Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population

Casadei‐Gardini, Andrea; Rimini, Margherita; Tada, Toshifumi; Suda, Goki; Shimose, Shigeo; Kudo, Masatoshi; Cheon, Jaekyung; Finkelmeier, Fabian; Lim, Ho Yeong; Rimassa, Lorenza; Presa, José; Masi, Gianluca; Yoo, Changhoon; Tovoli, Francesco; Kumada, Takashi; Sakamoto, Naoya; Iwamoto, Hideki; Aoki, Tomoko; Chon, Hong Jae; Himmelsbach, Vera; Pressiani, Tiziana; Montes, Margarida; Vivaldi, Caterina; Soldà, Caterina; Piscaglia, Fabio; Hiraoka, Atsushi; Sho, Takuya; Nishizaki, Takashi; Nishida, Naoshi; Steup, Christoph; Iavarone, M.; Costanzo, G. Di; Marra, Fabio; Scartozzi, Mario; Tamburini, Emiliano; Cabibbo, Giuseppe; Foschi, Francesco Giuseppe; Silletta, Marianna; Hirooka, Masashi; Kariyama, Kazuya; Tani, Joji; Atsukawa, Masanori; Takaguchi, Koichi; Itobayashi, Ei; Fukunishi, Shinya; Tsuji, Kiichiro; Ishikawa, Toru; Tajiri, Kazuto; Ochi, Hironori; Yasuda, Satoshi; Toyoda, Hidenori; Ogawa, Chikara; Nishimura, Takashi; Hatanaka, Takeshi; Kakizaki, Satoru; Shimada, Noritomo; Kawata, Kazuhito; Tada, Fujimasa; Ohama, Hideko; Nouso, Kazuhiro; Morishita, Asahiro; Tsutsui, Akemi; Nagano, Takuya; Itokawa, Norio; Okubo, Tomomi; Arai, Taeang; Imai, Michitaka; Kosaka, Hisashi; Naganuma, Atsushi; Nakamura, Shinichiro; Kaibori, Masaki; Iijima, Hiroko; Hiasa, Yoichi; Burgio, Valentina; Persano, Mara; Corte, Angelo Della; Ratti, Francesca; Cobelli, Francesco De; Aldrighetti, Luca; Cascinu, Stefano; Cucchetti, Alessandro

doi:10.1016/j.ejca.2022.11.017

Cited by 70 publications

(43 citation statements)

References 26 publications

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“…Some studies showed that AB has superior OS ( 4 , 5 ) or PFS ( 3 – 5 ) compared to lenvatinib. Other reports showed that these two treatments have comparable OS and PFS ( 8 , 9 ). However, another study demonstrated that lenvatinib was associated with longer OS and PFS ( 6 ).…”

Section: Discussionmentioning

confidence: 91%

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Differential liver function at cessation of atezolizumab-bevacizumab versus lenvatinib in HCC: a multicenter, propensity-score matched comparative study

Han,

Sung,

Yoo

et al. 2024

Front. Oncol.

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BackgroundAtezolizumab+bevacizumab (AB) and lenvatinib have been proposed as first-line treatment options for patients with advanced hepatocellular carcinoma (HCC), but comparative efficacy and associated factors are controversial.Materials and methodsThis real-world multicenter study analysed patients with HCC who received AB (n=169) or lenvatinib (n=177).ResultsFirst, 1:1 propensity score matching (PSM) was performed, resulting in 141 patients in both the AB and lenvatinib groups. After PSM, overall survival (OS) was better in the AB group than in the lenvatinib group [hazard ratio (HR)=0.642, P=0.009], but progression-free survival (PFS) did not vary between the two groups (HR=0.817, P=0.132). Objective response rate (ORR) was also similar between AB and lenvatinib (34.8% vs. 30.8%, P=0.581). In a subgroup of patients with objective responses (OR, n=78), OS (HR=0.364, P=0.012) and PFS (HR=0.536, P=0.019) were better in the AB group (n=41) than in the lenvatinib group (n=37). Time-to-progression from time of OR was also better in the AB group (HR=0.465, P=0.012). Importantly, residual liver function was a significant factor related to OS in both treatments. Child-Pugh score following cessation of the respective treatments was better in the AB group (n=105) than in the lenvatinib group (n=126) (median 6 versus 7, P=0.008), and proportion of salvage treatment was also higher in the AB group (52.4% versus 38.9%, P=0.047). When we adjusted for residual liver function or salvage treatment, there was no difference in OS between the two treatments.ConclusionOur study suggests that residual liver function and subsequent salvage treatments are major determinants of clinical outcomes in patients treated with AB and lenvatinib; these factors should be considered in future comparative studies.

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Section: Discussionmentioning

confidence: 91%

“…Studies comparing these two regimens have conflicting results, although most studies used matched cohorts using PSM or inverse probability of treatment weighting ( 3 – 6 , 8 , 9 ). Some studies showed that AB has superior OS ( 4 , 5 ) or PFS ( 3 – 5 ) compared to lenvatinib.…”

Section: Discussionmentioning

confidence: 99%

Differential liver function at cessation of atezolizumab-bevacizumab versus lenvatinib in HCC: a multicenter, propensity-score matched comparative study

Han,

Sung,

Yoo

et al. 2024

Front. Oncol.

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“…Subsequent real-world studies observed a strikingly long survival in patients with MASLD-induced HCC treated with LEN. However, this needs to be confirmed in prospective studies[ 46 , 47 ].…”

Section: Treatmentmentioning

confidence: 99%

Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice

de Mattos,

Bombassaro,

Vogel

et al. 2024

World J Gastroenterol

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Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality. This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease. This makes the management of patients more challenging, since physicians must take into consideration two different conditions, the chronic liver disease and the tumor. The underlying liver disease has several implications in clinical practice, because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC, obstacles in surveillance, and differences in the efficacy of the treatment against HCC. A shift in the prevalence of liver diseases has been evident over the last few years, with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance. Therefore, in an era of personalized medicine, it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.

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“…62 Despite the enormous advancements made with this combination therapy, treatment with Lenvatinib versus treatment with Atezolizumab plus Bevacizumab has resulted in insignificant OS differences. 63 Due to PD-LI antibodies remaining bound to PD-1 receptors on cancer cells for more than 20 weeks, 64 researchers have begun thinking of sequential therapy as a possible solution, in which Lenvatinib would be given to the patient after failure with Atezolizumab plus Bevacizumab. 62,64,65 One of the reasons why Lenvatinib is thought to be an effective second-line treatment after Atezolizumab plus Bevacizumab is because Lenvatinib is more selective than Bevacizumab in terms of its antiangiogenesis properties, making it believed that sequential treatment could yield improvements in OS.…”

Section: Atezolizumab Plus Bevacizumabmentioning

confidence: 99%

The action and resistance mechanisms of Lenvatinib in liver cancer

Buttell,

Qiu

2023

Molecular Carcinogenesis

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Lenvatinib is a tyrosine kinase inhibitor that prevents the formation of new blood vessels namely by inhibiting tyrosine kinase enzymes as the name suggests. Specifically, Lenvatinib acts on vascular endothelial growth factor receptors 1−3 (VEGFR1−3), fibroblast growth factor receptors 1−4 (FGFR1−4), platelet‐derived growth factor receptor‐alpha (PDGFRα), tyrosine‐kinase receptor (KIT), and rearranged during transfection receptor (RET). Inhibition of these receptors works to inhibit tumor proliferation. It is through these inhibition mechanisms that Lenvatinib was tested to be noninferior to Sorafenib. However, resistance to Lenvatinib is common, making the positive effects of Lenvatinib on a patient's survival null after resistance is acquired. Therefore, it is crucial to understand mechanisms related to Lenvatinib resistance. This review aims to piece together various mechanisms involved in Lenvatinib resistance and summarizes the research done so far investigating it.

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Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population

Cited by 70 publications

References 26 publications

Differential liver function at cessation of atezolizumab-bevacizumab versus lenvatinib in HCC: a multicenter, propensity-score matched comparative study

Differential liver function at cessation of atezolizumab-bevacizumab versus lenvatinib in HCC: a multicenter, propensity-score matched comparative study

Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice

The action and resistance mechanisms of Lenvatinib in liver cancer

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