The prognosis of first-line standard chemotherapy for advanced biliary tract cancers (BTCs) is still unsatisfactory. Based on phase Ⅲ trial TOPAZ-1, chemotherapy plus PD-L1 inhibitor had shown positive survival improvement. Other evidence showed that VEGF inhibitor could modify tumor immune-microenvironment while hepatic arterial infusion chemotherapy (HAIC) could improve the survival in cholangiocarcinoma. Combining these modalities may improve outcomes. Here we conducted a prospective study to evaluate the efficacy and safety of HAIC combined with bevacizumab (VEGF inhibitor) and toripalimab (PD-1 inhibitor) for advanced BTCs.
Patients with advanced untreated BTCs were recruited. The combination regimen was composed of hepatic arterial bevacizumab (300mg for 2h d1), followed by oxaliplatin (40 mg/m2 for 2h, days 1-3) and 5-fluorouracil (800 mg/m2 for 22h, days 1-3), with intravenous toripalimab (240 mg) on day 1 prior to HAIC, every 4 weeks. A maximum of six consecutive HAIC cycles. Then toripalimab (240mg) and bevacizumab (300mg) were intravenously infused every four weeks as maintenance treatment. The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate(ORR), which was evaluated according to imRECIST, progression-free survival (PFS), and safety.
Between 10/2019-12/2021, 32 patients were enrolled. The median follow-up time was 15.3 months. The ORR was 81.3%, and the disease control rate (DCR) was 96.9%. Median PFS, and OS were not reached. Six-month PFS rate and OS rate were 78.5% and 89.9%, respectively. The most frequent Grade 3/4 treatment-related adverse event was liver dysfunction (18.8%). Table: 60P
|Baseline characteristic, response, AEs|
|Median age (range), y||63(41−76)|
|6-m PFS (95% CI), %||78.5 (58.1−89.7)|
|6-m OS (95% CI), %||89.9 (71.9−95.7)|
|Grade 3/4 AEs, n (%)||10(31.3)|
These promising results may contribute to a paradigm shift in the first-line treatment for advanced BTC patients. Follow up for survival is ongoing.
Clinical trial identification
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Has not received any funding.
All authors have declared no conflicts of interest.