Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study
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 nivoluma...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | JHEP Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589555923003221 |
| _version_ | 1797220547265822720 |
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| author | Bo Hyun Kim Hee Chul Park Tae Hyun Kim Young-Hwan Koh Jung Yong Hong Yuri Cho Dong Hyun Sinn Boram Park Joong-Won Park |
| author_facet | Bo Hyun Kim Hee Chul Park Tae Hyun Kim Young-Hwan Koh Jung Yong Hong Yuri Cho Dong Hyun Sinn Boram Park Joong-Won Park |
| author_sort | Bo Hyun Kim |
| collection | DOAJ |
| description | 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. ClinicalTrials.gov identifier: NCT04611165 |
| first_indexed | 2024-03-07T16:53:12Z |
| format | Article |
| id | doaj.art-8f31677ff257430f8b7f01273edc0299 |
| institution | Directory Open Access Journal |
| issn | 2589-5559 |
| language | English |
| last_indexed | 2024-04-24T12:51:16Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JHEP Reports |
| spelling | doaj.art-8f31677ff257430f8b7f01273edc02992024-04-06T04:40:21ZengElsevierJHEP Reports2589-55592024-04-0164100991Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II studyBo Hyun Kim0Hee Chul Park1Tae Hyun Kim2Young-Hwan Koh3Jung Yong Hong4Yuri Cho5Dong Hyun Sinn6Boram Park7Joong-Won Park8Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of KoreaDepartment of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaCenter for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea; Center for Proton Therapy, National Cancer Center, Goyang, Republic of KoreaCenter for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea; Department of Radiology, National Cancer Center, Goyang, Republic of KoreaDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaCenter for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of KoreaDivision of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaBiomedical Statistics Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of KoreaCenter for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea; Corresponding author. Address: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Center for Liver and Pancreatobiliary Cancer, National Cancer Center, 323 Ilsan-ro Ilsandong-gu, Goyang, Gyeonggi-do 10408, Republic of Korea; Tel.: +82-31-920-1605, fax: +82-31-920-1520.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. ClinicalTrials.gov identifier: NCT04611165http://www.sciencedirect.com/science/article/pii/S2589555923003221hepatocellular carcinomanivolumabradiotherapycombination therapy |
| spellingShingle | Bo Hyun Kim Hee Chul Park Tae Hyun Kim Young-Hwan Koh Jung Yong Hong Yuri Cho Dong Hyun Sinn Boram Park Joong-Won Park Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study JHEP Reports hepatocellular carcinoma nivolumab radiotherapy combination therapy |
| title | Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study |
| title_full | Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study |
| title_fullStr | Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study |
| title_full_unstemmed | Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study |
| title_short | Concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion: A phase II study |
| title_sort | concurrent nivolumab and external beam radiation therapy for hepatocellular carcinoma with macrovascular invasion a phase ii study |
| topic | hepatocellular carcinoma nivolumab radiotherapy combination therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2589555923003221 |
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