Does first‐line treatment have prognostic impact for unresectable HCC?—Atezolizumab plus bevacizumab versus lenvatinib
Authors: Hiraoka Atsushi , Kumada Takashi , Tada Toshifumi , Hirooka Masashi , Kariyama Kazuya , Tani Joji , Atsukawa Masanori , Takaguchi Koichi , Itobayashi Ei , Fukunishi Shinya , Tsuji Kunihiko , Ishikawa Toru , Tajiri Kazuto , Ochi Hironori , Yasuda Satoshi , Toyoda Hidenori , Ogawa Chikara , Nishimura Takashi , Hatanaka Takeshi , Kakizaki Satoru , Shimada Noritomo , Kawata Kazuhito , Naganuma Atsushi , Kosaka Hisashi , Shibata Hiroshi , Aoki Tomoko , Tanaka Takaaki , Ohama Hideko , Nouso Kazuhiro , Morishita Asahiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Okubo Tomomi , Arai Taeang , Imai Michitaka , Koizumi Yohei , Nakamura Shinichiro , Joko Kouji , Iijima Hiroko , Kaibori Masaki , Hiasa Yoichi , Kudo Masatoshi ,   Real‐life Practice Experts for HCC (RELPEC) Study Group and HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan)
Published: June 2022

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.