PMID- 38463541 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240312 IS - 2589-5559 (Electronic) IS - 2589-5559 (Linking) VI - 6 IP - 4 DP - 2024 Apr TI - Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study. PG - 100991 LID - 10.1016/j.jhepr.2023.100991 [doi] LID - 100991 AB - BACKGROUND AND AIMS: Nivolumab was the first immune checkpoint inhibitor approved for hepatocellular carcinoma (HCC). External beam radiation therapy (EBRT) is locally effective and may enhance the effectiveness of immunotherapy. This study investigated the efficacy and safety of concurrent nivolumab and EBRT in HCC with macrovascular invasion. METHODS: In this phase II multicenter trial, patients with HCC and macrovascular invasion were concurrently treated with intravenous nivolumab (3 mg/kg every 2 weeks) and EBRT, followed by maintenance nivolumab until progression or unacceptable toxicity. Primary endpoints were progression-free survival (PFS) and safety, and secondary endpoints were overall survival, time-to-progression, objective response rate, and disease control rate. RESULTS: Between January 2020 and June 2021, 50 patients (male 84%, median age 62.5) were enrolled; 47 (94.0%) and 13 (26.0%) with portal (Vp1/2, n = 21; Vp3, n = 23; Vp4, n = 3) and hepatic vein invasion, respectively. Patients received EBRT (median dose: 50 [IQR 43-50] Gy) after the first nivolumab dose. The median number of nivolumab doses was 8.5. Median PFS was 5.6 (90% CI 3.6-9.9) months. Median overall survival and time-to-progression were 15.2 (90% CI 10.8-19.6) and 5.6 (90% CI 3.6-9.9) months, respectively. The objective response rate and disease control rate were 36.0% and 74.0%, respectively. The median duration of response was 9.9 months. Of 35 patients with follow-up data, 23 received subsequent systemic treatment, including atezolizumab-bevacizumab, sorafenib, lenvatinib, and regorafenib. Treatment-related any grade adverse events (AEs) and grade 3/4 AEs occurred in 40 (80.0%) and 6 (12.0%) patients, respectively. Common treatment-related AEs included pruritus (38.0%) and rash (16.0%), with no treatment-related deaths. CONCLUSION: Concurrent nivolumab therapy and EBRT showed encouraging PFS with acceptable safety in patients with advanced HCC and macrovascular invasion. IMPACT AND IMPLICATIONS: Immune checkpoint inhibitors, the standard care for advanced hepatocellular carcinoma (HCC), show relatively poor therapeutic effects in patients with advanced HCC and macrovascular invasion. In this investigator-initiated phase II study, we, for the first time, show that concurrent external beam radiation therapy with nivolumab, an immune checkpoint inhibitor, led to encouraging progression-free survival in patients with HCC and macrovascular invasion. The concurrent treatment was tolerable without significant safety concerns. Further randomized studies investigating the combination of immunotherapy and external beam radiation therapy are required. CLINICALTRIALSGOV IDENTIFIER: NCT04611165. CI - (c) 2023 The Authors. FAU - Kim, Bo Hyun AU - Kim BH AD - Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea. FAU - Park, Hee Chul AU - Park HC AD - Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. FAU - Kim, Tae Hyun AU - Kim TH AD - Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea. AD - Center for Proton Therapy, National Cancer Center, Goyang, Republic of Korea. FAU - Koh, Young-Hwan AU - Koh YH AD - Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea. AD - Department of Radiology, National Cancer Center, Goyang, Republic of Korea. FAU - Hong, Jung Yong AU - Hong JY AD - Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. FAU - Cho, Yuri AU - Cho Y AD - Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea. FAU - Sinn, Dong Hyun AU - Sinn DH AD - Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. FAU - Park, Boram AU - Park B AD - Biomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea. FAU - Park, Joong-Won AU - Park JW AD - Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea. LA - eng SI - ClinicalTrials.gov/NCT04611165 PT - Journal Article DEP - 20231221 PL - Netherlands TA - JHEP Rep JT - JHEP reports : innovation in hepatology JID - 101761237 PMC - PMC10920711 OTO - NOTNLM OT - combination therapy OT - hepatocellular carcinoma OT - nivolumab OT - radiotherapy COIS- J-WP has served in a consulting or advisory role for Roche, AstraZeneca, and Bigene; received honoraria from Roche, AstraZeneca, Bayer, and Eisai; and participated in the research sponsored by Ono, BMS; AstraZeneca; Roche; Eisai; Exelixis; Merk-MSD. BHK has served in an advisory role for Eisai and Roche, received honoraria from Eisai, Roche, and Hanmi, received a research grant from Hanmi, and participated in research sponsored by Ono-BMS. JYH has served as an advisory role for Eisai and AstraZeneca; received honoraria from Eisai, Dong-A, and Kyowa Kirin; and has participated in research sponsored by Roche, AstraZeneca, MSD, and Ono-BMS. HCP, THK, Y-HK, YC, DHS, and BP have no conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details. EDAT- 2024/03/11 06:42 MHDA- 2024/03/11 06:43 PMCR- 2023/12/21 CRDT- 2024/03/11 04:22 PHST- 2023/11/17 00:00 [received] PHST- 2023/12/09 00:00 [revised] PHST- 2023/12/13 00:00 [accepted] PHST- 2024/03/11 06:43 [medline] PHST- 2024/03/11 06:42 [pubmed] PHST- 2024/03/11 04:22 [entrez] PHST- 2023/12/21 00:00 [pmc-release] AID - S2589-5559(23)00322-1 [pii] AID - 100991 [pii] AID - 10.1016/j.jhepr.2023.100991 [doi] PST - epublish SO - JHEP Rep. 2023 Dec 21;6(4):100991. doi: 10.1016/j.jhepr.2023.100991. eCollection 2024 Apr.