PMID- 36971796 OWN - NLM STAT- MEDLINE DCOM- 20230731 LR - 20240416 IS - 1432-1335 (Electronic) IS - 0171-5216 (Linking) VI - 149 IP - 10 DP - 2023 Aug TI - Clinical outcomes of immune checkpoint inhibitors in unresectable or metastatic combined hepatocellular-cholangiocarcinoma. PG - 7547-7555 LID - 10.1007/s00432-023-04704-3 [doi] AB - 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. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Jang, Yoon Jung AU - Jang YJ AD - Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. AD - Department of Hematology/Oncology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea. FAU - Kim, Eo Jin AU - Kim EJ AD - Department of Hematology/Oncology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. FAU - Kim, Hyung-Don AU - Kim HD AD - Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. FAU - Kim, Kyu-Pyo AU - Kim KP AD - Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. FAU - Ryu, Min-Hee AU - Ryu MH AD - Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. FAU - Park, Sook Ryun AU - Park SR AD - Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. FAU - Choi, Won-Mook AU - Choi WM AD - Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Lee, Danbi AU - Lee D AD - Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Choi, Jonggi AU - Choi J AD - Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Shim, Ju Hyun AU - Shim JH AD - Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Kim, Kang Mo AU - Kim KM AD - Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Lim, Young-Suk AU - Lim YS AD - Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Lee, Han Chu AU - Lee HC AD - Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Ryoo, Baek-Yeol AU - Ryoo BY AD - Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. ryooby@amc.seoul.kr. FAU - Yoo, Changhoon AU - Yoo C AD - Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea. yooc@amc.seoul.kr. LA - eng PT - Journal Article DEP - 20230327 PL - Germany TA - J Cancer Res Clin Oncol JT - Journal of cancer research and clinical oncology JID - 7902060 RN - 0 (Immune Checkpoint Inhibitors) RN - 31YO63LBSN (Nivolumab) RN - 0 (Ipilimumab) RN - 2S9ZZM9Q9V (Bevacizumab) SB - IM MH - Male MH - Humans MH - Adult MH - Middle Aged MH - Aged MH - Aged, 80 and over MH - Female MH - Immune Checkpoint Inhibitors/adverse effects MH - Nivolumab/therapeutic use MH - *Carcinoma, Hepatocellular/drug therapy MH - Ipilimumab MH - Prospective Studies MH - Bevacizumab MH - Retrospective Studies MH - *Liver Neoplasms/drug therapy MH - *Cholangiocarcinoma/drug therapy MH - *Bile Duct Neoplasms/drug therapy MH - Bile Ducts, Intrahepatic OTO - NOTNLM OT - Chemotherapy OT - Combined hepatocellular-cholangiocarcinoma OT - Immune checkpoint inhibitor OT - Nivolumab OT - Pembrolizumab EDAT- 2023/03/28 06:00 MHDA- 2023/07/31 06:42 CRDT- 2023/03/27 11:13 PHST- 2023/02/05 00:00 [received] PHST- 2023/03/17 00:00 [accepted] PHST- 2023/07/31 06:42 [medline] PHST- 2023/03/28 06:00 [pubmed] PHST- 2023/03/27 11:13 [entrez] AID - 10.1007/s00432-023-04704-3 [pii] AID - 10.1007/s00432-023-04704-3 [doi] PST - ppublish SO - J Cancer Res Clin Oncol. 2023 Aug;149(10):7547-7555. doi: 10.1007/s00432-023-04704-3. Epub 2023 Mar 27.