Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma

Abou‐Alfa, Ghassan K.; Lau, George; Kudo, Masatoshi; Chan, Stephen L.; Kelley, Robin Kate; Furuse, Junji; Sukeepaisarnjaroen, Wattana; Kang, Yoon‐Koo; Dao, Tu Van; Toni, Enrico N. De; Rimassa, Lorenza; Breder, Valeriy Vladimirovich; Vasilyev, Alexander; Heurgué, Alexandra; Tam, Vincent C.; Mody, Kabir; Thungappa, Satheesh Chiradoni; Ostapenko, Yuriy; Yau, Thomas; Azevedo, Sérgio Jobim; Varela, Marı́a; Cheng, Ann‐Lii; Qin, Shukui; Galle, Peter R.; Ali, Sajid; Marcovitz, Michelle; Makowsky, Mallory; He, Philip; Kurland, John F.; Negro, Alejandra; Sangro, Bruno

doi:10.1056/evidoa2100070

Cited by 654 publications

(683 citation statements)

References 23 publications

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“…Also, analysis by etiology showed the most favorable outcome was found in patients with non-viral etiology (Fig. 1) [14], a finding completely different from what had been believed.…”

Section: Treatment Effects Of Immune Checkpoint Inhibitors By Etiologycontrasting

confidence: 58%

“…The HR for OS over sorafenib was 0.78 (95% CI, 0.65-0.92). Subgroup analyses of HR for OS were 0.64 (95% CI, 0.48-0.86) in patients with HBV etiology, 1.06 (95% CI, 0.76-1.49) in those with HCV etiology, and 0.74 (95% CI, 0.57-0.95) in those with non-viral etiology [14] (Fig. 1, 2).…”

Section: Durvalumab Plus Tremelimumabmentioning

confidence: 93%

“…Comparison of progression-free survival by etiology (hazard ratio)[3][4][5][6][7][8]14]. HBV, hepatitis B virus; HCV, hepatitis C virus.…”

mentioning

confidence: 99%

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Selection of Systemic Treatment Regimen for Unresectable Hepatocellular Carcinoma: Does Etiology Matter?

Kudo¹

2022

Liver Cancer

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“…Also, analysis by etiology showed the most favorable outcome was found in patients with non-viral etiology (Fig. 1) [14], a finding completely different from what had been believed.…”

Section: Treatment Effects Of Immune Checkpoint Inhibitors By Etiologycontrasting

confidence: 58%

Section: Durvalumab Plus Tremelimumabmentioning

confidence: 93%

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Selection of Systemic Treatment Regimen for Unresectable Hepatocellular Carcinoma: Does Etiology Matter?

Kudo¹

2022

Liver Cancer

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“… 6 , 16 More recently, the combination of a single priming dose of tremelimumab, an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) mAb, plus durvalumab, an anti-PD-L1 mAb (STRIDE regimen) led to a significant overall survival (OS) advantage over sorafenib in the phase 3 HIMALAYA trial. 17 Of note, single-agent durvalumab was proven non-inferior to sorafenib in the same study. 17 Furthermore, cabozantinib plus atezolizumab significantly improved progression-free survival (PFS), one of the dual primary endpoints of the study, but not OS against sorafenib in the phase 3 COSMIC-312 trial.…”

Section: Introductionmentioning

confidence: 86%

Assessment and Monitoring of Response to Systemic Treatment in Advanced Hepatocellular Carcinoma: Current Insights

Cammarota¹,

Zanuso²,

Pressiani³

et al. 2022

JHC

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Advanced hepatocellular carcinoma (HCC) management has become more complex as novel therapies have been proven effective. After sorafenib, the approval of other multikinase inhibitors (MKIs) and immune checkpoints inhibitors (ICIs) has considerably increased the number of systemic therapies available. Therefore, careful assessment and monitoring of response to systemic treatment are essential to identify surrogate endpoints of overall survival (OS) in clinical trials and reliable tools to gauge treatment benefit in clinical practice. Progression-free survival (PFS) and objective response rate (ORR) are early informative parameters of efficacy that are not influenced by further lines of therapy. However, none of them has shown sufficient surrogacy to be recommended in place of OS in phase 3 trials. With such a wealth of therapeutic options, the prime intent of tumor assessments is no longer limited to identifying progressive disease to spare ineffective treatments to non-responders. Indeed, the early detection of responders could also help tailor treatment sequencing. Tumor assessment relies on the Response Evaluation Criteria for Solid Tumors (RECIST), which are easy to interpret – being based on dimensional principles – but could misread the activity of targeted agents. The HCC-specific modified RECIST (mRECIST), considering both the MKI-induced biological modifications and some of the cirrhosis-induced liver changes, better capture tumor response. Yet, mRECIST could not be considered a standard in advanced HCC. Further prognosticators including progression patterns, baseline and on-treatment liver function deterioration, and baseline alpha-fetoprotein (AFP) levels and AFP response have been extensively evaluated for MKIs. However, limited information is available for patients receiving ICIs and regarding their predictive role. Finally, there is increasing interest in incorporating novel imaging techniques which go beyond sizes and novel serum biomarkers in the advanced HCC framework. Hopefully, multiparametric models grouping dimensional and functional radiological parameters with biochemical markers will most precisely reflect treatment response.

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“…The approval of the atezolizumab-bevacizumab combination as the first-line treatment in HCC is the first notable example [19]. Recently, another combinational regimen of tremelimumab-durvalumab was shown to improve the median OS over that of sorafenib treatment in a phase III clinical trial [20]. The second approach is to develop methodologies to select patients who are more likely to derive benefits from the anti-PD-1/PDL-1 treatment.…”

Section: Introductionmentioning

confidence: 99%

Could We Predict the Response of Immune Checkpoint Inhibitor Treatment in Hepatocellular Carcinoma?

Lee

Chan

Chon

2022

Cancers

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The use of anti-programmed cell-death protein (ligand)-1 (PD-[L]1) is an important strategy for treating hepatocellular carcinoma (HCC). However, the treatment only benefits 10–20% of patients when used as a monotherapy. Therefore, the selection of patients for anti-PD-1/PD-L1 treatment is crucial for both patients and clinicians. This review aimed to explore the existing literature on tissue or circulating markers for the identification of responders or non-responders to anti-PD-1/PD-L1 in HCC. For the clinically available markers, both etiological factors (viral versus non-viral) and disease extent (intra-hepatic vs. extrahepatic) impact the responses to anti-PD-1/PD-L1, warranting further studies. Preliminary data suggested that inflammatory indices (e.g., neutrophil-lymphocyte ratio) may be associated with clinical outcomes of HCC during the anti-PD-1/PD-L1 treatment. Finally, although PD-L1 expression in tumor tissues is a predictive marker for multiple cancer types, its clinical application is less clear in HCC due to the lack of a clear-cut association with responders to anti-PD-1/PD-L1 treatment. Although all translational markers are not routinely measured in HCC, recent data suggest their potential roles in selecting patients for anti-PD-1/PD-L1 treatment. Such markers, including the immune classification of HCC, selected signaling pathways, tumor-infiltrating lymphocytes, and auto-antibodies, were discussed in this review.

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Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma

Cited by 654 publications

References 23 publications

Selection of Systemic Treatment Regimen for Unresectable Hepatocellular Carcinoma: Does Etiology Matter?

Selection of Systemic Treatment Regimen for Unresectable Hepatocellular Carcinoma: Does Etiology Matter?

Assessment and Monitoring of Response to Systemic Treatment in Advanced Hepatocellular Carcinoma: Current Insights

Could We Predict the Response of Immune Checkpoint Inhibitor Treatment in Hepatocellular Carcinoma?

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