Pembrolizumab combined with lenvatinib as non-first-line therapy in patients with refractory biliary tract carcinoma

Abstract

Background: A therapeutic strategy involving combined treatment with lenvatinib plus pembrolizumab (LEP) has demonstrated a relatively high antitumor response in several solid tumors; however, the efficacy and safety of LEP in patients with refractory bile tract carcinoma (BTC) remains unknown.

Methods: This is a single-arm study for a preliminary assessment of the efficacy and tolerability of LEP in patients who experienced progression from prior systemic treatments. Pre-treatment tumor tissues were collected to retrospectively evaluate the expression status of PDL1.

Results: Thirty-two patients received second-line and above treatment with LEP. Overall, the objective response rate (ORR) was 25%, the disease control rate (DCR) was 78.1%, and the clinical benefit rate (CBR) was 40.5%. The median progression-free survival (PFS) was 4.9 months (95% CI: 4.7-5.2 months), and the median overall survival (OS) was 11.0 months (95% CI: 9.6-12.3 months). For tolerability, no grade 5 serious adverse events (AEs) were reported. All patients had any-grade AEs, and 59.3% of the patients experienced grade 3 AEs, while only 1 patient experienced a grade 4 AE of stomach bleeding. Fatigue was the most common AE, followed by hypertension and elevated aminotransferase levels. Retrospective analysis for PDL1 expression revealed that PDL1 positive tumor cells were associated with improved clinical benefits and survival outcomes.

Conclusions: LEP is a promising alternative as a non-first-line therapeutic regimen for patients with refractory BTC. Furthermore, well-designed prospective clinical trials with a control arm are still needed to obtain more evidences to confirm the efficacy and safety of this particular regimen as well as the role of PDL1 expression.

Keywords: PD1; PDL1; Pembrolizumab; bile tract cancer; lenvatinib.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/hbsn-20-338). Drs. YM, XS, and HZ serve as unpaid editorial board members of Hepatobiliary Surgery and Nutrition. SZ, WS and KW report personal fees of OrigiMed Co., Ltd, due to employments outside the submitted work. KW is a grant holder to this company. The other authors have no conflicts of interest to declare.

2020 Hepatobiliary Surgery and Nutrition. All rights reserved.

Figures

Figure 1

Therapeutic efficacy of lenvatinib combined with pembrolizumab (LEP) in patients with advanced biliary tract carcinoma. (A) Maximum percentage change in the sum of the diameters of the target lesions from baseline. The three different anatomical subtypes of biliary tract cancers are highlighted; (B) Kaplan-Meier estimation of progression-free survival of the entire cohort; (C) Kaplan-Meier estimation of overall survival of the entire cohort.

Figure 2

Association of the PDL1 expression detected by IHC staining with survival outcomes. (A) Subgroup analyses of progression-free survival (PFS) and overall survival (OS) in the entire population; (B) representative photomicrographs (40× objective) of PDL1 immunohistochemistry in patents’ archived pretreatment formalin-fixed and paraffin-embedded tumor tissue: negative PDL1 expression (no PDL1-stained tumor cell, B1; PDL1-stained tumor cell 5%, B3); (C) among the 32 patients with evaluable PD-L1 expression and available radiological assessments, the group with positive PDL1 expression (n=11) showed a prolonged progression-free survival compared with the group with negative PDL1 expression (n=21); (D) a significantly longer overall survival was observed in the group with positive PD-L1 expression. ECOG, Eastern Cooperative Oncology Group; HBV, hepatitis B virus; HR, hazard ratio.