PMID- 38344445 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240213 IS - 2235-1795 (Print) IS - 1664-5553 (Electronic) IS - 1664-5553 (Linking) VI - 13 IP - 1 DP - 2024 Feb TI - Thyroid Dysfunction after Atezolizumab and Bevacizumab Is Associated with Favorable Outcomes in Hepatocellular Carcinoma. PG - 89-98 LID - 10.1159/000531182 [doi] AB - INTRODUCTION: Atezolizumab and bevacizumab (Ate/Bev) combination has become the new first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). Although several studies reported thyroid dysfunction after treatment with immune checkpoint inhibitors, the clinical and immunological significance of thyroid dysfunction in patients treated with Ate/Bev has not been comprehensively addressed. We aimed to comprehensively evaluate the clinical and immunological implications of thyroid dysfunction in unresectable HCC patients treated with Ate/Bev. METHODS: We enrolled 208 patients with unresectable HCC treated with Ate/Bev from three Korean cancer centers. Thyroid adverse events (AEs) were reviewed, and cytokines and T cells in the blood samples were analyzed at baseline. For external validation, we analyzed clinical outcomes according to thyroid AEs in patients treated with Ate/Bev in the IMbrave150 study. RESULTS: Forty-one (19.7%) out of 208 patients experienced thyroid dysfunction (hypothyroidism [17.3%] and thyrotoxicosis [5.8%]) after Ate/Bev treatment. Median time to onset of hypothyroidism and thyrotoxicosis after Ate/Bev treatment was 3.5 and 1.3 months, respectively. Patients with thyroid AEs demonstrated significantly better progression-free survival, overall survival, and objective response rate than those without thyroid AEs. These findings were still consistent even after adjusting for confounding factors. Furthermore, favorable survival outcomes in patients with thyroid AEs were also validated in a cohort of IMbrave150 patients. While patients with thyrotoxicosis showed a significantly lower level of baseline IL-6, those with hypothyroidism did not show significant differences in circulating cytokine levels and CD8(+) T-cell fractions. CONCLUSIONS: A fraction of patients with HCC treated with Ate/Bev experienced thyroid dysfunction, and the development of thyroid AEs was associated with favorable clinical outcomes. CI - (c) 2023 The Author(s). Published by S. Karger AG, Basel. FAU - Song, Young Shin AU - Song YS AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea. AD - Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, South Korea. FAU - Yang, Hannah AU - Yang H AD - Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea. FAU - Kang, Beodeul AU - Kang B AD - Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea. FAU - Cheon, Jaekyung AU - Cheon J AD - Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea. FAU - Kim, Ilhwan AU - Kim I AD - Division of Oncology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea. FAU - Kim, Hyeyeong AU - Kim H AD - Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea. FAU - Lee, Won Suk AU - Lee WS AD - Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea. FAU - Sang, Yun Beom AU - Sang YB AD - Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea. FAU - Jung, Sanghoon AU - Jung S AD - Department of Radiology, CHA Bundang Medical Center, Seongnam, South Korea. FAU - Lim, Ho Yeong AU - Lim HY AD - Division of Hemato-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. FAU - Gaillard, Vincent E AU - Gaillard VE AD - F. Hoffmann-La Roche Ltd., Basel, Switzerland. FAU - Kim, Chan AU - Kim C AD - Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea. FAU - Chon, Hong Jae AU - Chon HJ AD - Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea. LA - eng PT - Journal Article DEP - 20230525 PL - Switzerland TA - Liver Cancer JT - Liver cancer JID - 101597993 PMC - PMC10857827 OTO - NOTNLM OT - Atezolizumab OT - Bevacizumab OT - Hepatocellular carcinoma OT - Thyroid adverse events COIS- Hong Jae Chon has a consulting or advisory role at Eisai, Roche, Bayer, ONO, MSD, BMS, Celgene, Sanofi, Servier, AstraZeneca, SillaJen, Menarini, and GreenCross Cell and has received research grants from Roche, Dong-A ST, and Boryung Pharmaceuticals. Chan Kim has a consulting or advisory role at Roche, ONO, MSD, BMS, Oncocross, and Virocure and has received research grants from Boryung Pharmaceuticals, Oncocross, SillaJen, and Virocure. Ho Yeong Lim has a consulting or advisory role at Eisai, Roche, Bayer, ONO, MSD, BMS, and AstraZeneca. Vincent E. Gaillard is a full-time employee of F. Hoffmann-La Roche Ltd. The other authors have no potential conflicts of interest to disclose. EDAT- 2024/02/12 15:42 MHDA- 2024/02/12 15:43 PMCR- 2024/02/01 CRDT- 2024/02/12 04:23 PHST- 2023/02/09 00:00 [received] PHST- 2023/05/18 00:00 [accepted] PHST- 2024/02/12 15:43 [medline] PHST- 2024/02/12 15:42 [pubmed] PHST- 2024/02/12 04:23 [entrez] PHST- 2024/02/01 00:00 [pmc-release] AID - 531182 [pii] AID - 10.1159/000531182 [doi] PST - epublish SO - Liver Cancer. 2023 May 25;13(1):89-98. doi: 10.1159/000531182. eCollection 2024 Feb.