Tislelizumab plus GemOx and Lenvatinib as a Conversion Therapy Regimen for Potentially Resectable BTCs

Although biliary tract cancer (BTC) can only be cured by surgery, this is not an option for all patients. Converting locally unresectable patients to resectable status with conversion therapy can improve overall survival. One potential conversion therapy regimen includes tislelizumab, an anti–PD-1 monoclonal antibody. The combination of lenvatinib and tislelizumab has demonstrated encouraging antitumor and safety results in patients with advanced hepatocellular carcinoma. This study evaluated a potential role for a combination of lenvatinib, tislelizumab, and gemcitabine/oxaliplatin (GemOx) in potentially resectable BTC. Results were shared at the 2022 ESMO congress.

The combination of therapies was evaluated in a prospective, single-center, single-arm, phase 2 study. To be enrolled, patients had to have potentially resectable, locally advanced BTC and no previous systemic treatment. They also had to be Child-Pugh class A or B and have an ECOG performance status score of 0 or 1. Dosing was as follows: GemOx followed by intravenous tislelizumab (200 mg every 3 weeks) and lenvatinib (8 mg/kg orally daily) for ≤7 cycles. If at this point the cancer remained unresectable, patients continued to receive tislelizumab and lenvatinib.

The data reported here include evaluations of 25 patients. The median age of the patients was 59.7 years (range, 33-77 years); 44% of the patients were men. All patients had an ECOG performance status score of 1, and a large majority (92%) of the patients were Child-Pugh class A. The median tumor size was 5.3 cm (range, 1.57-11.036 cm); 36% of patients had intrahepatic metastases, 12% had extrahepatic metastases, and 60% had lymph node metastases.

The median duration of therapy before surgery was 3.44 cycles (range, 2-8 cycles). After treatment, 13 (52%) patients had received R0 resection, 2 (8%) patients received intraoperative radiotherapy, and 1 (4%) patient had complete pathological response. In terms of clinical/pathological outcomes, objective response rate was 56%, disease control rate was 92%, conversion rate was 84%, and surgery rate was 60%. Before treatment, 80% of patients had cancer antigen 19.9 levels >37 U/mL, and after treatment, this was reduced to 60% of patients.

No patients experienced severe complications. Grade 3 treatment-related adverse events included leukopenia, thrombocytopenia (3 patients each), diarrhea, and hypertension (2 patients each).

Based on these results, the authors concluded that the combination of tislelizumab with lenvatinib and GemOx is a promising therapeutic regimen for patients with potentially resectable locally advanced BTC.

Sources: Dongming L, Xihao Z, Han M, et al. A single-arm, open-label, phase II study of tislelizumab combined with lenvatinib and GEMOX regimen for conversion therapy of potentially resectable locally advanced biliary tract cancers. Ann Oncol. 2022;33(suppl 7):S570.

Dongming L, Xihao Z, Han M, et al. A single-arm, open-label, phase II study of tislelizumab combined with lenvatinib and GEMOX regimen for conversion therapy of potentially resectable locally advanced biliary tract cancers. European Society for Medical Oncology Congress 2022. Abstract 65P.