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mRECIST objective response and early tumor shrinkage predict survival in sorafenib-treated HCC

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Key clinical point: Modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined objective response (OR) and early tumor shrinkage (ETS) may serve as independent prognostic factors for overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) on sorafenib monotherapy.

Main finding: OR assessed by mRECIST (adjusted hazard ratio [aHR], 0.32; P < .001) and ETS (aHR, 0.44; P < .001) were independent prognostic factors for OS. A longer median OS was shown by responders vs nonresponders (30.3 months vs 11.4 months; P < .001) and by patients with ETS ≥20% vs those with ETS <20% (22.1 months vs 11.4 months; P < .001).

Study details: This was a post hoc analysis of data from the phase 2 SORAMIC trial and included 115 patients with advanced HCC receiving sorafenib monotherapy.

Disclosures: The study was sponsored by Sirtex Medical and Bayer Healthcare. Some of the authors declared receiving personal fees and research grants from various sources including Bayer and Sirtex.

Source: Öcal O et al. Cancer Imaging. 2022 Jan 4. doi: 10.1186/s40644-021-00439-x.

 

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Key clinical point: Modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined objective response (OR) and early tumor shrinkage (ETS) may serve as independent prognostic factors for overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) on sorafenib monotherapy.

Main finding: OR assessed by mRECIST (adjusted hazard ratio [aHR], 0.32; P < .001) and ETS (aHR, 0.44; P < .001) were independent prognostic factors for OS. A longer median OS was shown by responders vs nonresponders (30.3 months vs 11.4 months; P < .001) and by patients with ETS ≥20% vs those with ETS <20% (22.1 months vs 11.4 months; P < .001).

Study details: This was a post hoc analysis of data from the phase 2 SORAMIC trial and included 115 patients with advanced HCC receiving sorafenib monotherapy.

Disclosures: The study was sponsored by Sirtex Medical and Bayer Healthcare. Some of the authors declared receiving personal fees and research grants from various sources including Bayer and Sirtex.

Source: Öcal O et al. Cancer Imaging. 2022 Jan 4. doi: 10.1186/s40644-021-00439-x.

 

Key clinical point: Modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined objective response (OR) and early tumor shrinkage (ETS) may serve as independent prognostic factors for overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) on sorafenib monotherapy.

Main finding: OR assessed by mRECIST (adjusted hazard ratio [aHR], 0.32; P < .001) and ETS (aHR, 0.44; P < .001) were independent prognostic factors for OS. A longer median OS was shown by responders vs nonresponders (30.3 months vs 11.4 months; P < .001) and by patients with ETS ≥20% vs those with ETS <20% (22.1 months vs 11.4 months; P < .001).

Study details: This was a post hoc analysis of data from the phase 2 SORAMIC trial and included 115 patients with advanced HCC receiving sorafenib monotherapy.

Disclosures: The study was sponsored by Sirtex Medical and Bayer Healthcare. Some of the authors declared receiving personal fees and research grants from various sources including Bayer and Sirtex.

Source: Öcal O et al. Cancer Imaging. 2022 Jan 4. doi: 10.1186/s40644-021-00439-x.

 

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HCC: AFP <500 ng/mL at liver transplant even in patients with moderately elevated AFP may mend posttransplant outcomes

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Key clinical point: Lowering the current United Network for Organ Sharing-recommended alpha-fetoprotein (AFP) level threshold for exclusion from liver transplant (LT) to ≥500 ng/mL for all patients with hepatocellular carcinoma (HCC) instead of only for those with AFP levels >1000 ng/mL could improve post-LT outcomes.

Main finding: After multivariable adjustment, an AFP level ≥500 ng/mL at LT was associated with an elevated risk of post-LT mortality (adjusted hazard ratio [aHR], 1.5; P = .02) and HCC recurrence (aHR, 1.88; P = .02) compared with an AFP level <100 ng/mL.

Study details: This was a retrospective cohort study involving 1,766 adult patients with HCC who had undergone LT and had listing AFP levels between 100 ng/mL and 999 ng/mL at initial model for end-stage liver disease exception.

Disclosures: The study was funded by the UCSF Clinical and Translational Science Institute Research Funding Award and UCSF Liver Center. Some of the authors reported being on the advisory board of or receiving research grants from various organizations.

Source: Goldman ML et al. Liver Transpl. 2021 Dec 20. doi: 10.1002/lt.26392.

 

 

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Key clinical point: Lowering the current United Network for Organ Sharing-recommended alpha-fetoprotein (AFP) level threshold for exclusion from liver transplant (LT) to ≥500 ng/mL for all patients with hepatocellular carcinoma (HCC) instead of only for those with AFP levels >1000 ng/mL could improve post-LT outcomes.

Main finding: After multivariable adjustment, an AFP level ≥500 ng/mL at LT was associated with an elevated risk of post-LT mortality (adjusted hazard ratio [aHR], 1.5; P = .02) and HCC recurrence (aHR, 1.88; P = .02) compared with an AFP level <100 ng/mL.

Study details: This was a retrospective cohort study involving 1,766 adult patients with HCC who had undergone LT and had listing AFP levels between 100 ng/mL and 999 ng/mL at initial model for end-stage liver disease exception.

Disclosures: The study was funded by the UCSF Clinical and Translational Science Institute Research Funding Award and UCSF Liver Center. Some of the authors reported being on the advisory board of or receiving research grants from various organizations.

Source: Goldman ML et al. Liver Transpl. 2021 Dec 20. doi: 10.1002/lt.26392.

 

 

Key clinical point: Lowering the current United Network for Organ Sharing-recommended alpha-fetoprotein (AFP) level threshold for exclusion from liver transplant (LT) to ≥500 ng/mL for all patients with hepatocellular carcinoma (HCC) instead of only for those with AFP levels >1000 ng/mL could improve post-LT outcomes.

Main finding: After multivariable adjustment, an AFP level ≥500 ng/mL at LT was associated with an elevated risk of post-LT mortality (adjusted hazard ratio [aHR], 1.5; P = .02) and HCC recurrence (aHR, 1.88; P = .02) compared with an AFP level <100 ng/mL.

Study details: This was a retrospective cohort study involving 1,766 adult patients with HCC who had undergone LT and had listing AFP levels between 100 ng/mL and 999 ng/mL at initial model for end-stage liver disease exception.

Disclosures: The study was funded by the UCSF Clinical and Translational Science Institute Research Funding Award and UCSF Liver Center. Some of the authors reported being on the advisory board of or receiving research grants from various organizations.

Source: Goldman ML et al. Liver Transpl. 2021 Dec 20. doi: 10.1002/lt.26392.

 

 

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Persistent and incident body fatness is strongly associated with HCC development

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Key clinical point: Individuals with persistent or incident body fatness show an increased risk of developing hepatocellular carcinoma (HCC).

Main finding: Compared with their persistent no-fatness counterparts, both general fatness (persistent: adjusted hazard ratio [aHR], 1.28; 95% CI, 1.23-1.34; incident: aHR, 1.10; 95% CI, 1.01-1.20) and central fatness (persistent: aHR, 1.33; 95% CI, 1.26-1.40; incident: aHR, 1.19; 95% CI, 1.11-1.27) were associated with an increased risk of HCC.

Study details: The data come from a nationwide population-based cohort study including 6,789,472 individuals aged 20 years or older who were not previously diagnosed with HCC and underwent health examinations twice with a gap of 2 years.

Disclosures: The study was sponsored by the Research Supporting Program of The Korean Association for the Study of the Liver and the Korean Liver Foundation. The authors declared no conflict of interests.

Source: Kim MN et al. Int J Cancer. 2021 Dec 26. doi: 10.1002/ijc.33920.

 

 

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Key clinical point: Individuals with persistent or incident body fatness show an increased risk of developing hepatocellular carcinoma (HCC).

Main finding: Compared with their persistent no-fatness counterparts, both general fatness (persistent: adjusted hazard ratio [aHR], 1.28; 95% CI, 1.23-1.34; incident: aHR, 1.10; 95% CI, 1.01-1.20) and central fatness (persistent: aHR, 1.33; 95% CI, 1.26-1.40; incident: aHR, 1.19; 95% CI, 1.11-1.27) were associated with an increased risk of HCC.

Study details: The data come from a nationwide population-based cohort study including 6,789,472 individuals aged 20 years or older who were not previously diagnosed with HCC and underwent health examinations twice with a gap of 2 years.

Disclosures: The study was sponsored by the Research Supporting Program of The Korean Association for the Study of the Liver and the Korean Liver Foundation. The authors declared no conflict of interests.

Source: Kim MN et al. Int J Cancer. 2021 Dec 26. doi: 10.1002/ijc.33920.

 

 

Key clinical point: Individuals with persistent or incident body fatness show an increased risk of developing hepatocellular carcinoma (HCC).

Main finding: Compared with their persistent no-fatness counterparts, both general fatness (persistent: adjusted hazard ratio [aHR], 1.28; 95% CI, 1.23-1.34; incident: aHR, 1.10; 95% CI, 1.01-1.20) and central fatness (persistent: aHR, 1.33; 95% CI, 1.26-1.40; incident: aHR, 1.19; 95% CI, 1.11-1.27) were associated with an increased risk of HCC.

Study details: The data come from a nationwide population-based cohort study including 6,789,472 individuals aged 20 years or older who were not previously diagnosed with HCC and underwent health examinations twice with a gap of 2 years.

Disclosures: The study was sponsored by the Research Supporting Program of The Korean Association for the Study of the Liver and the Korean Liver Foundation. The authors declared no conflict of interests.

Source: Kim MN et al. Int J Cancer. 2021 Dec 26. doi: 10.1002/ijc.33920.

 

 

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Surgery vs radiofrequency ablation: Achieving better recurrence-free survival in small HCC

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Key clinical point: Patients with small hepatocellular carcinoma (HCC) show a comparable improvement in recurrence-free survival (RFS) after undergoing surgery or radiofrequency ablation (RFA).

Main finding: The median RFS of patients who had undergone surgery was not significantly different from that of patients receiving RFA (3.46 years vs 3.04 years; hazard ratio, 0.92; P = .58).

Study details: Findings are from the phase 3 SURF-trial including 301 patients aged between 20 and 80 years with the largest HCC diameter ≤3 cm and ≤3 HCC nodules who were randomly assigned (1:1) to undergo either surgery (n=150) or RFA (n=151).

Disclosures: The study was sponsored by the Japanese Foundation for Multidisciplinary Treatment of Cancer and the Health and Labor Sciences Research Grant for Clinical Cancer Research. Some of the authors declared receiving lecture fees or research funds from or serving as an advisor for various companies. A few authors reported being on the editorial team/board of Liver Cancer.

Source: Takayama T et al. Liver Cancer. 2021 Dec 29. doi: 10.1159/000521665.

 

 

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Key clinical point: Patients with small hepatocellular carcinoma (HCC) show a comparable improvement in recurrence-free survival (RFS) after undergoing surgery or radiofrequency ablation (RFA).

Main finding: The median RFS of patients who had undergone surgery was not significantly different from that of patients receiving RFA (3.46 years vs 3.04 years; hazard ratio, 0.92; P = .58).

Study details: Findings are from the phase 3 SURF-trial including 301 patients aged between 20 and 80 years with the largest HCC diameter ≤3 cm and ≤3 HCC nodules who were randomly assigned (1:1) to undergo either surgery (n=150) or RFA (n=151).

Disclosures: The study was sponsored by the Japanese Foundation for Multidisciplinary Treatment of Cancer and the Health and Labor Sciences Research Grant for Clinical Cancer Research. Some of the authors declared receiving lecture fees or research funds from or serving as an advisor for various companies. A few authors reported being on the editorial team/board of Liver Cancer.

Source: Takayama T et al. Liver Cancer. 2021 Dec 29. doi: 10.1159/000521665.

 

 

Key clinical point: Patients with small hepatocellular carcinoma (HCC) show a comparable improvement in recurrence-free survival (RFS) after undergoing surgery or radiofrequency ablation (RFA).

Main finding: The median RFS of patients who had undergone surgery was not significantly different from that of patients receiving RFA (3.46 years vs 3.04 years; hazard ratio, 0.92; P = .58).

Study details: Findings are from the phase 3 SURF-trial including 301 patients aged between 20 and 80 years with the largest HCC diameter ≤3 cm and ≤3 HCC nodules who were randomly assigned (1:1) to undergo either surgery (n=150) or RFA (n=151).

Disclosures: The study was sponsored by the Japanese Foundation for Multidisciplinary Treatment of Cancer and the Health and Labor Sciences Research Grant for Clinical Cancer Research. Some of the authors declared receiving lecture fees or research funds from or serving as an advisor for various companies. A few authors reported being on the editorial team/board of Liver Cancer.

Source: Takayama T et al. Liver Cancer. 2021 Dec 29. doi: 10.1159/000521665.

 

 

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ABO blood group system may dictate the outcome of liver transplantation in HCC

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Key clinical point: The oncological outcome in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT) is strongly affected by the ABO blood group system.

Main finding: Blood group A showed an independent association with increased tumor recurrence risk (adjusted hazard ratio [aHR], 1.574; P = .034) with group A vs non-A recipients having higher 5-year tumor recurrence rates (20.1% vs 13.2%; aHR, 1.66; P = .011) and lower 5-year recurrence-free survival rates (66.8% vs 71.3%; aHR, 1.38; P = .045).

Study details: The data are derived from a multicentric retrospective observational study including 925 adult patients with HCC who underwent LT, of whom 406, 94, 380, and 45 had blood group A, B, O, and AB, respectively.

Disclosures: The authors reported no funding source or conflict of interests.

Source: Kayvan M et al. Transplantation. 2021 Dec 27. doi: 10.1097/TP.0000000000004004.

 

 

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Key clinical point: The oncological outcome in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT) is strongly affected by the ABO blood group system.

Main finding: Blood group A showed an independent association with increased tumor recurrence risk (adjusted hazard ratio [aHR], 1.574; P = .034) with group A vs non-A recipients having higher 5-year tumor recurrence rates (20.1% vs 13.2%; aHR, 1.66; P = .011) and lower 5-year recurrence-free survival rates (66.8% vs 71.3%; aHR, 1.38; P = .045).

Study details: The data are derived from a multicentric retrospective observational study including 925 adult patients with HCC who underwent LT, of whom 406, 94, 380, and 45 had blood group A, B, O, and AB, respectively.

Disclosures: The authors reported no funding source or conflict of interests.

Source: Kayvan M et al. Transplantation. 2021 Dec 27. doi: 10.1097/TP.0000000000004004.

 

 

Key clinical point: The oncological outcome in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT) is strongly affected by the ABO blood group system.

Main finding: Blood group A showed an independent association with increased tumor recurrence risk (adjusted hazard ratio [aHR], 1.574; P = .034) with group A vs non-A recipients having higher 5-year tumor recurrence rates (20.1% vs 13.2%; aHR, 1.66; P = .011) and lower 5-year recurrence-free survival rates (66.8% vs 71.3%; aHR, 1.38; P = .045).

Study details: The data are derived from a multicentric retrospective observational study including 925 adult patients with HCC who underwent LT, of whom 406, 94, 380, and 45 had blood group A, B, O, and AB, respectively.

Disclosures: The authors reported no funding source or conflict of interests.

Source: Kayvan M et al. Transplantation. 2021 Dec 27. doi: 10.1097/TP.0000000000004004.

 

 

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Clinical Edge Journal Scan Commentary: HCC January 2022

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Dr. Damjanov scans the journals, so you don’t have to!

Nevena Damjanov, MD
Several novel options for the treatment of unresectable hepatocellular carcinoma (uHCC) have been evaluated over the past few years. This month, we will review recently published articles that address systemic therapies for uHCC.

For many years, sorafenib was the only FDA-approved systemic treatment for patients with uHCC. Initial case reports of remarkable responses of tumors to immunotherapy, and results of the Phase I/II CheckMate-040 clinical trial, led to the September 2017 FDA approval of nivolumab for the treatment of patients with uHCC after progression on sorafenib. Thereafter, several randomized clinical trials comparing sorafenib to immunotherapy and immunotherapy combinations were initiated, including the comparison of nivolumab to sorafenib. In June 2019 it was announced that this trial did not reach its prespecified endpoint, and the FDA approval for the uHCC indication was voluntarily withdrawn. In December 2021, Yau et al published the final results of the CheckMate-459 randomized trial that included 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372) in the first line setting.  The primary endpoint was overall survival (OS) assessed in the intention-to-treat population. The median OS was 16.4 months (95% CI 13.9–18.4) with nivolumab and 14.7 months (11.9–17.2) with sorafenib (hazard ratio 0.85 [95% CI 0.72–1.02]; P = 0.075; minimum follow-up 22.8 months). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. The authors concluded that though first-line nivolumab treatment did not significantly improve OS compared with sorafenib, single-agent nivolumab might be considered a treatment option for patients in whom tyrosine kinase inhibitors or antiangiogenic drugs are not safe.

Cheng et al reported an update on the outcomes of the IMbrave150 study, 12 months after the primary analysis. This study established atezolizumab and bevacizumab as the current standard of care for the initial systemic treatment of patients with uHCC. The median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab/bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR], 0.66; 95% CI 0.52-0.85; descriptive P < 0.001). The overall response rate (ORR) was 30% with atezolizumab/bevacizumab, while treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 receiving atezolizumab/bevacizumab and 72 (46%) of 156 receiving sorafenib. Treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients. Therefore, atezolizumab/bevacizumab remains the first-line standard of care for patients with uHCC.

Finally, Jácome et al undertook a combined analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), with 1,657 patients with uHCC and who were treated with either immunotherapy (n=985) or sorafenib (in the first-line setting) or placebo (in the sorafenib-refractory setting) (n=672). The conclusion of the meta-analysis was that checkpoint inhibitors were associated with superior OS (HR, 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and ORR (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04) than the comparators, confirming that immunotherapy remains an integral part of the treatment of patients with uHCC.

 

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Nevena Damjanov, MD, Professor, Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania; Chief, Department of Hematology-Oncology,  Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania

Nevena Damjanov, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: QED; Eisai

Received research grant from: Basilea; Bristol-Myers Squibb; Merck

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Nevena Damjanov, MD, Professor, Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania; Chief, Department of Hematology-Oncology,  Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania

Nevena Damjanov, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: QED; Eisai

Received research grant from: Basilea; Bristol-Myers Squibb; Merck

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Nevena Damjanov, MD, Professor, Department of Medicine, Division of Hematology-Oncology, University of Pennsylvania; Chief, Department of Hematology-Oncology,  Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania

Nevena Damjanov, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: QED; Eisai

Received research grant from: Basilea; Bristol-Myers Squibb; Merck

Dr. Damjanov scans the journals, so you don’t have to!
Dr. Damjanov scans the journals, so you don’t have to!

Nevena Damjanov, MD
Several novel options for the treatment of unresectable hepatocellular carcinoma (uHCC) have been evaluated over the past few years. This month, we will review recently published articles that address systemic therapies for uHCC.

For many years, sorafenib was the only FDA-approved systemic treatment for patients with uHCC. Initial case reports of remarkable responses of tumors to immunotherapy, and results of the Phase I/II CheckMate-040 clinical trial, led to the September 2017 FDA approval of nivolumab for the treatment of patients with uHCC after progression on sorafenib. Thereafter, several randomized clinical trials comparing sorafenib to immunotherapy and immunotherapy combinations were initiated, including the comparison of nivolumab to sorafenib. In June 2019 it was announced that this trial did not reach its prespecified endpoint, and the FDA approval for the uHCC indication was voluntarily withdrawn. In December 2021, Yau et al published the final results of the CheckMate-459 randomized trial that included 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372) in the first line setting.  The primary endpoint was overall survival (OS) assessed in the intention-to-treat population. The median OS was 16.4 months (95% CI 13.9–18.4) with nivolumab and 14.7 months (11.9–17.2) with sorafenib (hazard ratio 0.85 [95% CI 0.72–1.02]; P = 0.075; minimum follow-up 22.8 months). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. The authors concluded that though first-line nivolumab treatment did not significantly improve OS compared with sorafenib, single-agent nivolumab might be considered a treatment option for patients in whom tyrosine kinase inhibitors or antiangiogenic drugs are not safe.

Cheng et al reported an update on the outcomes of the IMbrave150 study, 12 months after the primary analysis. This study established atezolizumab and bevacizumab as the current standard of care for the initial systemic treatment of patients with uHCC. The median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab/bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR], 0.66; 95% CI 0.52-0.85; descriptive P < 0.001). The overall response rate (ORR) was 30% with atezolizumab/bevacizumab, while treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 receiving atezolizumab/bevacizumab and 72 (46%) of 156 receiving sorafenib. Treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients. Therefore, atezolizumab/bevacizumab remains the first-line standard of care for patients with uHCC.

Finally, Jácome et al undertook a combined analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), with 1,657 patients with uHCC and who were treated with either immunotherapy (n=985) or sorafenib (in the first-line setting) or placebo (in the sorafenib-refractory setting) (n=672). The conclusion of the meta-analysis was that checkpoint inhibitors were associated with superior OS (HR, 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and ORR (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04) than the comparators, confirming that immunotherapy remains an integral part of the treatment of patients with uHCC.

 

Nevena Damjanov, MD
Several novel options for the treatment of unresectable hepatocellular carcinoma (uHCC) have been evaluated over the past few years. This month, we will review recently published articles that address systemic therapies for uHCC.

For many years, sorafenib was the only FDA-approved systemic treatment for patients with uHCC. Initial case reports of remarkable responses of tumors to immunotherapy, and results of the Phase I/II CheckMate-040 clinical trial, led to the September 2017 FDA approval of nivolumab for the treatment of patients with uHCC after progression on sorafenib. Thereafter, several randomized clinical trials comparing sorafenib to immunotherapy and immunotherapy combinations were initiated, including the comparison of nivolumab to sorafenib. In June 2019 it was announced that this trial did not reach its prespecified endpoint, and the FDA approval for the uHCC indication was voluntarily withdrawn. In December 2021, Yau et al published the final results of the CheckMate-459 randomized trial that included 743 adult patients with advanced HCC randomly assigned to receive either nivolumab (n=371) or sorafenib (n=372) in the first line setting.  The primary endpoint was overall survival (OS) assessed in the intention-to-treat population. The median OS was 16.4 months (95% CI 13.9–18.4) with nivolumab and 14.7 months (11.9–17.2) with sorafenib (hazard ratio 0.85 [95% CI 0.72–1.02]; P = 0.075; minimum follow-up 22.8 months). Serious treatment-related adverse events were reported in 43 (12%) patients receiving nivolumab and 39 (11%) patients receiving sorafenib. The authors concluded that though first-line nivolumab treatment did not significantly improve OS compared with sorafenib, single-agent nivolumab might be considered a treatment option for patients in whom tyrosine kinase inhibitors or antiangiogenic drugs are not safe.

Cheng et al reported an update on the outcomes of the IMbrave150 study, 12 months after the primary analysis. This study established atezolizumab and bevacizumab as the current standard of care for the initial systemic treatment of patients with uHCC. The median OS was 19.2 months (95% CI 17.0-23.7) with atezolizumab/bevacizumab and 13.4 months (95% CI 11.4-16.9) with sorafenib (hazard ratio [HR], 0.66; 95% CI 0.52-0.85; descriptive P < 0.001). The overall response rate (ORR) was 30% with atezolizumab/bevacizumab, while treatment-related grade 3/4 adverse events occurred in 143 (43%) of 329 receiving atezolizumab/bevacizumab and 72 (46%) of 156 receiving sorafenib. Treatment-related grade 5 events occurred in 6 (2%) and 1 (<1%) patients. Therefore, atezolizumab/bevacizumab remains the first-line standard of care for patients with uHCC.

Finally, Jácome et al undertook a combined analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), with 1,657 patients with uHCC and who were treated with either immunotherapy (n=985) or sorafenib (in the first-line setting) or placebo (in the sorafenib-refractory setting) (n=672). The conclusion of the meta-analysis was that checkpoint inhibitors were associated with superior OS (HR, 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and ORR (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04) than the comparators, confirming that immunotherapy remains an integral part of the treatment of patients with uHCC.

 

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mTORi-based immunosuppression prolongs post-liver transplant survival in HCC

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Key clinical point: Among patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT), a treatment regimen consisting of sirolimus- or everolimus-based immunosuppression prolonged survival compared with mammalian target of rapamycin inhibitor (mTORi)-free immunosuppression.

Major finding: Improvement in overall survival was observed with mTORi-based vs mTORi-free immunosuppression in both randomized controlled trials (RCTs; 1 year: relative risk [RR], 1.04; 95% CI, 1.00-1.08; 5 years: RR, 1.13; 95% CI, 1.02-1.26) and cohort studies (1 year: RR, 1.13; 95% CI, 1.06-1.20; 5 years: RR, 1.17; 95% CI, 1.10-1.24).

Study details: Findings are from a meta-analysis of 17 studies (RCTs, 3; cohort studies, 14) including adult patients undergoing LT for HCC who received mTORi-based or mTORi-free immunosuppression.

Disclosures: The study was supported by the National Natural Science Foundation of China. No conflict of interests was reported.

Source: Yan X et al. Liver Transpl. 2021 Dec 16. doi: 10.1002/lt.26387.

 

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Key clinical point: Among patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT), a treatment regimen consisting of sirolimus- or everolimus-based immunosuppression prolonged survival compared with mammalian target of rapamycin inhibitor (mTORi)-free immunosuppression.

Major finding: Improvement in overall survival was observed with mTORi-based vs mTORi-free immunosuppression in both randomized controlled trials (RCTs; 1 year: relative risk [RR], 1.04; 95% CI, 1.00-1.08; 5 years: RR, 1.13; 95% CI, 1.02-1.26) and cohort studies (1 year: RR, 1.13; 95% CI, 1.06-1.20; 5 years: RR, 1.17; 95% CI, 1.10-1.24).

Study details: Findings are from a meta-analysis of 17 studies (RCTs, 3; cohort studies, 14) including adult patients undergoing LT for HCC who received mTORi-based or mTORi-free immunosuppression.

Disclosures: The study was supported by the National Natural Science Foundation of China. No conflict of interests was reported.

Source: Yan X et al. Liver Transpl. 2021 Dec 16. doi: 10.1002/lt.26387.

 

Key clinical point: Among patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT), a treatment regimen consisting of sirolimus- or everolimus-based immunosuppression prolonged survival compared with mammalian target of rapamycin inhibitor (mTORi)-free immunosuppression.

Major finding: Improvement in overall survival was observed with mTORi-based vs mTORi-free immunosuppression in both randomized controlled trials (RCTs; 1 year: relative risk [RR], 1.04; 95% CI, 1.00-1.08; 5 years: RR, 1.13; 95% CI, 1.02-1.26) and cohort studies (1 year: RR, 1.13; 95% CI, 1.06-1.20; 5 years: RR, 1.17; 95% CI, 1.10-1.24).

Study details: Findings are from a meta-analysis of 17 studies (RCTs, 3; cohort studies, 14) including adult patients undergoing LT for HCC who received mTORi-based or mTORi-free immunosuppression.

Disclosures: The study was supported by the National Natural Science Foundation of China. No conflict of interests was reported.

Source: Yan X et al. Liver Transpl. 2021 Dec 16. doi: 10.1002/lt.26387.

 

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HCC: Percutaneous radiofrequency ablation outcomes not associated with NAFLD or MS

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Key clinical point: The presence of nonalcoholic fatty liver disease (NAFLD) or metabolic syndrome (MS) did not affect the long-term oncological outcomes in patients with hepatocellular carcinoma (HCC) treated with multibipolar percutaneous radiofrequency ablation (RFA).

Major finding: Neither NAFLD-HCC nor MS was associated with overall tumor recurrence (hazard ratio [HR], 1.12; P = .536 and HR, 0.99; P = .965, respectively) or overall survival (HR, 1.19; P = .45 and HR, 0.99; P = .980, respectively).

Study details: This multicenter retrospective study included 520 adult patients with HCC who underwent first-line multibipolar percutaneous RFA treatment.

Disclosures: The study did not receive any specific funding. T Dao, N Ganne-Carrié, and JC Nault reported receiving grants, speaker’s fees, personal fees, or invitations for medical meetings from various pharmaceutical companies.

Source: Nguyen N et al. Liver Int. 2021 Dec 11. doi: 10.1111/liv.15129.

 

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Key clinical point: The presence of nonalcoholic fatty liver disease (NAFLD) or metabolic syndrome (MS) did not affect the long-term oncological outcomes in patients with hepatocellular carcinoma (HCC) treated with multibipolar percutaneous radiofrequency ablation (RFA).

Major finding: Neither NAFLD-HCC nor MS was associated with overall tumor recurrence (hazard ratio [HR], 1.12; P = .536 and HR, 0.99; P = .965, respectively) or overall survival (HR, 1.19; P = .45 and HR, 0.99; P = .980, respectively).

Study details: This multicenter retrospective study included 520 adult patients with HCC who underwent first-line multibipolar percutaneous RFA treatment.

Disclosures: The study did not receive any specific funding. T Dao, N Ganne-Carrié, and JC Nault reported receiving grants, speaker’s fees, personal fees, or invitations for medical meetings from various pharmaceutical companies.

Source: Nguyen N et al. Liver Int. 2021 Dec 11. doi: 10.1111/liv.15129.

 

Key clinical point: The presence of nonalcoholic fatty liver disease (NAFLD) or metabolic syndrome (MS) did not affect the long-term oncological outcomes in patients with hepatocellular carcinoma (HCC) treated with multibipolar percutaneous radiofrequency ablation (RFA).

Major finding: Neither NAFLD-HCC nor MS was associated with overall tumor recurrence (hazard ratio [HR], 1.12; P = .536 and HR, 0.99; P = .965, respectively) or overall survival (HR, 1.19; P = .45 and HR, 0.99; P = .980, respectively).

Study details: This multicenter retrospective study included 520 adult patients with HCC who underwent first-line multibipolar percutaneous RFA treatment.

Disclosures: The study did not receive any specific funding. T Dao, N Ganne-Carrié, and JC Nault reported receiving grants, speaker’s fees, personal fees, or invitations for medical meetings from various pharmaceutical companies.

Source: Nguyen N et al. Liver Int. 2021 Dec 11. doi: 10.1111/liv.15129.

 

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Meta-analysis favors ICIs over standard care in unresectable HCC

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Key clinical point: Treatment with immune checkpoint inhibitors (ICIs) was associated with prolonged survival and better safety compared with standard care in patients with unresectable hepatocellular carcinoma (HCC).

Major finding: ICIs vs standard care were associated with superior overall survival (hazard ratio [HR], 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and overall response rate (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04).

Study details: Findings are from a meta-analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), including 1,657 patients with unresectable HCC treated with either ICIs (n=985) or standard care (n=672).

Disclosures: No source of funding was identified. The lead author and JPS Vasconcelos received grants and/or personal fees from various pharmaceutical companies.

Source: Jácome AA et al. JAMA Netw Open. 2021 Dec 6. doi: 10.1001/jamanetworkopen.2021.36128.

 

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Key clinical point: Treatment with immune checkpoint inhibitors (ICIs) was associated with prolonged survival and better safety compared with standard care in patients with unresectable hepatocellular carcinoma (HCC).

Major finding: ICIs vs standard care were associated with superior overall survival (hazard ratio [HR], 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and overall response rate (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04).

Study details: Findings are from a meta-analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), including 1,657 patients with unresectable HCC treated with either ICIs (n=985) or standard care (n=672).

Disclosures: No source of funding was identified. The lead author and JPS Vasconcelos received grants and/or personal fees from various pharmaceutical companies.

Source: Jácome AA et al. JAMA Netw Open. 2021 Dec 6. doi: 10.1001/jamanetworkopen.2021.36128.

 

Key clinical point: Treatment with immune checkpoint inhibitors (ICIs) was associated with prolonged survival and better safety compared with standard care in patients with unresectable hepatocellular carcinoma (HCC).

Major finding: ICIs vs standard care were associated with superior overall survival (hazard ratio [HR], 0.75; P = .006), progression-free survival (HR, 0.74; P = .03), and overall response rate (odds ratio [OR], 2.82; P < .001) and lower odds of grade 3 or 4 treatment-related adverse events (OR, 0.44; P = .04).

Study details: Findings are from a meta-analysis of 3 randomized controlled trials (KEYNOTE-240, CheckMate-459, and IMbrave150), including 1,657 patients with unresectable HCC treated with either ICIs (n=985) or standard care (n=672).

Disclosures: No source of funding was identified. The lead author and JPS Vasconcelos received grants and/or personal fees from various pharmaceutical companies.

Source: Jácome AA et al. JAMA Netw Open. 2021 Dec 6. doi: 10.1001/jamanetworkopen.2021.36128.

 

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TARE may substitute surgical resection for initial treatment of large single nodular HCC

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Key clinical point: The better safety profile of transarterial radioembolization (TARE) together with comparable efficacy makes it a potential therapeutic alternative to surgical resection for large single nodular hepatocellular carcinoma (HCC).

Main finding: After inverse probability weighting, TARE vs surgical resection achieved similar overall survival (hazard ratio [HR], 0.98; P = .97), time to progression (HR, 1.10; P = .80), and time to intrahepatic progression (HR, 1.45; P = .30), along with a shorter hospital stay (3 days vs 12 days; P < .001) and lower patient proportion experiencing adverse events requiring intervention (0.0% vs 3.2%; P = .39).

Study details: Findings are from a retrospective cohort study including 557 adult patients with single nodular HCC measuring 5 cm who underwent either surgical resection (n=500) or TARE (n=57) shortly after diagnosis.

Disclosures: The authors reported no source of funding. Some of the authors received lecture fees or research grants from various sources.

Source: Kim J et al. J Nucl Med. 2021 Dec 9. doi: 10.2967/jnumed.121.263147.

 

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Key clinical point: The better safety profile of transarterial radioembolization (TARE) together with comparable efficacy makes it a potential therapeutic alternative to surgical resection for large single nodular hepatocellular carcinoma (HCC).

Main finding: After inverse probability weighting, TARE vs surgical resection achieved similar overall survival (hazard ratio [HR], 0.98; P = .97), time to progression (HR, 1.10; P = .80), and time to intrahepatic progression (HR, 1.45; P = .30), along with a shorter hospital stay (3 days vs 12 days; P < .001) and lower patient proportion experiencing adverse events requiring intervention (0.0% vs 3.2%; P = .39).

Study details: Findings are from a retrospective cohort study including 557 adult patients with single nodular HCC measuring 5 cm who underwent either surgical resection (n=500) or TARE (n=57) shortly after diagnosis.

Disclosures: The authors reported no source of funding. Some of the authors received lecture fees or research grants from various sources.

Source: Kim J et al. J Nucl Med. 2021 Dec 9. doi: 10.2967/jnumed.121.263147.

 

Key clinical point: The better safety profile of transarterial radioembolization (TARE) together with comparable efficacy makes it a potential therapeutic alternative to surgical resection for large single nodular hepatocellular carcinoma (HCC).

Main finding: After inverse probability weighting, TARE vs surgical resection achieved similar overall survival (hazard ratio [HR], 0.98; P = .97), time to progression (HR, 1.10; P = .80), and time to intrahepatic progression (HR, 1.45; P = .30), along with a shorter hospital stay (3 days vs 12 days; P < .001) and lower patient proportion experiencing adverse events requiring intervention (0.0% vs 3.2%; P = .39).

Study details: Findings are from a retrospective cohort study including 557 adult patients with single nodular HCC measuring 5 cm who underwent either surgical resection (n=500) or TARE (n=57) shortly after diagnosis.

Disclosures: The authors reported no source of funding. Some of the authors received lecture fees or research grants from various sources.

Source: Kim J et al. J Nucl Med. 2021 Dec 9. doi: 10.2967/jnumed.121.263147.

 

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