation). The primary end point was objective response rate (ORR), and the secondary end points were progression-free survival (PFS) and overall survival (OS). Tumor response was evaluated according to RECIST v1.1 criteria. Results: From November 2020 to December 2021, 22 patients with locally advanced or metastatic BTCs (6 GBC, 14 iCCA, 1 pCCA and 1 dCCA) were enrolled in the regimen, with an average age of 58.4 years. Partial response (PR) was achieved in 10 cases, stable disease (SD) in 9 cases and progression disease (PD) in 3 cases (13.6 %). The objective response rate (ORR) was 45.5%, and the disease control rate (DCR) was 86.4%. By December 31st, 2021, the median follow-up time was 13.1 months. The most common adverse events were anorexia (68.2%), nausea (68.2%), vomiting (36.36%), hair loss (45.5%) and bone marrow suppression (63.6%). During the treatment, the incidence of adverse reactions was 81.8%, and the incidence of grade 3/4 adverse events was 9.09%. For 14 patients with NGS, 5 patients were treated by targeting IDH2, EGFR, FGFR2, PDGFRA/KIT, BRCA2 and resulted in 1 SD and 4 PR with an ORR of 80% and DCR of 100%. The ORR and DCR were both 100% for 4 patients with programmed cell death ligand-1 (PD-L1) expression. While for the 3 patients with supper-progression markers such as RET, MDM2 and FGF14/STK24, there were 2 SD and 1 PD with an ORR of 0% and DCR of only 33%. Conclusions: In patients with advanced BTCs, the combination of GemOX plus sintilimab and lenvatinib or NGS-guided targeted therapy showed promising ORR and DCR, especially for the patients with positive PD-L1 expression and targetable gene alterations.