المؤلفون: Merle, Philippe, Kudo, Masatoshi, Edeline, Julien, Bouattour, Mohamed, Cheng, Ann-Lii, Chan, Stephen, Yau, Thomas, Garrido, Marcelo, Knox, Jennifer, Daniele, Bruno, Breder, Valeriy, Lim, Ho Yeong, Ogasawara, Sadahisa, Cattan, Stéphane, Chao, Yee, B. Siegel, Abby, Martinez-Forero, Iván, Wei, Ziwen, Liu, C, Finn, Richard

المساهمون: Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Kindai University, Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), National Taïwan University (NTU), The Chinese University of Hong Kong Hong Kong (CUHK), The University of Hong Kong (HKU), Pontificia Universidad Católica de Chile (UC), University of Toronto, N.N. Blokhin National Medical Research Center of Oncology, Sungkyunkwan University Suwon (SKKU), Chiba University, Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille), Pharmaceutical Sciences, Merck & Co. Inc., Merck Research laboratories, Merck Sharp and Dohme (Merck & Co. Inc)-Merck Sharp and Dohme (Merck & Co. Inc), University of California Los Angeles (UCLA), University of California (UC)

المصدر: ISSN: 2235-1795.

مصطلحات موضوعية: Pembrolizumab, Medicine, Placebo, Sorafenib, Internal medicine, Clinical endpoint, Randomization, Gastroenterology, Hepatocellular carcinoma, Randomized controlled trial, Oncology, Cancer, Immunotherapy, Pathology, Alternative medicine, [SDV.CAN]Life Sciences [q-bio]/Cancer

الوصف: International audience ; Introduction: KEYNOTE-240 showed a favorable benefit/risk profile for pembrolizumab versus placebo in patients with sorafenib-treated advanced hepatocellular carcinoma (HCC); however, prespecified statistical significance criteria for overall survival (OS) and progression-free survival (PFS) superiority were not met at the final analysis. Outcomes based on an additional 18 months of follow-up are reported. Methods: Adults with sorafenib-treated advanced HCC were randomized 2:1 to pembrolizumab 200 mg intravenously every 3 weeks or placebo. Dual primary endpoints were OS and PFS assessed per RECIST v1.1 by blinded independent central review (BICR). Secondary endpoints included objective response rate (ORR), assessed per RECIST v1.1 by BICR, and safety. Results: 413 patients were randomized (pembrolizumab, n = 278; placebo, n = 135). As of July 13, 2020, median (range) time from randomization to data cutoff was 39.6 (31.7–48.8) months for pembrolizumab and 39.8 (31.7–47.8) months for placebo. Estimated OS rates (95% CI) were 17.7% (13.4–22.5%) for pembrolizumab and 11.7% (6.8–17.9%) for placebo at 36 months. The estimated PFS rate (95% CI) for pembrolizumab was 8.9% (5.3–13.6%) and 0% for placebo at 36 months. ORR (95% CI) was 18.3% (14.0–23.4%) for pembrolizumab and 4.4% (1.6–9.4%) for placebo. Immune-mediated hepatitis events did not increase with follow-up. No viral hepatitis flare events were reported. Conclusion: With extended follow-up, pembrolizumab continued to maintain improvement in OS and PFS and was associated with a consistent adverse event profile compared with placebo in patients with sorafenib-treated advanced HCC. Although KEYNOTE-240 did not meet prespecified statistical significance criteria at the final analysis, these results together with the antitumor activity of second-line pembrolizumab observed in KEYNOTE-224 and the statistically significant and clinically meaningful OS and PFS benefits of second-line pembrolizumab in patients from Asia observed in KEYNOTE-394 ...

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/37901200; hal-04265920; https://hal.science/hal-04265920Test; https://hal.science/hal-04265920/documentTest; https://hal.science/hal-04265920/file/000529636.pdfTest; PUBMED: 37901200

الإتاحة: https://doi.org/10.1159/000529636Test
https://hal.science/hal-04265920Test
https://hal.science/hal-04265920/documentTest
https://hal.science/hal-04265920/file/000529636.pdfTest

المؤلفون: Chouik, Yasmina, Erard, Domitille, Demian, Hassan, Schulz, Thomas, Mazard, Tessa, Hartig-Lavie, Kerstin, Antonini, Teresa, Mabrut, Jean‐yves, Mohkam, Kayvan, Rode, Agnès, Merle, Philippe

المساهمون: Service d'Hépatologie Hôpital de la Croix-Rousse - HCL, Hôpital de la Croix-Rousse CHU - HCL, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard Lyon -Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL)

المصدر: ISSN: 1664-3224.

مصطلحات موضوعية: immunotherapy, case-report, liver transplantation, Atezolizumab, complete response, Bevacizumab, hepatocellular carcinoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology

الوصف: International audience ; Background: Atezolizumab plus Bevacizumab combination therapy has recently emerged as the new standard of care for unresectable HCC. Significant tumor burden reduction can be observed under that treatment, raising the question of liver transplantation (LT). The safety of another immune checkpoint inhibitor (ICI), nivolumab, is unclear in the pre-transplant setting.Method: We report the case of a 57-y old man, with initial unresectable multinodular HCC contraindicated to LT and locoregional therapies, who achieves complete tumor response after Atezolizumab/Bevacizumab, and subsequently underwent LT for liver failure.Results: Explant analysis revealed complete pathological response with no tumor remnant. The patient suffered from several post-operative complications but no HCC recurrence or biopsy-proven acute rejection occurred 10 months after LT.Conclusions: Atezolizumab/Bevacizumab therapy may enable complete pathological response of advanced HCC. Safety of prolonged treatment need to be assessed.

العلاقة: hal-04161261; https://hal.science/hal-04161261Test; https://hal.science/hal-04161261/documentTest; https://hal.science/hal-04161261/file/fimmu-14-1205997.pdfTest

الإتاحة: https://doi.org/10.3389/fimmu.2023.1205997Test
https://hal.science/hal-04161261Test
https://hal.science/hal-04161261/documentTest
https://hal.science/hal-04161261/file/fimmu-14-1205997.pdfTest

المؤلفون: Nguyen-Khac, Eric, Nahon, Pierre, Ganry, Olivier, Ben Khadhra, Hajer, Merle, Philippe, Amaddeo, Giuliana, Ganne-Carrie, Nathalie, Silvain, Christine, Peron, Jean-Marie, Mathurin, Philippe, Anty, Rodolphe, Uguen, Thomas, Decaens, Thomas, Riachi, Ghassan, Bouattour, Mohamed, Baron, Aurore, Bronowicki, Jean-Pierre, Pageaux, Georges-Philippe, Rosmorduc, Olivier, Ducournau, Gérard, Gilberg, Mélinda, Tanang, Alexandre, Dupin, Julien, Gilbert-Marceau, Anika, Blanc, Jean-Frédéric

المساهمون: Université de Lille, Inserm, CHU Lille, CHU Amiens-Picardie, Université Sorbonne Paris Cité USPC, Hospices Civils de Lyon HCL, Hôpital Henri Mondor, Centre hospitalier universitaire de Poitiers = Poitiers University Hospital CHU de Poitiers, Centre Hospitalier Universitaire de Toulouse CHU Toulouse, Centre Hospitalier Régional Universitaire CHU Lille CHRU Lille, Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286, Université Côte d'Azur UniCA, Centre Hospitalier Universitaire de Rennes CHU Rennes = Rennes University Hospital Ponchaillou, CHU Rouen, Hôpital Beaujon AP-HP, Centre Hospitalier Sud Francilien, Centre Hospitalier Universitaire de Nancy CHU Nancy, CHU Montpellier, Hôpital Paul Brousse, Roche France, CHU Bordeaux

مصطلحات موضوعية: epidemiology, immunotherapy, liver cancer, real-world evidence, targeted therapy

الوصف: Background and objectives Hepatocellular carcinoma epidemiological data are limited in France. The Epidemio Liver Immunotherapy Tecentriq outcome research (ELITor) retrospective study, based on real-world data from the Carcinome HépatocellulaIrE en France (CHIEF) French cohort of hepatocellular carcinoma patients, aimed to get insight into the treatment patterns, the sociodemographic, clinical, biological, and etiological characteristics, and the quality of life of patients with unresectable hepatocellular carcinoma. Methods and results Between 1 September 2019 and 4 December 2020, 367 patients from the CHIEF cohort received at least one locoregional (52.8%) chemoembolization or radioembolization or systemic treatment (88.3%) and were selected for ELITor. Most patients had a Barcelona Clinic Liver Cancer (BCLC) C (93.2%) hepatocellular carcinoma stage and were affected by cirrhosis (67.7%). Alcohol was confirmed as the main etiology both as a single etiology (29.1%) and in association with other risk factors (26.9%), mainly metabolic disorders (16.2%). Tyrosine-kinase inhibitors, mainly sorafenib, were the most administered systemic treatments in first line. Patients who received at least one combination of atezolizumab and bevacizumab during the study period (N = 53) had a better performance status and less portal hypertension frequency than the overall population and more hepatitis B virus infection and fewer metabolic disorders as single etiology. Overall, the global health score before treatment (62.3 ± 21.9) was in line with that of reference cancer patients and worsened in 51.9% of the cases after first-line palliative-intent treatment. Conclusion This study provided real-life data on advanced hepatocellular carcinoma characteristics and treatment patterns and described the first patients to receive the atezolizumab-bevacizumab combination before it became the new standard of care for advanced hepatocellular carcinoma.

العلاقة: European Journal of Gastroenterology & Hepatology; Eur J Gastroenterol Hepatol; http://hdl.handle.net/20.500.12210/105975Test

الإتاحة: https://doi.org/20.500.12210/105975Test
https://hdl.handle.net/20.500.12210/105975Test

المؤلفون: Ren, Zhenggang, Ducreux, Michel, Abou-Alfa, Ghassan K, Merle, Philippe, Fang, Weijia, Edeline, Julien, Li, Zhiwei, Wu, Lihua, Assenat, Eric, Hu, Sheng, Rimassa, Lorenza, Zhang, Tao, Blanc, Jean-Frederic, Pan, Hongming, Ross, Paul, Yen, Chia-Jui, Tran, Albert, Shao, Guoliang, Bouattour, Mohamed, Chen, Yajin, Meyer, Tim, Hou, Jinlin, Tougeron, David, Bai, Yuxian, Hou, Ming-Mo, Meng, Zhiqiang, Wu, John, Li, Vincent, Chica-Duque, Sandra, Cheng, Ann-Lii

المصدر: Liver Cancer (2022) (In press).

مصطلحات موضوعية: Tislelizumab, Hepatocellular carcinoma, Immunotherapy, Pretreated patient population

الوصف: Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multi-regional phase 2 study, RATIONALE-208, examined single-agent tislelizumab (200 mg intravenously every three weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018 and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9–18), including five complete and 27 partial responses. Number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8–20]; two or more prior lines, 13% [95% CI, 7–20]). Median duration of response was not reached. Disease control rate was 53% and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC.

وصف الملف: application/pdf

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10161827/1/527175.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10161827Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10161827/1/527175.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10161827Test/

المؤلفون: Roth, Gael S., Villeret, François, Decaens, Thomas, Merle, Philippe, Nahon, Pierre

المصدر: Liver International; Mar2023, Vol. 43 Issue 3, p546-557, 12p, 1 Diagram, 2 Charts

مصطلحات موضوعية: LIVER diseases, HEPATOCELLULAR carcinoma, CLINICAL trials, ETIOLOGY of diseases, IMMUNOTHERAPY

مستخلص: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide, with up to 90% of HCC cases occurring in the setting of underlying cirrhosis. Therapeutic landscape for advanced HCC has dramatically changed in recent years with the advent of immunotherapy, including several combinations. Data suggest that the surrounding liver milieu may influence tumour response. In addition, different aetiologies of HCC and their effects on the host liver may impact response to immunotherapy. However, to date, guidelines do not take into account this parameter to guide therapeutic selection, and phase III trials are likewise performed in patients irrespective of HCC aetiology. Moreover, most clinical trial data are collected in highly selected patients with preserved liver function (defined as Child‐Pugh class A) and controlled portal hypertension, which does not accurately reflect routine clinical practice. In this review, we discuss the influence of liver disease aetiology on the response to immunotherapy in patients with advanced HCC. We also discuss the safety and efficacy of various immunotherapeutic agents in Child‐Pugh B patients to determine if these treatments are beneficial in this vulnerable patient population. [ABSTRACT FROM AUTHOR]

: Copyright of Liver International is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Ren, Zhenggang, Ducreux, Michel, Abou-Alfa, Ghassan K., Merle, Philippe, Fang, Weijia, Edeline, Julien, Li, Zhiwei, Wu, Lihua, Assenat, Eric, Hu, Sheng, Rimassa, Lorenza, Zhang, Tao, Blanc, Jean-Frédéric, Pan, Hongming, Ross, Paul, Yen, Chia-Jui, Tran, Albert, Shao, Guoliang, Bouattour, Mohamed, Chen, Yajin

المصدر: Liver Cancer (2235-1795); 2023, Vol. 12 Issue 1, p72-84, 13p

مصطلحات موضوعية: HEPATOCELLULAR carcinoma, ADVERSE health care events, TERMINATION of treatment, LIVER cancer

مستخلص: Introduction: Tislelizumab (anti-programmed cell death protein 1 antibody) showed preliminary antitumor activity and tolerability in patients with advanced solid tumors, including hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of tislelizumab in patients with previously treated advanced HCC. Methods: The multiregional phase 2 study RATIONALE-208 examined single-agent tislelizumab (200 mg intravenously every 3 weeks) in patients with advanced HCC with Child-Pugh A, Barcelona Clinic Liver Cancer stage B or C, and who had received one or more prior lines of systemic therapy. The primary endpoint was objective response rate (ORR), radiologically confirmed per Response Evaluation Criteria in Solid Tumors version 1.1 by the Independent Review Committee. Safety was assessed in patients who received ≥1 dose of tislelizumab. Results: Between April 9, 2018, and February 27, 2019, 249 eligible patients were enrolled and treated. After a median study follow-up of 12.7 months, ORR was 13% (n = 32/249; 95% confidence interval [CI], 9–18), including five complete and 27 partial responses. The number of prior lines of therapy did not impact ORR (one prior line, 13% [95% CI, 8–20]; two or more prior lines, 13% [95% CI, 7–20]). Median duration of response was not reached. The disease control rate was 53%, and median overall survival was 13.2 months. Of the 249 total patients, grade ≥3 treatment-related adverse events were reported in 38 (15%) patients; the most common was liver transaminase elevations in 10 (4%) patients. Treatment-related adverse events led to treatment discontinuation in 13 (5%) patients or dose delay in 46 (19%) patients. No deaths were attributed to the treatment per investigator assessment. Conclusion: Tislelizumab demonstrated durable objective responses, regardless of the number of prior lines of therapy, and acceptable tolerability in patients with previously treated advanced HCC. [ABSTRACT FROM AUTHOR]

: Copyright of Liver Cancer (2235-1795) is the property of Karger AG and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Ryoo, Baek‐Yeol¹ (AUTHOR), Merle, Philippe² (AUTHOR), Kulkarni, Amit S.³ (AUTHOR), Cheng, Ann‐Lii⁴ (AUTHOR), Bouattour, Mohamed⁵ (AUTHOR), Lim, Ho Yeong⁶ (AUTHOR), Breder, Valeriy⁷ (AUTHOR), Edeline, Julien⁸ (AUTHOR), Chao, Yee⁹ (AUTHOR), Ogasawara, Sadahisa¹⁰ (AUTHOR), Yau, Thomas¹¹ (AUTHOR), Garrido, Marcelo¹² (AUTHOR), Chan, Stephen L.¹³ (AUTHOR), Daniele, Bruno¹⁴ (AUTHOR), Norquist, Josephine M.³ (AUTHOR), Chen, Erluo³ (AUTHOR), Siegel, Abby B.³ (AUTHOR), Zhu, Andrew X.^15,16 (AUTHOR), Finn, Richard S.¹⁷ (AUTHOR), Kudo, Masatoshi¹⁸ (AUTHOR) m-kudo@med.kindai.ac.jp

المصدر: Cancer (0008543X). Mar2021, Vol. 127 Issue 6, p865-874. 10p.

مصطلحات موضوعية: *DRUG efficacy, *PEMBROLIZUMAB, *QUALITY of life, *SORAFENIB

مستخلص: Background: Health‐related quality of life (HRQoL) is an important outcome measure and prognostic indicator in hepatocellular carcinoma (HCC). KEYNOTE‐240 (NCT02702401) assessed the efficacy and safety of pembrolizumab plus best supportive care (BSC) versus placebo plus BSC in patients with HCC who previously received sorafenib. This study presents the results of a prespecified exploratory analysis of patient‐reported outcomes. Methods: Patients completed the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ‐C30) and its HCC supplement (EORTC QLQ‐HCC18) electronically at baseline; at weeks 2, 3, 4, 6, 9, 12, and 18; and then every 9 weeks until 1 year or end of treatment, and at the 30‐day safety follow‐up visit. Results: The HRQoL population included 271 and 127 patients randomly assigned to pembrolizumab and placebo, respectively. From baseline to week 12, changes in both scores were similar between pembrolizumab and placebo; global health status/QoL scores were stable. The proportions of patients who improved, remained stable, or deteriorated across all functional domain and symptom scores were generally similar between pembrolizumab and placebo. Time to deterioration was similar between the 2 arms based on the prespecified analysis of EORTC QLQ‐HCC18 domains of abdominal swelling, fatigue, and pain. Conclusion: Pembrolizumab preserved HRQoL during treatment for advanced HCC. Combined with efficacy and safety results from KEYNOTE‐240, these findings support a positive benefit/risk profile for pembrolizumab in a second‐line treatment setting for patients with HCC who previously received sorafenib. Pembrolizumab preserves health‐related quality of life during treatment in patients with advanced hepatocellular carcinoma (HCC) who had progression during or after or were intolerant to sorafenib. The results of this prespecified exploratory analysis combined with efficacy and safety data from KEYNOTE‐240 support a favorable risk–benefit profile for pembrolizumab in a second‐line treatment setting for patients with HCC who previously received sorafenib. [ABSTRACT FROM AUTHOR]

المؤلفون: Merle, Philippe^1,2,3,4 philippe.merle@inserm.fr

المصدر: Hépato-Gastro & Oncologie Digestive. Supplement 1, Vol. 27, p35-40. 6p.

مستخلص: Résumé: Le carcinome hépatocellulaire avancé ne peut bénéficier que des thérapies systémiques qui, depuis 2007, n'ont été que des inhibiteurs de tyrosines kinases, essentiellement tumorostatiques et avec des effets secondaires notables. L'avènement de l'immuno-oncologie s'est avéré décevant en monothérapie, mais par contre, dans des stratégies de combinaison avec des régulateurs du microenvironnement tumoral, a montré un bénéfice très significatif sur l'efficacité et la qualité de vie des patients. Ces résultats récents vont complètement modifier le paradigme du traitement systémique du carcinome hépatocellulaire. Advanced hepatocellular carcinoma is prone to systemic therapies that have been tyrosine kinase inhibitors since 2007, mainly tumorostatic with poor tolerability. The arising of immuno-oncology has been disappointing in montherapy, but combined to regulators of the tumoral micro-environment, has been successful with striking improvement of efficacy and quality of life of patients. These date are completely modifying the paradigm of HCC therapeutic strategies. [ABSTRACT FROM AUTHOR]

المؤلفون: Merle, Philippe¹ (AUTHOR) philippe.merle@inserm.fr

المصدر: Cancers. Jan2021, Vol. 13 Issue 2, p238-238. 1p.

مصطلحات موضوعية: *THERAPEUTIC use of antineoplastic agents, *ANTINEOPLASTIC agents, *CANCER relapse, *COMBINED modality therapy, *DRUG efficacy, *HEPATOCELLULAR carcinoma, *IMMUNOTHERAPY, *PATIENT safety, *SURVIVAL, *TUMOR markers, *PROTEIN-tyrosine kinase inhibitors, *TREATMENT effectiveness, *DISEASE progression, *IMMUNE checkpoint inhibitors, *THERAPEUTICS

مستخلص: Simple Summary: Hepatocellular carcinoma is a frequent and poor prognosis tumor, with most patients facing up, soon or later, to systemic therapies. So far, systemic therapies based on tyrosine kinase inhibitor monotherapies have been of modest benefit. The aim of this review article was to characterize the profile of efficacy and safety of immuno-oncology-based monotherapies that failed to demonstrate significant benefit, for comparison with the immuno-oncology-based combinational strategies. One of them has proven its drastic benefit in phase-3, whereas others have only shown promising data in phase-1/2, although the corresponding phase-3 results are pending. We showed that objective response rates and duration of response are important parameters for increased median overall survival and long survivals. We also pointed out that, being aware that there is an urgent unmet need for biomarkers, the pattern of safety and quality of life will guide the physician for the choice on the possible future combinations. Hepatocellular carcinoma is a poor prognosis tumor. Systemic therapies are frequently used due to frequent recurrences after surgical or radiologic treatments. Anti-angiogenic tyrosine kinase inhibitors have shown efficacy in monotherapy, but with very low rates of long survival and exceptional recovery. Immuno-oncology based on immune checkpoint inhibitors has revolutionized the systemic therapies since showing long survival rates without any tumor progression or recurrence for some patients in partial or complete response, and possibly for some patients in stable disease. However, the rate of responders under immuno-oncology monotherapy is too low to increase significantly the median overall survival of the treated patients. The immuno-oncology-based combinations with different types of immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 inhibitors such as nivolumab, pembrolizumab, atezolizumab, durvalumab, ipilimumab, tremelimumab), or the association of immune checkpoint inhibitors plus anti-angiogenic agents (bevacizumab, lenvatinib, cabozantinib), have led to a breakthrough in the treatment of hepatocellular carcinoma. Indeed, the first phase-3 trial, combining atezolizumab with bevacizumab, has dramatically changed the outcome of patients. Data from several other types of combinations assessed in phase-3 trials are pending, and if positive, will drastically arm the physicians to efficiently treat the patients, and disrupt the current algorithm of hepatocellular carcinoma treatment. [ABSTRACT FROM AUTHOR]