Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response

Junho Kang, Jae Ho Jeong, Hee-Sang Hwang, Sang Soo Lee, Do Hyun Park, Dong Wook Oh, Tae Jun Song, Ki-Hun Kim, Shin Hwang, Dae Wook Hwang, Song Cheol Kim, Jin-Hong Park, Seung-Mo Hong, Kyu-Pyo Kim, Baek-Yeol Ryoo, Changhoon Yoo, Junho Kang, Jae Ho Jeong, Hee-Sang Hwang, Sang Soo Lee, Do Hyun Park, Dong Wook Oh, Tae Jun Song, Ki-Hun Kim, Shin Hwang, Dae Wook Hwang, Song Cheol Kim, Jin-Hong Park, Seung-Mo Hong, Kyu-Pyo Kim, Baek-Yeol Ryoo, Changhoon Yoo

Abstract

Purpose: The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated.

Materials and methods: In this prospective cohort study, programmed death ligand-1 (PD-L1)-positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks.

Results: Between May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or ≥ third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune- modified RECIST (imRECIST) and median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score ≥ 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049).

Conclusion: Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1-positive BTC patients. In patients who showed objective response, durable response could be achieved.

Keywords: Biliary tract cancer; Cholangiocarcinoma; Immunotherapy; Pembrolizumab.

Conflict of interest statement

Conflict of interest relevant to this article was not reported.

Figures

Fig. 1.
Fig. 1.
Waterfall plots of the changes in the size of target lesions.
Fig. 2.
Fig. 2.
Flow charts of a patient with pseudoprogression treated with pembrolizumab. Sum of target lesions and serum cancer antigen 19-9 (CA 19-9) levels are depicted with the computed tomography scan images. PD, progressive disease; CR, complete response.
Fig. 3.
Fig. 3.
Progression-free survival (according to Response Evaluation Criteria in Solid Tumor [RECIST] v1.1 and immune-modified RECIST [imRECIST]) and overall survival. OS, overall survival; CI, confidence interval; PFS, progression-free survival.
Fig. 4.
Fig. 4.
Progression-free survival (PFS) (A) and overall survival (OS) (B) according to the objective response graded based on immune-modified Response Evaluation Criteria in Solid Tumor. CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease; CI, confidence interval.
Fig. 5.
Fig. 5.
Progression-free survival (PFS) per immune-modified Response Evaluation Criteria in Solid Tumor and overall survival (OS) according to the tumor proportion score (TPS) of programmed death ligand-1. Cut-off at 1% (A, B), 20% (C, D), and 50% (E, F). CI, confidence interval.

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