Real-world experience of pembrolizumab plus lenvatinib in unresectable hepatocellular carcinoma in Taiwan.

e16627 Background: Multi-kinase inhibitors and immune checkpoint inhibitors (ICIs) are treatment options of systemic therapy for unresectable hepatocellular carcinoma (HCC). Targeted therapy can potentially enhance T cell infiltration and activation, consequently, cooperate with ICIs to produce synergistic anti-tumor effects. The ongoing clinical trial shows promising data by combining pembrolizumab with lenvatinib for advanced HCC. The study tried to evaluate the treatment response and adverse events of pembrolizumab plus lenvatinib for HCC in real-world setting. Methods: From Jul. 2019, patients who received pembrolizumab plus lenvatinib for unresectable HCC in a tertiary medical center in Taiwan were prospectively enrolled. The status of HCC was either in advanced HCC or failed by prior locoregional treatment. The dosage of pembrolizumab was 100mg every 3 weeks. The starting dose of lenvatinib was 10mg per day then titrating to weight-based dose according to recommendation. Patients who had received at least 2 cycles of pembrolizumab were evaluated in this report. The tumor response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST). The treatment related adverse events (TRAEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Till the end of Jan. 2020, 27 patients had received at least 2 cycles of pembrolizumab, and 17 had evaluable post-treatment images either by CT or MRI. There were 6 (22.2%) in BCLC B, and 21 (77.8%) in BCLC C. Of them, 17 (63%) were treated as the first-line systemic treatment, 8 as the second-line and 2 as the third line systemic treatment. Of the 17 cases with post-treatment image studies, there were 6 (35.3%) in partial response (PR), 7 (41.2%) in stable disease (SD), and 4 (23.5%) in progressive disease (PD) by RECIST v1.1; and 1 (5.8%) in complete response (CR), 9 (52.9%) in PR, 3 (17.6%) in SD and 4 (23.5%) in PD by mRECIST, respectively. The objective response rate (ORR) and disease control rate (DCR) by mRECIST were 58.7% and 76.5%, respectively. The most common TRAEs in any grade were hypertension 24 (88.4%), palmar-plantar syndrome 19 (70.4%), hypothyroidism 19(70.4%). The Grade 3/4 TRAEs were 3 (11.1%) with psoriasis-like skin reaction, 3 (11.1%) with hypertension and 2 (7.4%) with palmar-plantar syndrome. Conclusions: Pembrolizumab plus lenvatinib can produce excellent ORR and DCR with tolerable safety profiles. Such combination could be a promising strategy for unresectable HCC in the future.

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Efficacy and Safety of Lenvatinib Therapy for Unresectable Hepatocellular Carcinoma in a Real-World Practice in Korea

Liver Cancer ◽

10.1159/000512239 ◽

2021 ◽

pp. 1-11

Author(s):

Myung Ji Goh ◽

Joo Hyun Oh ◽

Yewan Park ◽

Jihye Kim ◽

Wonseok Kang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Factors ◽

Disease Progression ◽

Real World ◽

Medical Center ◽

Objective Response ◽

Progression Free Survival ◽

Efficacy And Safety ◽

Eligibility Criteria ◽

Unresectable Hepatocellular Carcinoma

Background: Lenvatinib has been recently approved as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Korea. We aimed to study the efficacy and safety of lenvatinib therapy in a real-world practice and to find prognostic factors related to survival and disease progression. Methods: A hospital-based retrospective study was conducted on 111 consecutive patients who had unresectable HCC and were treated with lenvatinib at Samsung Medical Center from October 2018 to March 2020. Efficacy was determined using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria in 111 patients who completed 1st tumor assessment. Safety was evaluated in 116 HCC patients including 5 patients who discontinued lenvatinib due to adverse events (AEs) before 1st tumor assessment using Common Terminology Criteria for AEs version 5.0. Results: A total of 111 patients with a median age of 59 years were analyzed during a median follow-up duration of 6.2 (4.4–9.0) months. The Kaplan-Meier estimate of overall survival was 10.5 months, and the median progression-free survival was 6.2 months. Based on mRECIST criteria, the objective response rate was 18.9% and disease control rate was 75.7%. AEs developed in 86/116 (74.1%) patients, and grade ≥3 AEs developed in 16/116 (13.8%) patients. Diarrhea, hand-foot skin rash, abdominal pain, hypertension, and anorexia were identified as the AEs with the highest frequencies of any grade. REFLECT eligibility criteria including tumor extent ≥50% liver occupation or inadequate bone marrow function and occurrence of anorexia were prognostic factors for survival, and occurrence of diarrhea was a favorable factor for disease progression. Conclusion: Lenvatinib therapy showed a favorable efficacy and safety in a real-world practice. The REFLECT eligibility criteria and specific AEs could be one of the prognostic markers.

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Efﬁcacy and Safety of Radiotherapy Plus Anti-PD1 Versus Transcatheter Arterial Chemoembolization Plus Sorafenib For Advanced Hepatocellular Carcinoma: a Real-World Study

10.21203/rs.3.rs-1190210/v1 ◽

2021 ◽

Author(s):

Jian-Xu Li ◽

Wen-Xiang Deng ◽

Shi-Ting Huang ◽

Xiao-Feng Lin ◽

Mei-Ying Long ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Real World ◽

Transcatheter Arterial Chemoembolization ◽

Objective Response ◽

Advanced Hepatocellular Carcinoma ◽

Efficacy And Safety ◽

Advanced Hcc ◽

Sorafenib Group ◽

Arterial Chemoembolization

Abstract Background: The combination of transcatheter arterial chemoembolization (TACE) plus sorafenib prolonged progression-free survival (PFS) and overall survival (OS) than sorafenib or TACE monotherapy for patients with hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of radiotherapy (RT) plus monoclonal antibody against programmed cell death 1 (anti-PD1) versus TACE plus sorafenib for patients with advanced HCC.Methods: Patients with advanced HCC who treated with RT plus anti-PD1 and TACE plus sorafenib were enrolled. Objective response rate (ORR), PFS, disease control rate (DCR) and OS were calculated to assess the antitumor response and the treatment-related adverse events to the safety.Results: Between January 2018 to March 2021, 37 patients underwent RT plus anti-PD1 and 41 patients underwent TACE plus sorafenib. The baseline characteristics between the two groups were comparable. The ORR and DCR were significantly higher in the RT+PD1 group than the TACE plus sorafenib group according to RECIST 1.1 (54.05% vs 12.20%, P < 0.001; 70.27% vs 46.37%, P = 0.041; respectively) and according to mRECIST (56.76% vs 31.71%, P = 0.039; 70.27% vs 46.37%, P = 0.041; respectively). RT plus anti-PD1 provided significantly better PFS (HR, 0.51; 95% CI 0.30-0.86; p=0.017) than TACE plus sorafenib. Moreover, patients with RT plus anti-PD1 had significantly higher 3-, 6-, and 9-month OS rates than those with TACE plus sorafenib(97.3% vs 92.30%, P < 0.001; 91.89% vs 68.60%, P < 0.001; 75.5% vs 60.60%, P < 0.001; respectively). The median OS was more favorable 17.4 months for the RT+PD1 group and 11.9 months for the TACE plus sorafenib group. No treatment-related death was observed. Grade 3 or more treatment-related adverse events (TRAEs) occurred significantly less in patients in the RT+PD1 group than the TACE plus sorafenib group (29.7% vs 75.6%, p < 0.001), and all TRAEs were manageable.Conclusions: In this real-world study, RT plus anti-PD1 showed significantly promising efficacy and manageable safety than TACE plus sorafenib in patients with advanced HCC. Toxicities were manageable, with no unexpected safety signals. The study provides evidence on a new therapeutic method in the treatment of advanced HCC.

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Real-world efficacy and safety of immune checkpoint inhibitors in advanced hepatocellular carcinoma: Experience of a tertiary Asian center.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.559 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 559-559

Author(s):

Kennedy Ng ◽

Lawrence Wen Jun Wong ◽

Su Pin Choo ◽

David Wai-Meng Tai ◽

Sze Huey Tan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Adverse Events ◽

Real World ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Advanced Hepatocellular Carcinoma ◽

Efficacy And Safety ◽

Advanced Hcc ◽

Increased Risk

559 Background: Immune checkpoint inhibitor (ICI) use in advanced hepatocellular carcinoma (HCC) is increasing. Real-world data on efficacy and safety however is lacking, more so when used in patients who fall out of standard clinical trial criteria. Methods: We conducted a retrospective review of all patients with advanced HCC seen at our centre who received at least one dose of an ICI between May 2015 - June 2018. Data cutoff was 31 Dec 2018. Responses were evaluated using RECIST v1.1 criteria. Results: 114 patients fulfilled inclusion criteria. Median age was 66 years and 88.6% were male. 96.5% had an ECOG PS of 0 – 1. 64.9% received an ICI within a clinical trial setting. 62.3% received monotherapy ICI. 19.6% of patients had Child-Pugh B disease on initiation of ICI, and 69.3% had an ALBI Grade of 2. 50.0% were known to have hepatitis B and 11.4% had hepatitis C. Baseline HBV VL ranged from undetectable to 8210000 IU/mL. 30.7% received prior systemic treatment, most commonly sorafenib (82.9%). Over a median follow-up duration of 5.7 months (0.03 - 42.4), ORR was 18.4%, and disease control rate (DCR) was 51.8%. Median PFS was 2.6 months (1.7 - 3.9), and median OS was 13.9 months (7.0 - 16.2). 5 patients (23.8%) had response duration of more than 18 months. 35.1% received further systemic therapy after ICI. On multivariable analyses, age ≥ 65 years, higher albumin level and lower bilirubin level were associated with increased OS. 68.0% of patients experienced adverse events (AEs) of any grade, 12.0% of these being grade 3 - 4. No grade 5 adverse events were observed. Use of antiviral therapy was associated with a lower risk of hepatic AEs (p = 0.04) whilst high baseline HBV VL was not associated with an increased risk of reactivation or hepatic AEs. Conclusions: In the real-world setting, responses and adverse event profiles to ICI use are comparable to those observed in clinical trials despite a more heterogenous population base. The expansion of indications for ICI use in advanced HCC beyond current approvals warrants greater study.

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

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001945 ◽

2021 ◽

Vol 9 (2) ◽

pp. e001945 ◽

Cited By ~ 1

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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Serum neutrophil/lymphocyte ratio as a potential predictor of treatment response for immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16156 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16156-e16156

Author(s):

Jian He ◽

Zhiqiang Mo ◽

Qicong Mai ◽

Xiaoming Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Treatment Response ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Post Treatment ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Hcc ◽

Lymphocyte Ratio ◽

Pre Treatment

e16156 Background: Neutrophil to lymphocyte ratio (NLR) has been shown to associate with tumor progression. The present study was to investigate the role of NLR on predicting the treatment response for immune checkpoint inhibitors (ICIs) therapy in patients with advanced hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed 81 patients received ICIs for advanced HCC from January 2017 to July 2019. We analyzed whether pre- and first 3 weeks post- treatment serum NLR level was associated with ICIs outcome. Results: In this study, the pre-treatment NLR level ranged from 0.64 to 14.93 among 81 patients. The cut-off level of NLR was set as the median value of 2.79. The objective response rate (ORR) in the patients with NLR＜2.79 (low NLR) was 25.0%, which was significantly better than that of patients with NLR ≥2.79 (high NLR) (7.3%, P ＝0.03). Compared to patients with high NLR, patients with low NLR exhibited significantly longer median progression-free survival (PFS) (3.7 vs 3.0 months, P ＝0.004) and median overall survival (OS) (10.3 vs 7.5 months, P ＝0.001). Multivariate analysis revealed high NLR was an independent unfavourable prognostic factor for PFS (hazard ratio [HR] = 1.857, 95% confidence interval [CI] = 1.093-3.154; P = 0.022) and OS (HR = 2.267, 95% CI = 1.221-4.207; P = 0.009). For the patients with high pre-treatment NLR level, ICIs outcome was stratified more clearly by first 3 weeks post- treatment NLR level. Conclusions: The pre- and first 3 weeks post- treatment serum NLR level could be considered as a predictive factor of treatment response for ICIs in patients with advanced HCC.

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Hepatic arterial infusion of oxaliplatin plus raltitrexed in patients with unresectable hepatocellular carcinoma (HAIROX): A phase II, single-arm, prospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4574 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4574-4574

Author(s):

Shiguang Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Adverse Events ◽

Phase Ii ◽

Objective Response ◽

Hepatic Arterial Infusion ◽

Arterial Infusion ◽

Intention To Treat ◽

Unresectable Hepatocellular Carcinoma ◽

Treat Population

4574 Background: Chemoembolisation and oral sorafenib are the recommended treatment for unresectable hepatocellular carcinoma (HCC); however, some patients respond poorly to these. Hepatic arterial infusion (HAI) chemotherapy may have potential benefit in these patients. We aimed to investigate the efficacy and safety of HAI of oxaliplatin plus raltitrexed in patients with unresectable HCC. Methods: In this phase II, single-arm clinical trial, we enrolled patients aged 18–70 years with unresectable HCC at the Fujian Cancer Hospital (China). We performed HAI with oxaliplatin (100 mg/m2 for 4 hours) and raltitrexed (3 mg/m2 for 1 hour). Treatment was repeated every 3 weeks and was discontinued either because of disease progression, unacceptable toxicity levels, or refusal of further treatment. We used Simon’s two-stage design. The primary endpoint was the objective response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Fifty-one patients were screened between January 5, 2018 and August 7, 2019. Of these, 39 patients (34 men and 5 women; median age, 53 years) were enrolled and included in the intention-to-treat population. Objective response was achieved in 18 (51.4%) of 35 patients in the per-protocol population and in 18 (46.2%) of 39 patients in the intention-to-treat population. Treatment-related grade 4 adverse events or deaths were not reported, and the observed grade 3 adverse events were elevated aspartate aminotransferase levels (5[12.8%]), elevated alanine aminotransferase levels (1 [2.6%]), leukopenia (1 [2.6%]), thrombocytopenia (1 [2.6%]), and abdominal infection (1 [2.6%]). Conclusions: HAI of oxaliplatin plus raltitrexed showed promising efficacy and acceptable toxicity levels in patients unresectable HCC, and further evaluation is warranted. Clinical trial information: ChiCTR-OOC-17014182 . [Table: see text]

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Lenvatinib plus pembrolizumab versus lenvatinib in patients with unresectable hepatocellular carcinoma: A real world study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16138 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16138-e16138

Author(s):

I-Cheng Lee ◽

Chi-Jung Wu ◽

San-Chi Chen ◽

Yee Chao ◽

Yi-Hsiang Huang

Keyword(s):

Hepatocellular Carcinoma ◽

Disease Control ◽

Real World ◽

Objective Response Rate ◽

Response Rate ◽

Objective Response ◽

Progression Free Survival ◽

Disease Control Rate ◽

Recist 1.1 ◽

Unresectable Hepatocellular Carcinoma

e16138 Background: The combination of lenvatinib (LEN) and pembrolizumab (PEMBRO) showed promising response rates and survival in a phase 1b trial for patients with unresectable hepatocellular carcinoma (HCC). Whether LEN plus PEMBRO provides better outcomes than LEN monotherapy remains unclear. The aim of this study was to compare the outcomes of LEN plus PEMBRO versus lenvatinib monotherapy in patients with unresectable HCC in the real world setting. Methods: A total of 123 patients with unresectable HCC were retrospectively enrolled, including 61 patients with LEN monotherapy and 62 patients with LEN plus PEMBRO. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) by RECIST 1.1 and modified RECIST (mRECIST) criteria. Results: One hundred and one (82.1%) patients were in BCLC stage C and 81 (65.9%) patients received LEN or LEN plus PEMBRO as first line setting. During a median follow-up period of 8.0 months, 71 (57.7%) and 31 (25.2%) of patients had disease progression and death, respectively. The median PFS was 8.4 and 4.9 months in the LEN plus PEMBRO and LEN monotherapy groups, respectively (p = 0.033). The median OS was not reached in the LEN-PEM group and was 17.2 months in the LEN monotherapy group (p = 0.064). Patients with LEN plus PEMBRO had higher objective response rate (ORR: 34.4% vs 23.7% by RECIST 1.1, p = 0.277; 57.4% vs 32.2% by mRECIST, p = 0.010) and higher disease control rate (83.6% vs 62.7% by RECIST 1.1, p = 0.017; 85.2% vs 62.7% by mRECIST, p = 0.009). In subgroup patients with BCLC stage C, LEN plus PEMBRO provided significantly longer PFS (9.1 vs 4.8 months, p = 0.008), higher ORR (60% vs 33.3%, p = 0.015) and higher DCR (88% vs 60.4%, p = 0.004) by mRECIST criteria. Conclusions: LEN plus PEMBRO provides significantly better ORR, DCR and PFS then LEN monotherapy for patients with unresectable HCC.

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Correlation of patient characteristics with clinical outcomes of camrelizumab combined with apatinib for unresectable hepatocellular carcinma (uHCC): An observational retrospective analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16120 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16120-e16120

Author(s):

Gang Liu ◽

Liansheng Gong ◽

Wenxuan Zhou ◽

Xiaoli Li ◽

Fei Wang ◽

...

Keyword(s):

Adverse Events ◽

Real World ◽

Subgroup Analysis ◽

Therapeutic Efficacy ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Therapeutic Effects ◽

First Line ◽

Real World Data ◽

Baseline Serum

e16120 Background: There is limited data on clinical parameters to evaluate the therapeutic effects on immune checkpoint inhibitors (ICIs) combined with anti-angiogenic agent for uHCC. Here, we assessed efficacy and safety of camrelizumab combined with apatinib for uHCC from real-world data, and performed the retrospective subgroup analysis to investigate the potential factors related to therapy response and patients survival as well. Methods: We evaluated clinical data and outcome of 26 uHCC patients who received camrelizumab 200 mg intravenously every 2 weeks combined with apatinib 250 mg qd between May 2019 and Jul 2020. Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS) were evaluated using independent central review mRECIST and RECIST 1.1. Treatment related adverse events (TRAEs) and immune-related adverse events (irAEs) were evaluated. Results: The patients’ characteristics of our cohort are summarized in Table. Overall, our study shows that ORR was 57.7% (mRECIST), DCR was 84.62% (mRECIST), median PFS (mPFS) and OS (mOS) were 11 months and 18.2 months, respectively. For subgroup analysis, patients with first-line therapy (n=22) had dramatically better mPFS than non-first-line (15.0 vs. 4 months; p=0.01). Patients with baseline serum alpha-foetoprotein (AFP) > 400 ng/ml shows better therapeutic efficacy ( p<0.001). The patients with decreased AFP level after treatment had significantly longer mPFS (15.0 vs. 4 months; p<0.001) and mOS (NR vs. 5.7 months; p<0.001) than others. Overall, 14 (53.85%) patients had grade≥3 TRAEs, only 3 (11.54%) patients had grade≥2 irAEs. Conclusions: The first up-to-date real-world evidence indicates that both the baseline and post-treatment AFP level might be independent prognostic factors to evaluate the therapeutic efficacy and clinical outcome on the combination therapy of camrelizumab and apatinib. While larger sample sizes and longer follow-up study are needed to verify reliability of statistical results.[Table: see text]

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The Real-World Data in Japanese Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib from a Nationwide Multicenter Study

Cancers ◽

10.3390/cancers13112608 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2608

Author(s):

Kaoru Tsuchiya ◽

Masayuki Kurosaki ◽

Azusa Sakamoto ◽

Hiroyuki Marusawa ◽

Yuji Kojima ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Bone Metastasis ◽

Multicenter Study ◽

Real World ◽

Vascular Invasion ◽

Response Rate ◽

Objective Response ◽

High Response Rate ◽

Real World Data ◽

Unresectable Hepatocellular Carcinoma

Background: Lenvatinib (LEN) has been approved for patients with unresectable hepatocellular carcinoma (u-HCC) since March 2018 in Japan. We performed a retrospective nationwide multicenter study to clarify the clinical characteristics of LEN in real-world practice. Methods: A total of 343 u-HCC patients who received LEN from March 2018 to May 2020 at 23 sites in Japan were registered. Results: During the median observation period of 10.5 months, 143 patients died. In Child-Pugh A (n = 276) and Child-Pugh B (n = 67) patients, the median overall survival (OS) was 21.0 and 9.0 months. The median progression-free survival (PFS) was 8.8 months in Child-Pugh A patients. The objective response rate (ORR) and disease control rate (DCR) according to modified response evaluation criteria in solid tumors (RECIST criteria) were 42.1% and 82.1%. The independent pretreatment factors associated with mortality in all patients were AFP ≥ 400 ng/mL (hazard ratio (HR) 2.00, 95% confidential interval (95% CI) 1.08–2.09, p < 0.0001), modified albumin-bilirubin (ALBI) grade 2b or 3 (HR 1.56, 95% CI 1.09–2.17, p = 0.012), major vascular invasion (HR 1.91, 95% CI 1.26–2.89, p = 0.0022), PS > 0 (HR 1.50, 95% CI 1.09–2.08, p = 0.014), and MTT (molecular targeted therapy) experience (HR 2.22, 95% CI 1.56–3.13, p = 0.00038). In the MTT naïve patients with ALBI grade 1 or modified ALBI 2a and BCLC stage B (n = 68), median OS and PFS were 25.3 and 12.3 months. Liver-related adverse events during LEN were the only significant adverse event associated with OS (HR 2.74, 95% CI 1.93–3.88, p < 0.0001). Among the Child-Pugh A patients with extrahepatic metastasis and no major vascular invasion, median PFS in the patients with bone metastasis was significantly shorter than those with lung or adrenal grand metastasis (6.3 vs. 12.5 months, p = 0.0025). Conclusion: LEN showed a high response rate in real-world practice. Pretreatment factors, including ALBI score, AFP, and major vascular invasion are important in making a treatment strategy for patients with u-HCC. The patients with bone metastasis would be candidates for new therapeutic approaches.

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Immunotherapy for hepatocellular carcinoma: recent advances and future perspectives

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835919862692 ◽

2019 ◽

Vol 11 ◽

pp. 175883591986269 ◽

Cited By ~ 23

Author(s):

Weiqi Xu ◽

Ken Liu ◽

Minjiang Chen ◽

Jin-Yu Sun ◽

Geoffrey W McCaughan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Death ◽

Programmed Cell Death ◽

Phase I ◽

Checkpoint Inhibitors ◽

Killer Cell ◽

Objective Response ◽

Phase Iii ◽

Future Research ◽

Advanced Hcc

The introduction of immunotherapies has been a major development in the treatment of many advanced cancers, including hepatocellular carcinoma (HCC). We are entering a new era of systemic therapy for advanced HCC associated with an explosion of clinical trial activity. Data from phase I/II studies of checkpoint inhibitors in advanced HCC have been promising, with durable objective response rates of approximately 20% seen (in both first- and second-line settings) and acceptable safety profiles (including immune-mediated hepatitis). Phase III studies evaluating anti-programmed cell death protein 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1) antibodies compared with sorafenib are already underway. The potential synergistic effects of anti-PD-1/anti-PD-L1 when used in combination with agents against other checkpoint molecules, systemic therapies, as well as conventional surgical and locoregional therapies are also being explored in upcoming clinical trials. Aside from this, other strategies to harness the immune system, including chimeric antigen receptor-engineered T cells, natural killer cell therapies, and peptide vaccines directed against HCC antigens have entered phase I/II studies. Current limitations of immunotherapies and areas of future research include the accurate assessment and prediction of tumor response, overcoming the immunosuppressive effects of a hypoxic microenvironment, and the management of immune-related hepatitis in patients who already have limited liver reserve.

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