Limited Impact of Anti-PD-1/PD-L1 Monotherapy for Hepatocellular Carcinoma

Kudo, Masatoshi

doi:10.1159/000512170

Cited by 26 publications

(21 citation statements)

References 27 publications

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“…Afterwards, the combination therapy revealed significantly better therapeutic outcomes and safety than sorafenib. In real-world clinical practice, the combination therapy can be used not only for the MTA-naïve cases but also the MTA-experienced cases as second- or third-line treatment [ 11 ]. Therefore, clarification is needed whether atezolizumab plus bevacizumab can be administered even for the MTA-experienced cases with safety.…”

Section: Introductionmentioning

confidence: 99%

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice

Iwamoto

Shimose

Noda

et al. 2021

Cancers

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Background: Atezolizumab plus bevacizumab was approved for patients with hepatocellular carcinoma (HCC). Although clinical trials have revealed its efficacy, the outcomes in the real-world clinical practice are unclear. We retrospectively evaluated the efficacy and safety of atezolizumab plus bevacizumab for HCC. Materials and Methods: This is a multicenter study conducted between November 2020 and March 2021. Among the 61 patients, 51 were assessed for progression-free survival (PFS), therapeutic response, and adverse events (AEs). Results: The median PFS was 5.4 months. The objective response rate (ORR) was 35.3%. The disease control rate (DCR) was 86.3%. The incidence rates of AEs at any grade and grade >3 were 98.0% and 29.4%, respectively. The most frequent AE at any grade and grade >3 was hepatic disorder. In patients with a previous history of molecular targeted agent (MTA) or the degree of albumin-bilirubin (ALBI) grade, there were no significant differences in the PFS, ORR, DCR, and incidence rates of AEs. Conclusion: The study demonstrated that atezolizumab plus bevacizumab was effective and safe for patients with HCC even in the real-world setting including patients with a previous MTA history or other than ALBI grade 1.

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Section: Introductionmentioning

confidence: 99%

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice

Iwamoto

Shimose

Noda

et al. 2021

Cancers

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“…This was precisely veri ed by the recent report by Chen et al, in which patients had increased PD-1 inhibitor treatment on the basis of TACE with improved oncological outcomes [14]. However, the role of PD-1 inhibitors for patients is also limited [34], and once a patient presents refractory to both PD-1 inhibitors and TACE, what treatment should be followed up, which is a question worth exploring and urgently resolving.…”

Section: Discussionmentioning

confidence: 97%

Efficacy of Stereotactic Body Radiation Therapy in Patients With Pd-1 Inhibitor–transarterial Chemoembolization Refractory Intermediate-stage Hepatocellular Carcinoma: a Retrospective Controlled Study

Xiang¹,

Wang²,

Zheng³

et al. 2021

Preprint

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Introduction: Transarterial chemoembolization (TACE) combined with PD-1 inhibitor is a novel and effective combination therapy. However, there is currently a gap in subsequent treatment when patients are diagnosed with PD-1 inhibitors-TACE refractoriness.Methods: This retrospective cohort study included enrolled patients with intermediate stage HCC who were diagnosed with PD-1 inhibitor-TACE refractoriness between January 2019 and December 2020 in the Eastern Hepatobiliary Surgery Hospital and the First Affiliated Hospital of Wenzhou Medical University. They were divided into two cohorts, (1) those who switched from TACE combined with PD-1 to stereotactic body radiation therapy (SBRT) combined with PD-1 and (2) those who continued TACE combined with PD-1. Progression free survival (PFS), overall survival (OS), and tumor response were assessed in both groups after refractory to PD-1 inhibitors combined with TACE.Results: Of the seventy-six patients included in this study, the median PFS was 19.6 months in the SBRT group (n=31) and 10.1 months in the TACE group (n=45, p<0.05). The SBRT group also had a significant higher OS than the TACE group (p<0.05). Objective response rate (ORR) and disease control rate (DCR) were also better in the SBRT group (ORR, 71.0% vs. 15.6%, OR=8.483, 95%CI 3.319-21.680, P < 0.001; DCR, 80.6% vs. 31.1%, OR=9.226, 95%CI 3.096-27.493, P < 0.001). Conclusions: SBRT combined with PD-1 inhibitor improves PFS and OS in patients refractory to PD-1 inhibitor combined with TACE. Therefore, SBRT is recommended in case of failure of treatment with PD-1 inhibitors combined with TACE.

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“…In 2020, Finn et al reported results from the phase Ib KEYNOTE 524 trial, that evaluated the (27). It is evident from the results of the above trials that immunotherapy in combination with other targeted therapies exhibit a superior antitumor activity compared to single-agent immunotherapy (28). Nonetheless, current evidence for combination treatment strategies arises from early-stage trials with small sample sizes.…”

Section: Review Articlementioning

confidence: 99%

Combination therapy for advanced hepatocellular carcinoma: do we see the light at the end of the tunnel?

Zhang

Merle

Wang

et al. 2021

Hepatobiliary Surg Nutr

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Importance: Combination therapies of anti-PD-1 and anti-angiogenesis regimens are emerging rapidly and exhibit more promising anti-tumor efficacy for advanced hepatocellular carcinoma (HCC), and consistently it is the hotspot in clinical studies.Objective: To elaborate several issues which are warranted further consideration as more regimens are being investigated in combination therapies.Evidence Review: We searched PubMed, MEDLINE, Cochrane Library and Google Scholar by 2021 February for publications on combination therapies for HCC.Findings: Several clinical issues are worth reconsidering, such as the evaluation on appropriate primary endpoints in phase III clinical trials as for different practical problems, the translation of surrogate endpoint objective response rate (ORR) benefits into overall survival (OS) benefits, and whether conversion surgery contributes to initial expectations of long-term survival or not. New concepts in novel immunotherapy and targeted therapy in combination with loco-regional therapies may improve overall survival for HCC.Conclusions and Relevance for Reviews: Comprehensive understanding of the mechanism of immunotherapy and targeted therapy contributes to better prognosis of advanced HCC and more explorative combination therapies are needed.

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Limited Impact of Anti-PD-1/PD-L1 Monotherapy for Hepatocellular Carcinoma

Cited by 26 publications

References 27 publications

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice

Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice

Efficacy of Stereotactic Body Radiation Therapy in Patients With Pd-1 Inhibitor–transarterial Chemoembolization Refractory Intermediate-stage Hepatocellular Carcinoma: a Retrospective Controlled Study

Combination therapy for advanced hepatocellular carcinoma: do we see the light at the end of the tunnel?

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