Atsushi Hiraoka1, Takashi Kumada2, Toshifumi Tada3, Masashi Hirooka4, Kazuya Kariyama5, Joji Tani6, Masanori Atsukawa7, Koichi Takaguchi8, Ei Itobayashi9, Shinya Fukunishi10, Kunihiko Tsuji11, Toru Ishikawa12, Kazuto Tajiri13, Hironori Ochi14, Satoshi Yasuda15, Hidenori Toyoda15, Chikara Ogawa16, Takashi Nishimura17, Takeshi Hatanaka18, Satoru Kakizaki19, Noritomo Shimada20, Kazuhito Kawata21, Atsushi Naganuma22, Hisashi Kosaka23, Hiroshi Shibata24, Tomoko Aoki25, Takaaki Tanaka1, Hideko Ohama1,10, Kazuhiro Nouso5, Asahiro Morishita6, Akemi Tsutsui8, Takuya Nagano8, Norio Itokawa7, Tomomi Okubo7, Taeang Arai7, Michitaka Imai12, Yohei Koizumi4, Shinichiro Nakamura3, Kouji Joko14, Hiroko Iijima17, Masaki Kaibori23, Yoichi Hiasa4, Masatoshi Kudo25. 1. Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan. 2. Department of Nursing, Gifu Kyoritsu University, Ogaki, Japan. 3. Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan. 4. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Japan. 5. Department of Gastroenterology, Okayama City Hospital, Okayama, Japan. 6. Department of Gastroenterology and Hepatology, Kagawa University, Kagawa, Japan. 7. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan. 8. Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan. 9. Department of Gastroenterology, Asahi General Hospital, Asahi, Japan. 10. Department of Gastroenterology, Osaka Medical and Phamaceutical University, Osaka, Japan. 11. Center of Gastroenterology, Teine Keijinkai Hospital, Sapporo, Japan. 12. Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan. 13. Department of Gastroenterology, Toyama University Hospital, Toyama, Japan. 14. Hepato-Biliary Center, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan. 15. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan. 16. Department of Gastroenterology, Japanese Red Cross Takamatsu Hospital, Takamatsu, Japan. 17. Department of Gastroenterology and Hepatology, Hyogo College of Medicine, Hyogo, Japan. 18. Department of Gastroenterology, Gunma Saiseikai Maebashi Hospital, Gunma, Japan. 19. Department of Clinical Research, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan. 20. Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan. 21. Hepatology Division, Department of Internal Medicine II, Hamamatsu University School of Medicine, Hamamatsu, Japan. 22. Department of Gastroenterology, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan. 23. Department of Surgery, Kansai Medical University, Hirakata, Japan. 24. Department of Gastroenterology, Tokushima Prefectural Central Hospital, Tokushima, Japan. 25. Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan.
Abstract
BACKGROUND/AIM: A comparison of therapeutic efficacy between atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib treatment given as first-line therapy for unresectable hepatocellular carcinoma (u-HCC) in regard to progression-free survival (PFS) overall survival (OS) has not been reported. We aimed to elucidate which of those given as initial treatment for u-HCC has greater prognostic impact on PFS and OS of affected patients, retrospectively. MATERIALS/ METHODS: From 2020 to January 2022, 251 u-HCC (Child-Pugh A, ECOG PS 0/1, BCLC-B/C) treated were enrolled (Atez/Bev-group, n = 194; lenvatinib-group, n = 57). PFS and OS were analyzed following adjustment based on inverse probability weighting (IPW). RESULTS: There was a greater number of patients with macro-vascular invasion in Atez/Bev-group (22.7% vs. 8.8%, p = 0.022). In lenvatinib-group, the frequencies of appetite loss (38.6% vs. 19.6%, p = 0.002), hypothyroidism (21.1% vs. 6.7%, p = 0.004), hand foot skin reaction (19.3% vs. 1.0%, p < 0.001), and diarrhea (10.5% vs. 4.6%, p = 0.012) were greater, while that of general fatigue was lower (22.8% vs. 26.3%, p = 0.008). Comparisons of therapeutic best response using modified response evaluation criteria in solid tumors (mRECIST) did not show significant differences between the present groups (Atez/Bev vs. lenvatinib: CR/PR/SD/PD = 6.1%/39.1%/39.1%/15.6% vs. 0%/48.0%/38.0%/14.0%, p = 0.285). In patients of discontinuation of treatments, 48.2% switched to lenvatinib, 10.6% continued beyond PD, 8.2% received another systemic treatment, 5.9% underwent transcatheter arterial chemoembolization (TACE), 3.5% received hepatic arterial infusion chemotherapy (HAIC), and 1.2% underwent surgical resection in Atez/Bev-group, while 42.2% switched to Atez/Bev, 4.4% continued beyond PD, 4.4% received another systemic treatment, 2.2% nivolumab, 6.7% received TACE, and 2.2% received HAIC in lenvatinib-group. Following adjustment with inverse probability weighting (IPW), Atez/Bev-group showed better PFS (0.5-/1-/1.5-years: 56.6%/31.6%/non-estimable vs. 48.6%/20.4%/11.2%, p < 0.0001) and OS rates (0.5-/1-/1.5-years: 89.6%/67.2%/58.1% vs. 77.8%/66.2%/52.7%, p = 0.002). CONCLUSION: The present study showed that u-HCC patients who received Atez/Bev as a first-line treatment may have a better prognosis than those who received lenvatinib.
BACKGROUND/AIM: A comparison of therapeutic efficacy between atezolizumab plus bevacizumab (Atez/Bev) and lenvatinib treatment given as first-line therapy for unresectable hepatocellular carcinoma (u-HCC) in regard to progression-free survival (PFS) overall survival (OS) has not been reported. We aimed to elucidate which of those given as initial treatment for u-HCC has greater prognostic impact on PFS and OS of affected patients, retrospectively. MATERIALS/ METHODS: From 2020 to January 2022, 251 u-HCC (Child-Pugh A, ECOG PS 0/1, BCLC-B/C) treated were enrolled (Atez/Bev-group, n = 194; lenvatinib-group, n = 57). PFS and OS were analyzed following adjustment based on inverse probability weighting (IPW). RESULTS: There was a greater number of patients with macro-vascular invasion in Atez/Bev-group (22.7% vs. 8.8%, p = 0.022). In lenvatinib-group, the frequencies of appetite loss (38.6% vs. 19.6%, p = 0.002), hypothyroidism (21.1% vs. 6.7%, p = 0.004), hand foot skin reaction (19.3% vs. 1.0%, p < 0.001), and diarrhea (10.5% vs. 4.6%, p = 0.012) were greater, while that of general fatigue was lower (22.8% vs. 26.3%, p = 0.008). Comparisons of therapeutic best response using modified response evaluation criteria in solid tumors (mRECIST) did not show significant differences between the present groups (Atez/Bev vs. lenvatinib: CR/PR/SD/PD = 6.1%/39.1%/39.1%/15.6% vs. 0%/48.0%/38.0%/14.0%, p = 0.285). In patients of discontinuation of treatments, 48.2% switched to lenvatinib, 10.6% continued beyond PD, 8.2% received another systemic treatment, 5.9% underwent transcatheter arterial chemoembolization (TACE), 3.5% received hepatic arterial infusion chemotherapy (HAIC), and 1.2% underwent surgical resection in Atez/Bev-group, while 42.2% switched to Atez/Bev, 4.4% continued beyond PD, 4.4% received another systemic treatment, 2.2% nivolumab, 6.7% received TACE, and 2.2% received HAIC in lenvatinib-group. Following adjustment with inverse probability weighting (IPW), Atez/Bev-group showed better PFS (0.5-/1-/1.5-years: 56.6%/31.6%/non-estimable vs. 48.6%/20.4%/11.2%, p < 0.0001) and OS rates (0.5-/1-/1.5-years: 89.6%/67.2%/58.1% vs. 77.8%/66.2%/52.7%, p = 0.002). CONCLUSION: The present study showed that u-HCC patients who received Atez/Bev as a first-line treatment may have a better prognosis than those who received lenvatinib.