Clinical outcomes of immune checkpoint inhibitors in unresectable or metastatic combined hepatocellular–cholangiocarcinoma

• Published in: Journal of cancer research and clinical oncology 2023-08, Vol.149 (10), p.7547-7555
• Main Authors: Jang, Yoon Jung, Kim, Eo Jin, Kim, Hyung-Don, Kim, Kyu-Pyo, Ryu, Min-Hee, Park, Sook Ryun, Choi, Won-Mook, Lee, Danbi, Choi, Jonggi, Shim, Ju Hyun, Kim, Kang Mo, Lim, Young-Suk, Lee, Han Chu, Ryoo, Baek-Yeol, Yoo, Changhoon
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Bevacizumab; Bile Duct Neoplasms - drug therapy; Bile Ducts, Intrahepatic; Cancer Research; Carcinoma, Hepatocellular - drug therapy; Cholangiocarcinoma; Cholangiocarcinoma - drug therapy; Clinical outcomes; Clinical trials; Female; Hematology; Hepatitis B; Hepatocellular carcinoma; hepatoma; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Internal Medicine; Ipilimumab; Liver cancer; liver function; Liver Neoplasms - drug therapy; Male; Medicine; Medicine & Public Health; Metastases; Metastasis; Middle Aged; Nivolumab - therapeutic use; Oncology; Pembrolizumab; Prospective Studies; Retrospective Studies; Solid tumors; Survival; therapeutics
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-023-04704-3

Purpose Immune checkpoint inhibitors (ICIs) have been demonstrated to be effective for unresectable or metastatic hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA) in prior prospective trials. However, the clinical outcomes of ICIs in patients with combined HCC–CCA (cHCC–CCA) have not been investigated. Accordingly, we retrospectively evaluated the effectiveness and safety of ICIs in patients with unresectable or metastatic cHCC–CCA. Methods Among 101 patients with histologically documented cHCC–CCA who received systemic therapy, 25 received ICIs between January 2015 and September 2021 and were included in the current analysis. Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were retrospectively evaluated. Results The median age was 64 years (range 38–83) and 84% ( n  = 21) of patients were males. Most patients had Child–Pugh A liver function ( n  = 22, 88%) and hepatitis B virus infection (17, 68%). Nivolumab ( n  = 17, 68%) was the most frequently used ICI, followed by pembrolizumab ( n  = 5, 20%), atezolizumab plus bevacizumab ( n  = 2, 8%), and ipilimumab plus nivolumab ( n  = 1, 4%). All patients, except one, had previously received systemic therapy; median two lines (1–5 lines) of systemic therapy were administered prior to ICIs. With a median follow-up duration of 20.1 months (95% CI 4.9–35.2 months), the median PFS was 3.5 months (95% CI 2.4–4.8 months), and the median OS was 8.3 months (95% CI 6.8–9.8 months). The ORR was 20.0% ( n  = 5, nivolumab for 2 patients, pembrolizumab for 1, atezolizumab plus bevacizumab for 1, and ipilimumab plus nivolumab for 1) and the duration of response was 11.6 months (95% CI 11.2–12.0 months). Conclusions ICIs displayed clinical anti-cancer effectiveness, aligning with the results of prior prospective studies for HCC or CCA. Further international studies are required to define the optimal strategies for managing unresectable or metastatic cHCC–CCA.