Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study

Persano, Mara; 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; Kawaguchi, Takumi; 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, Akira; Nakamura, Shinichiro; Kaibori, Masaki; Iijima, Hiroko; Hiasa, Yoichi; Cammarota, Antonella; Burgio, Valentina; Cascinu, Stefano; Casadei‐Gardini, Andrea

doi:10.1007/s00432-022-04512-1

Cited by 20 publications

(12 citation statements)

References 39 publications

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“…In the unmatched cohorts, LEN was associated with a better ORR compared to ATE/BEV with OR 1.34 (95% CI: 1.10-1.63, I 2 = 56%). However, in the analysis of matched cohorts from five studies ( n = 1174) [ 13 - 15 , 17 , 18 ], the ORR was comparable between the two groups (aOR = 1.15, 95% CI: 0.83-1.61, I 2 = 44%) ( Fig. 2A ).…”

Section: Resultsmentioning

confidence: 96%

“…Seven studies ( n = 4428) [ 12 - 18 ] and four studies ( n = 902) [ 14 , 15 , 17 , 18 ] reported the difference in DCR, respectively. There was no difference in DCR between LEN and ATE/BEV groups in both unmatched (OR = 0.91, 95% CI: 0.72-1.13, I 2 = 21%) and matched cohorts (aOR = 0.83, 95% CI: 0.49-1.38, I 2 = 53%) ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Seven studies reported the difference in PFS between the two groups [ 12 - 15 , 17 - 19 ]. Three studies reported a significantly longer PFS with ATE/LEN [ 14 , 15 , 19 ], while one reported a longer PFS with LEN [ 17 ] ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

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Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis

Giri,

Angadi,

Vaidya

et al. 2023

ceh

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Aim of the study Studies comparing atezolizumab plus bevacizumab (ATE/BEV) vs. lenvatinib (LEN) for advanced hepatocellular carcinoma (aHCC) have shown conflicting results. With this background, we aimed to collate the available evidence comparing ATE/BEV and LEN in aHCC. Material and methods A comprehensive search of three databases was conducted from inception to November 2022 for studies comparing ATE/BEV with LEN for managing aHCC. Results were presented with their 95% confidence intervals (95% CI) as the hazard ratio (HR) for time-to-event outcomes or odds ratios (OR) for dichotomous outcomes. Results A total of 8 studies were included. On analysis of matched cohorts, there was no difference in the objective response rate (ORR) (adjusted odds ratio [aOR] = 1.15, 95% CI: 0.83-1.61) or disease control rate (DCR) (aOR = 0.83, 95% CI: 0.49-1.38) between groups. Three studies reported a significantly longer progression-free survival (PFS) with ATE/LEN, while one reported a longer PFS with LEN. The adjusted hazard ratio (aHR) for PFS available from three studies was comparable (HR = 1.06, 95% CI: 0.75-1.50). Data were insufficient to carry out a formal analysis for overall survival (OS), but none of the studies reported any difference in OS. On comparison of overall adverse events (AE) and ≥ grade 3 AE, there was no difference in the overall analysis, but higher risk of AE with LEN on sensitivity analysis. Conclusions Based on the currently available literature, LEN was found to be non-inferior to ATE/BEV in terms of ORR, DCR, and PFS. However, LEN may be associated with a higher incidence of AEs. Further head-to-head trials are required to demonstrate the superiority of ATE/BEV over LEN.

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Section: Resultsmentioning

confidence: 96%

Section: Resultsmentioning

confidence: 99%

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Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis

Giri,

Angadi,

Vaidya

et al. 2023

ceh

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“…Notwithstanding these recommendations, a prevailing debate exists concerning which of the two is the most optimal for first-line treatment. Some investigations posit that AB is superior to lenvatinib in terms of OS ( 3 – 5 ), whereas alternative studies assert the contrary ( 6 , 7 ). Moreover, some reports indicated no significant difference in efficacy between the two regimens ( 8 – 10 ).…”

Section: Introductionmentioning

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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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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“…Interestingly, a recent propensity-matched (PSM) study that analyzed patients with non-viral HCC reported that lenvatinib resulted in better overall survival (OS) and progression-free survival (PFS) than AB treatment [ 4 ]. A recent large-scale, global, real-world study also reported that lenvatinib might be better than AB in advanced HCC in terms of objective response rate (ORR) [ 5 ]. Another real-world study using PSM and inverse probability of treatment weighting reported that two first-line treatments were comparable in terms of OS and PFS in unresectable HCC [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Higher Number of Tumor-Infiltrating PD-L1+ Cells Is Related to Better Response to Multikinase Inhibitors in Hepatocellular Carcinoma

Han

Kim

et al. 2023

Diagnostics

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Multikinase inhibitors (MKIs) such as sorafenib and lenvatinib are first-line treatments for unresectable hepatocellular carcinoma (HCC) and are known to have immunomodulatory effects. However, predictive biomarkers of MKI treatment in HCC patients need to be elucidated. In the present study, thirty consecutive HCC patients receiving lenvatinib (n = 22) and sorafenib (n = 8) who underwent core-needle biopsy before treatment were enrolled. The associations of CD3, CD68, and programmed cell death-ligand-1 (PD-L1) immunohistochemistry with patient outcomes, including overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), were evaluated. High and low subgroups were determined according to median CD3, CD68, and PD-L1 values. Median CD3 and CD68 counts were 51.0 and 46.0 per 20,000 µm2, respectively. The median combined positivity score (CPS) of PD-L1 was 2.0. Median OS and PFS were 17.6 and 4.4 months, respectively. ORRs of the total, lenvatinib, and sorafenib groups were 33.3% (10/30), 12.5% (1/8), and 40.9% (9/22), respectively. The high CD68+ group had significantly better PFS than the low CD68+ group. The high PD-L1 group had better PFS than the low subgroup. When we analyzed the lenvatinib subgroup, PFS was also significantly better in the high CD68+ and PD-L1 groups. These findings suggest that high numbers of PD-L1-expressing cells within tumor tissue prior to MKI treatment can serve as a biomarker to predict favorable PFS in HCC patients.

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Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study

Cited by 20 publications

References 39 publications

Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis

Atezolizumab plus bevacizumab versus lenvatinib as first-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis

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

Higher Number of Tumor-Infiltrating PD-L1+ Cells Is Related to Better Response to Multikinase Inhibitors in Hepatocellular Carcinoma

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