scholarly journals Immunotherapy in Hepatocellular Carcinoma: Is There a Light at the End of the Tunnel?

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1078 ◽  
Author(s):  
Amit Mahipal ◽  
Sri Harsha Tella ◽  
Anuhya Kommalapati ◽  
Alexander Lim ◽  
Richard Kim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Progression Free Survival ◽  
The United States ◽  
Hepatic Reserve ◽  
Dismal Prognosis ◽  
United States Food

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with dismal prognosis when diagnosed at advanced stages. Surgical resection of the primary tumor or orthotropic liver transplantation serves as a potential curative option. However, this approach is highly dependent on the hepatic reserve and baseline functional status of the patient. Liver directed therapies such as portal vein embolization (PVE), trans-arterial chemoembolization (TACE), and systemic chemotherapy are employed in non-surgical candidates. Sorafenib was the only approved systemic therapeutic agent for almost a decade until the recent approval of lenvatinib by the United States Food and Drug Administration (FDA) as an alternate first-line agent. Regorafenib, nivolumab, pembrolizumab and cabozantinib are approved by the FDA as second-line agents in patients who failed or could not tolerate sorafenib. Ramucirumab was recently FDA approved for the subset of patients that have high alfa-fetoprotein levels (>400 ng/mL). A better understanding of tumorigenesis and encouraging clinical trial results that evaluated immune-checkpoint inhibitors opened doors for immunotherapy in HCC. Immune checkpoint inhibitors have demonstrated a prolonged median overall and progression-free survival in a subset of patients with HCC. On-going translational and clinical research will hopefully provide us with a better understanding of tumor markers, genetic aberrations and other factors that determine the immunotherapy response in HCC. In this review, we sought to summarize the potential role and future directions of immunotherapy in the management of HCC.

scholarly journals Emerging role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 698 ◽  
Author(s):  
Longo ◽  
Brunetti ◽  
Gnoni ◽  
Licchetta ◽  
Delcuratolo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Single Agent ◽  
First Line ◽  
Dismal Prognosis ◽  
Programmed Death

Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70–80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib had been the standardcare for almost a decade until 2018 when the Food and Drug Administration approved an alternative first-line agent namely lenvatinib. Cabozantinib, regorafenib, and ramucirumab also displayed promising results in second line settings. FOLFOX4, however, results inan alternative first-line treatment for the Chineseclinical oncology guidelines. Moreover,nivolumab and pembrolizumab,two therapeutics against the Programmed death (PD)-ligand 1 (PD-L1)/PD1 axis have been recently approvedfor subsequent-line therapy. However, similar to other solid tumors, the response rate of single agent targeting PD-L1/PD1 axis is low. Therefore, a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors (ICIs), the addition of ICIs after resection or during loco-regional therapy, ICIs in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with a careful assessmentof new ICIs-based combinatory approaches.

scholarly journals Emerging Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

2019 ◽  
Author(s):  
Vito Longo ◽  
Oronzo Brunetti ◽  
Antonio Gnoni ◽  
Antonella Licchetta ◽  
Sabina Del Curatolo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Liver Cancer ◽  
Single Agent ◽  
Locoregional Therapy ◽  
First Line ◽  
Dismal Prognosis

Hepatocellular carcinoma is the most common primary liver cancer and the fourth leading cause of cancer death worldwide. A total of 70-80% of patients are diagnosed at an advanced stage with a dismal prognosis. Sorafenib has been the standard of care for almost a decade until 2018 when FDA approved an alternative first-line agent namely lenvatinib. Whereas FOLFOX4 results an alternative first-line treatment for the chinese clinical oncology guidelines. In addition to cabozantinib, regorafenib, and ramucirumab, two therapeutics against the PD-L1/PD1 axis have been recently approved for subsequent-line therapy, as nivolumab and pembrolizumab. However, similar to other solid tumors, the response rate of single-agent targeting PD-L1/PD1 axis is low. Therefore a lot of combinatory approaches are under investigation, including the combination of different immune checkpoint inhibitors, the addition of immune checkpoint inhibitors after resection or during locoregional therapy, immune checkpoint inhibitors in addition to kinase inhibitors, anti-angiogenic therapeutics, and others. This review focuses on the use of ICIs for the hepatocellular carcinoma with an attent evaluation of new ICIs based combinatory approaches.

scholarly journals Lenvatinib Plus Immune Checkpoint Inhibitors Improve Survival in Advanced Hepatocellular Carcinoma: A Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaozhun Huang ◽  
Lin Xu ◽  
Teng Ma ◽  
Xin Yin ◽  
Zhangkan Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
New Strategy

BackgroundNivolumab and pembrolizumab disrupt the programmed cell death-1 immune checkpoint and display promising efficacy and safety results in advanced hepatocellular carcinoma (HCC). However, the benefits remain limited. The preliminary results of lenvatinib (LEN) combined with immune checkpoint inhibitors (ICIs) reveal that the combinations were well-tolerated and encouraging. This study aimed to analyze the safety and efficacy of LEN plus ICIs in a real-world cohort of patients with advanced HCC.MethodBetween June 4, 2017, and June 30, 2019, 16 patients received LEN plus nivolumab, and 13 patients were treated with LEN plus pembrolizumab, with the confirmed advanced HCC retrospectively analyzed. The clinical parameters, as well as the outcomes, were assessed.ResultsAll the patients had Barcelona Clinical Liver Cancer Stage C. LEN with ICIs was used as systemic second-, third-, and fourth-line treatments in seven (24.1%), 14 (48.3%), and eight (27.6%) patients, respectively. At the time of data cutoff, six patients (37.5%) were still receiving LEN with nivolumab, while another six patients (46.2%) were still receiving LEN with pembrolizumab. An objective response was recorded in seven patients (25.9%), while the best overall responses were from one complete response and six partial responses. The 6- and 12-month over survival (OS) rates were 62.6% and 53.7%, respectively. Furthermore, the 6- and 12-month progression-free survival (PFS) rates were 43.5% and 31.8%, respectively. In the subgroup analyses, the 6- and 12-month OS and PFS rates for patients treated with LEN plus nivolumab were 62.5% and 52.1%, respectively, and 43.8% and 30.0%, respectively. The 6- and 12-month OS and PFS rates for patients treated with LEN plus pembrolizumab were 51.3% and 51.3%, respectively, and 49.2% and 49.2%, respectively. A total of 11 (31%) deaths were reported in this study, four of which were attributed to grade 5 adverse events presented as fatal treatment-related hepatitis.ConclusionThe combination of LEN and ICIs is a promising new strategy for the treatment of HCC patients. However, high-grade hepatic toxicity was observed and further evaluation of this combination is still required.

scholarly journals Efficacy and Safety of TACE Combined With Sorafenib Plus Immune Checkpoint Inhibitors for the Treatment of Intermediate and Advanced TACE-Refractory Hepatocellular Carcinoma: A Retrospective Study

2021 ◽  
Vol 7 ◽  
Author(s):  
Liyun Zheng ◽  
Shiji Fang ◽  
Fazong Wu ◽  
Weiqian Chen ◽  
Minjiang Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Factors Affecting ◽  
Pugh Class

Purpose: The study aims to retrospectively investigate the efficacy and safety of sorafenib combined with transarterial chemoembolization (TACE) (TACE+Sor) vs. TACE combined with sorafenib plus immune checkpoint inhibitors (TACE+Sor+ICIs) in treating intermediate and advanced TACE-refractory hepatocellular carcinoma (HCC).Materials and Methods: This study was approved by the ethics committee of Lisui Hospital, Zhejiang University, China. From January 2016 to June 2020, 51 eligible patients with intermediate or advanced TACE-refractory HCC received TACE+Sor (n = 29) or TACE+Sor+ICIs (n = 22). The differences in tumor response, adverse events (AEs), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Factors affecting PFS and OS were determined by Cox regression.Results: The disease control rate was higher in the TACE+Sor+ICIs group than in the TACE+Sor group (81.82 vs. 55.17%, P = 0.046). Compared with the TACE+Sor group, PFS and OS were prolonged in the TACE+Sor+ICIs group (median PFS: 16.26 vs. 7.30 months, P < 0.001; median OS: 23.3 vs. 13.8 months, P = 0.012). Multivariate analysis showed that BCLC stage, alpha-fetoprotein and treatment were independent factors of PFS; BCLC, Child-Pugh class, ablation after disease progression and treatment were independent predictive factors of OS. Four patients in the TACE+Sor+ICIs group and three patients in the TACE+Sor group suffered from dose reduction or interruption (18.18 vs. 10.34%, P = 0.421). The incidence of ICI-related AEs in the TACE+Sor+ICIs group was well-controlled.Conclusion: The therapeutic schedule of TACE+Sor+ICIs demonstrated efficacy and safety in intermediate and advanced TACE-refractory HCC.

scholarly journals Correlation Between Immune-Related Adverse Events and Prognosis in Hepatocellular Carcinoma Patients Treated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuo Xu ◽  
Ruixue Lai ◽  
Qian Zhao ◽  
Pandong Zhao ◽  
Ruili Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Low Grade ◽  
Better Than

BackgroundImmune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) were associated with clinical benefit in cancer patients of melanoma, a lung cancer. In the present study, we investigated the correlation between irAE and ICI efficacy in hepatocellular carcinoma (HCC) patients.MethodsWe divided the HCC patients who received the anti-PD-1 antibody into two groups as irAE group and non-irAE group according to the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. The treatment efficacy of ICIs was evaluated with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).ResultOf the 65 HCC patients who received the anti-PD-1 antibody (monotherapy or combined with targeted medicine), median PFS in the irAE group was superior to that in the non-irAE group (302 days vs. 148 days, p = 0.004). Median OS in the irAE group was also better than that in the non-irAE group (374 days vs. 279 days, p = 0.038). Although the statistical difference for DCR in the irAE group and non-irAE group was not reached, the DCR of the irAE displayed a trend better than that of the non-irAE group (41.20% vs. 20.80%, p = 0.118). Multivariate analysis also demonstrated that the non-irAE group (HR = 6.410, 95% CI: 1.404 to 29.275) was associated independently with the poor prognosis.ConclusionsDevelopment of irAEs was associated with clinical benefit for HCC patients who were treated with immune checkpoint inhibitors; irAE, particularly low-grade irAE, was a predictable marker for better ICI treatment efficiency in HCC patients.

Treatment-related toxicity and improved outcomes with immune checkpoint inhibitors in patients with hepatocellular carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4085-4085
Author(s):  
Alessio Cortellini ◽  
Thomas Urban Marron ◽  
Pallavi Shruti Mishra-Kalyani ◽  
Yutao Gong ◽  
Anwaar Saeed ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Tertiary Care ◽  
Unmet Need ◽  
Tumour Response ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Duration Of Treatment

4085 Background: The development of treatment-related adverse events (trAE) correlates favorably with clinical outcomes in multiple studies of patients receiving immune checkpoint inhibitors (ICI), however, this relationship is undefined in patients with hepatocellular carcinoma (HCC). This retrospective multi-center study aimed to examine whether trAEs are prognostic in HCC. Methods: We established an international consortium of 10 tertiary-care referral centers located in Europe (n = 67), United States (US, n = 248) and Asia (n = 42) to test whether the development of clinically significant trAE (i.e. graded >2, trAE2) predicted for improved overall (OS), progression-free survival (PFS), and overall response rates (ORR) following ICI, and subsequently validated this association in a separate cohort of 406 HCC patients receiving ICI therapy as part of international clinical trials submitted to the US Food and Drug Administration (FDA) in support of marketing applications. Results: In a multi-institutional cohort of 357 patients, 274 (77%) with Barcelona Clinic Liver Cancer (BCLC) stage C HCC mostly treated with ICI monotherapy (n = 304, 85%), trAE were reported in 146 patients (41%). Development of trAE2 were associated with longer OS (23.3 versus 12.2 months) and PFS (8.6 months versus 3.7 months). After adjusting for viral aetiology, gender, presence of cirrhosis, Child-Pugh class, BCLC stage, AFP levels, ECOG-PS, ICI regimen (mono/combination therapy) and receipt of corticosteroid therapy, trAE2 were confirmed predictors of improved OS (HR 0.55; 95%CI:0.34-0.88) and PFS (HR 0.51; 95%CI: 0.35-0.74). TrAE2 were associated with higher ORR (27% versus 16%) from ICI. The association between trAE2 and patients’ OS (HR 0.49; 95%CI:0.34-0.70) and PFS (HR 0.43; 95%CI:0.32-0.59) was also observed in the FDA dataset. After a 6-weeks landmark selection, trAE2 were confirmed to be associated with improved PFS (HR 0.59; 95%CI:0.39-0.87); the additional analysis adjusted for tumour response and duration of treatment within the FDA cohort further confirmed the association with longer PFS (HR 0.67; 95%CI: 0.47-0.94). Conclusions: Development of trAE2 may correlate with response and survival in patients with HCC receiving ICI, a clinical setting where the lack of biomarkers still represents an unmet need. Prospective studies aimed at understanding the underlying immunologic foundations of such relationship are warranted to identify predictive biomarkers of toxicity and response.

Immune checkpoint and checkpoint inhibitors in hepatocellular carcinoma

2018 ◽  
Vol 1 (1) ◽  
pp. 28-32
Author(s):  
Piyawat Komolmit
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell Receptor ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cell Receptor ◽  
Immune Checkpoints ◽  
Histocompatibility Complex

การรักษามะเร็งด้วยแนวความคิดของการกระตุ้นให้ภูมิต้านทานของร่างกายไปทำลายเซลล์มะเร็งนั้น ปัจจุบันได้รับการพิสูจน์ชัดว่าวิธีการนี้สามารถหยุดยั้งการแพร่กระจายของเซลล์มะเร็ง โดยไม่ก่อให้เกิดภาวะแทรกซ้อนทางปฏิกิริยาภูมิต้านทานต่ออวัยวะส่วนอื่นที่รุนแรง สามารถนำมาใช้ทางคลินิกได้ ยุคของการรักษามะเร็งกำลังเปลี่ยนจากยุคของยาเคมีบำบัดเข้าสู่การรักษาด้วยภูมิต้านทาน หรือ immunotherapy ยากลุ่ม Immune checkpoint inhibitors โดยเฉพาะ PD-1 กับ CTLA-4 inhibitors จะเข้ามามีบทบาทในการรักษามะเร็งตับในระยะเวลาอันใกล้ จำเป็นแพทย์จะต้องมีความรู้ความเข้าใจในพื้นฐานของ immune checkpoints และยาที่ไปยับยั้งโมเลกุลเหล่านี้ Figure 1 เมื่อ T cells รับรู้แอนทิเจนผ่านทาง TCR/MHC จะมีปฏิกิริยาระหว่าง co-receptors หรือ immune checkpoints กับ ligands บน APCs หรือ เซลล์มะเร็ง ทั้งแบบกระตุ้น (co-stimulation) หรือยับยั้ง (co-inhibition) TCR = T cell receptor, MHC = major histocompatibility complex

The Relationship of Diabetes Mellitus to Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer

Oncology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Oded Jacobi ◽  
Yosef Landman ◽  
Daniel Reinhorn ◽  
Oded Icht ◽  
Michal Sternschuss ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Proportional Hazards ◽  
Checkpoint Inhibitors ◽  
Negative Relationship ◽  
Progression Free Survival ◽  
Significant Negative Correlation ◽  
Cox Proportional Hazards ◽  
Diabetic Patients

<b><i>Introduction:</i></b> Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. <b><i>Methods:</i></b> All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, <i>t</i> tests, and χ<sup>2</sup> tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. <b><i>Results:</i></b> Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01–2.06], <i>p</i> = 0.011, and HR 1.5 [1.08–2.08], <i>p</i> = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61–1.93], <i>p</i> = 0.79, and HR 1.29 [0.69–2.39], <i>p</i> = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. <b><i>Conclusion:</i></b> Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.

scholarly journals How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches

2021 ◽  
Vol 10 (7) ◽  
pp. 1412
Author(s):  
Michele Ghidini ◽  
Angelica Petrillo ◽  
Andrea Botticelli ◽  
Dario Trapani ◽  
Alessandro Parisi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Clinical Implementation ◽  
T Cell Therapy ◽  
Dismal Prognosis

Despite extensive research efforts, advanced gastric cancer still has a dismal prognosis with conventional treatment options. Immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors. Amongst gastric cancer subtypes, tumors with microsatellite instability and Epstein Barr Virus positive tumors provide the strongest rationale for responding to immunotherapy. Various predictive biomarkers such as mismatch repair status, programmed death ligand 1 expression, tumor mutational burden, assessment of tumor infiltrating lymphocytes and circulating biomarkers have been evaluated. However, results have been inconsistent due to different methodologies and thresholds used. Clinical implementation therefore remains a challenge. The role of immune checkpoint inhibitors in gastric cancer is emerging with data from monotherapy in the heavily pre-treated population already available and studies in earlier disease settings with different combinatorial approaches in progress. Immune checkpoint inhibitor combinations with chemotherapy (CT), anti-angiogenics, tyrosine kinase inhibitors, anti-Her2 directed therapy, poly (ADP-ribose) polymerase inhibitors or dual checkpoint inhibitor strategies are being explored. Moreover, novel strategies including vaccines and CAR T cell therapy are also being trialed. Here we provide an update on predictive biomarkers for response to immunotherapy with an overview of their strengths and limitations. We discuss clinical trials that have been reported and trials in progress whilst providing an account of future steps needed to improve outcome in this lethal disease.

scholarly journals Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

2021 ◽  
Vol 9 (2) ◽  
pp. e001945 ◽  
Author(s):  
Jeffrey Sum Lung Wong ◽  
Gerry Gin Wai Kwok ◽  
Vikki Tang ◽  
Bryan Cho Wing Li ◽  
Roland Leung ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Acquired Resistance ◽  
Survival Rates ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Resistance ◽  
Advanced Hcc

BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.ConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.

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