bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunotherapy versus tyrosine kinase inhibitors in advanced hepatocellular carcinoma in first-line setting: A systematic review and meta-analysis of randomized controlled trials.
Authors: Marin Comini Ana Carolina Carolina , Sousa Isadora Martins de , Reis Pedro Cotta Abrahão , Carvalho Bruno Murad , Camandaroba Marcos Pedro Guedes
Published: June 2023

e16132

Background: Hepatocellular carcinoma has a high mortality rate, with an overall 5-year survival of less than 20%. Whether the use of immune checkpoint inhibitors (ICI) is superior to tyrosine kinase inhibitors (TKI) as a first-line therapy remains unclear. Methods: We performed a systematic review and meta-analyses of randomized clinical trials (RCTs) to compare ICI, in monotherapy or combined with TKI or anti-VEGF monoclonal antibody in naïve treatment. We searched Embase, PubMed and Cochrane Library databases from inception to November 2022. The outcomes evaluated were Overall Survival (OS), Progression Free-Survival (PFS), Overall Response Rate (ORR) and Treatment Related Adverse Events (TRAE). Using a random-effects model, statistical analysis was performed with RevMan 5.4 version for proportions and risk ratios for binary outcomes from comparative studies. Results: We included 10 RCTs comprising 6097 patients in the final analysis, 2554 in ICI monotherapy, 1096 in ICI with anti-VEGF and 2447 in ICI with TKI. The use of ICI, alone or in combination therapy, was associated with a better OS (HR 0.77; 95% CI 0.69–0.85; p< 0.00001; I²=46%) and PFS (HR 0.77; 95% CI 0.64-0.92, p=0.005; I²= 85%). In the ICI monotherapy subgroup, there was a statistical difference to TKI in OS (HR 0.82; 95% CI 0.75-0.91; p=0.0001; I² = 0%). Although there was a higher ORR in all ICI groups (RR 2.56; 95% CI 1.89-3.46; p<0.00001, I²=68%), TRAE Grades 3-4 (RR 0.85; 95% CI 0.61-1.18; p=0.33; I²=96%) presented no difference when compared with TKI. Conclusions: Our findings suggest that the use of ICI, alone or in combination with TKI or anti-VEGF, is a superior option for first-line therapy for advanced hepatocellular carcinoma, improving OS, PFS, and ORR without increasing treatment toxicity. These results are important for guiding clinical decision-making and further research in this field.
Gaps in care planning and delivery for patients with liver cancer: Baseline assessment for implementation of 4R Oncology model.
Authors: Therapondos George , Trosman Julia R. , Du Lingling , Mizrahi Jonathan , Sandow Tyler Allan , Cohen Ari , Gimenez Juan , Palmer Carol , Medina Amanda , O'Brien Michelle , Tan Amie , Weldon Christine B.
Published: June 2023

e16136

Background: Liver cancer is a complex disease, requiring detailed care planning, patient engagement and delivery of comprehensive care, including supportive and health maintenance care. The 4R Oncology Model for patient facing care planning, patient self-management and team based delivery of complex care has the potential to address these needs. 4R (Right Info/Care/Patient/Time) significantly improves patient self-management and optimizes delivery of supportive and health maintenance care in breast and lung cancer (Trosman JCOOP 2021; Liu JCOOP 2022). The impact of 4R in liver cancer has not been examined. Ochsner Health’s multi-disciplinary live cancer team is implementing and evaluating 4R. Here we describe the baseline assessment of provider practices and patient experience of care planning and delivery of supportive and health maintenance care. Methods: Surveys of providers and patients on current care planning and delivery in liver cancer were conducted Oct 2022 – Jan 2023. We used 3 metrics of care planning and 3 metrics of care delivery (Table). Results: Survey response rates: providers 55% (33/60), patients 43% (27/63). Providers included physicians, advance practitioners, nurses and navigators from Hepatology, Transplant, Interventional Radiology and Medical Oncology. Patients were 56% female, 63% white, 37% black, 56% < 30k income. In care planning, patient experience was reported at a similar rate as provider practices for informed on goal of care, but significantly higher than providers for informed on next steps in care and receiving a detailed care plan (Table). In care delivery, patient experience and provider referral practices for social and supportive care were similarly low. Rates of patients’ receiving primary care and substance abuse assistance were significantly higher than respective rates of provider referrals. Among providers, 73% give patients a verbal care plan and 27% a hand written plan. The current process to create care plans is satisfactory to 54% of providers. Conclusions: We found substantial gaps in care planning and referrals to supportive and health maintenance care. Higher rates of patients reporting receipt of care planning and services suggest that many patients may resort to their own devices in these aspects of care. Ochsner Health aims to address these gaps by implementing the 4R Oncology model in liver cancer and will share results when available. [Table: see text]
Identification of prognostic tumor microenvironment in patients with advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy in combination with lenvatinib and PD-1 inhibitors.
Authors: Guo Wenbo , Chen Song , Zhao Lihua , Wu Zhiqiang , Cai Hongjie , Wang Fan , Wu Lijia
Published: June 2023

e16141

Background: The triple combination therapy of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has shown promising outcomes in patients with advanced hepatocellular carcinoma (HCC) as a first-line treatment. However, the tumor microenvironment (TME) characteristics of the beneficiary population are still unclear. This study aimed to generally explore the TME characteristics of patients receiving the triple combination therapy by baseline tumor tissues. Methods: A total of 44 patients were prospectively enrolled in this single-center study. Ultimately, 38 biopsy-proven patients were treated with HAIC with oxaliplatin, leucovorin, 5-fluorouracil (FOLFOX), lenvatinib, and PD-1 inhibitors. According to the tumor response elevated by the modified RECIST (mRECIST), the 38 patients were divided into the response group with complete response (CR) and partial response (PR) and the non-response group with stable disease (SD) and progression disease (PD). Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Meanwhile, the cancer gene-targeted next-generation sequencing (NGS) and RNA sequencing (RNA-seq) were performed to describe the differences between the two groups of biopsy samples to identify the prognostic TME characteristics. Results: Among the 38 patients, 22 patients were distributed to the response group, and the remaining 16 patients were included in the non-response group. The response group and the non-response group were significantly different in median OS (not-reached vs. 8.6 months; HR, 0.22, 95% CI 0.08-0.58; p< 0.001) and median PFS (15.3 months vs. 2.0 months; HR, 0.31, 95% CI 0.13-0.75; p= 0.001). The most common AEs were AST elevation (84.2%), stomachache (76.3%), nausea (63.2%), and hypertension (52.6%). Grade 3/4 AEs occurred 14 times among 12 patients, and no treated-related deaths were observed. For the cancer gene-targeted NGS, no specific enrichment for gene mutations was identified to be related to prognosis. As for the TME analysis by RNA-seq, the response group was characterized by a more beneficial infiltration of immune cell subsets, and high tumor-infiltrating T lymphocytes were associated with a higher response rate, longer PFS and OS. Conclusions: In this study, HAIC plus lenvatinib and PD-1 inhibitor as first-line therapy displayed promising efficacy and manageable side effects in patients with advanced HCC. The differences in the initial TME of patients, especially in tumor-infiltrating T lymphocytes, may be potential biomarkers for predicting response and prognosis. This finding provides clues to search for biomarkers for the triple combination therapy of HAIC combined with lenvatinib and PD-1 inhibitors in advanced HCC.
Efficacy and safety of radiotherapy combined with regorafenib for advanced hepatocellular carcinoma: A real-world study from a single center.
Authors: Xin Lingxia , Wang Liming , Zhai Yirui , Wang Shulian , Tang Yuan , Liu Yueping , Song Yongwen , Fang Hui , Li Ning , Qi Shunan , Lu Ningning , Li Ye-Xiong , Chen Bo
Published: June 2023

e16142

Background: This study aimed to assess the efficacy and safety of radiotherapy (RT) combined with regorafenib as a second or further-line treatment for advanced hepatocellular carcinoma (HCC). Methods: Patients diagnosed with advanced HCC who had received RT combined with concurrent or sequential regorafenib treatment or regorafenib plus anti-PD-1 or anti-PD-L1 immune checkpoint inhibitors (ICIs) in our hospital from April 2018 to August 2022 were reviewed. Progression-free survival (PFS) was the primary endpoint. Overall survival (OS), objective response rate (ORR), disease control rate (DCR) and toxicity were the secondary endpoints. Results: Fifty-four patients were included with a median age of 56 (38-73). Forty-six patients (85.2%) were in Barcelona Clinic Liver Cancer (BCLC) stage C. Thirty-seven patients (68.5%) had portal vein tumor thrombosis and 15 (27.8%) had extrahepatic metastasis. All patients received intensity modulated radiation therapy, while 26 patients were concurrently treated with regorafenib and 28 patients were sequentially treated with regorafenib. The median dose of radiotherapy was 57.2Gy (30-69.8Gy). Anti-PD-1/anti-PD-L1 agents were applied to 31 patients at the use of regorafenib. The median PFS was 11.3 months. The 3-year PFS and OS were 23.8% and 51.9%, respectively. Treatment response after RT was shown. For tumor in in-field of RT, ORR was 75.9% and 92.6% according to RECIST and mRECIST criteria, respectively. No progression was found in in-field of RT. Out-field recurrence in liver and distance metastasis was the main failure pattern. For all lesions, the ORR was 40.7% and DCR was 55.6%, respectively. There was no significant difference of PFS and OS between patients with and without ICIs ( p > 0.05). Univariate analysis showed that alpha-fetoprotein tumor marker level ≥ 1000 ng/ml ( p = 0.049), Albumin-Bilirubin grade ≥ 2 ( p = 0.012) and multiple intrahepatic tumors ( p = 0.031) were the risk factors of lower PFS. Patients were well tolerated to the treatments. The most common grade 3 toxicities were hand-foot syndrome (11.1%), fatigue (3.7%) and hypertension (1.9%). Classical or non-classical radiation-induced liver disease was not noted. Conclusions: Radiotherapy concurrently or sequentially with regorafinib treatment is an effective, well tolerated, and promising regimen in advanced HCC patients. [Table: see text]
A real-world study of TACE combined with regorafenib as a second-line treatment for advanced hepatocellular carcinoma.
Authors: Liu Shaoxing , Gao Song , Guo Jianhai , Kou Fuxin , Zhang Xin , Liu Baojiang , Feng Aiwei , Wang Xiaodong , Chen Hui , Zhu Xu
Published: June 2023

e16144

Background: Regorafenib is a guideline-recommended second-line systemic drug, and its combination with transarterial chemoembolization (TACE) for the treatment of advanced liver cancer after first-line therapy has been gradually recognized by clinicians. We investigated the efficacy and safety of TACE combined with regorafenib with or without anti-PD-1 immunotherapy as a second line choice for advanced hepatocellular carcinoma (HCC). Methods: In this retrospective study, we retrieved patients with advanced liver cancer who had failed first-line therapy in our center from January 2019 to December 2021, and screened out patients who received TACE combined with regorafenib as second-line therapy. The data of objective response rate (ORR), progression-free survival (PFS) and adverse reactions (ARs) of treatment in these patients were analyzed and summarized. Subgroup analysis of patients with and without PD-1 inhibitors was also performed. Results: A total of 43 eligible patients were screened and treated with TACE in combination with regorafenib in second-line therapy, including 29 patients treated with PD-1 inhibitors. In all patients, one patient had complete response (CR) and 11 patients had partial response (PR), with ORR of 27.91% (12/43) and 24 patients had stable disease (SD), with disease control rate (DCR) of 83.72% (36/43). The median PFS was 10.0 months for all patients in survival follow-up, with PFS rates of 77.65% and 37.17% at 6 and 12 months follow-ups, respectively. Overall survival (OS) rates were 90.49%, 67.03%, and 58.65% at 12, 18, and 24 months, respectively. In subgroup analysis, there was no statistical difference in median PFS between the groups with or without PD-1 inhibitors (11.0 months vs 8.0 months, p=0.229), but there was a trend toward survival benefit in the combined group (hazard ratio/HR 0.62). The incidence of treatment-related ARs in all treated patients was 81.40% (35/43), all grade 1-2. Among ARs, hand-foot syndrome (27.91%), loss of appetite (20.93%), and elevated transaminases (16.28%) were predominant. Conclusions: This study verified the efficacy and safety of TACE combined with regorafenib as second-line therapy for the treatment of advanced HCC after failure of first-line therapy, and the results need to be further justified in future prospective studies with larger sample sizes. [Table: see text]
Hepatic arterial infusion chemotherapy (HAIC) combined with tislelizumab and lenvatinib for advanced hepatocellular carcinoma (aHCC) with Vp3-4 portal vein tumor thrombosis (PVTT): A single-arm, phase II study.
Authors: Xu Yongkang , Fu Shumin , Mao Ye , Huang Shenglan , Li Dan , Wu Jianbing
Published: June 2023

e16145

Background: aHCC patients (pts) with Vp3-4 PVTT have a poor prognosis. HAIC combined with immune checkpoint inhibitors and targeted therapies has shown local control and survival benefits in aHCC. However, the optimal combination in aHCC pts with Vp3-4 PVTT remains unclear. Here, we reported the preliminary efficacy and safety of HAIC combined with tislelizumab and lenvatinib in this population. Methods: In this ongoing, single-site, prospective, single-arm, phase II study, eligible pts were aged ≥18 years, histologically confirmed aHCC, ECOG PS ≤1, Child-Pugh A/B, and had at least 1 measurable lesion per RECIST 1.1. Pts received HAIC with modified FOLFOX (oxaliplatin, 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1; and 5-fluorouracil infusion 2400 mg/m2 for 46 h), combined with lenvatinib (8 or 12 mg QD for body weight <60 or ≥60 kg) and tislelizumab (200mg Q3W). HAIC was conducted repeatedly on demand. The primary endpoint was the objective response rate (ORR) per RECIST 1.1. Secondary endpoints included the ORR per mRECIST, disease control rate (DCR), surgical conversion rate, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Results: From June 2021 to January 2023, 27 aHCC pts with Vp3-4 PVTT were enrolled; of these, 22 pts were valuable for efficacy and safety analyses. The 22 pts were characterized with a median age of 52.5 years (range 33-72), 40.9% ECOG PS 0, 90.9%Child-Pugh A, and 45.5% extrahepatic metastasis. Till data cut-off (January 20, 2023), median follow-up was 11.3 months (95% CI, 6.0-13.1), 17 pts were alive and 14 pts remained on treatment. The ORR was 45.5% (95% CI, 25.1%-67.3%) with all partial responses per RECIST 1.1. Notably, 17 of 22 pts (77.3%; 95% CI, 54.2%-91.3%) achieved objective response as per mRECIST, with 6 (27.3%) complete responses and 11 (50%) partial responses. The DCR was 90.9% (95% CI, 69.4%-98.4%) either by RECIST 1.1 or mRECIST. Surgical conversion was achieved in 22.7% (5/22; 95% CI, 8.7%-45.8%) pts. Median PFS was not reached, with a 6- and 12-month PFS rate of 50% and 27.3%. OS data was not mature by the cut-off date. TRAEs were reported in 18 of 22 pts (81.8%). Most common TRAEs of any grade were hypertension (11/22, 50%), neutropenia (10/22, 45.5%), and aspartate aminotransferase (AST) increased (7/22, 31.8%). Grades ≥3 TRAEs occurred in 6 pts (27.3%), including 3 neutropenia (13.6%), 2 abdominal pain (9.1%), and 1 AST increased (4.6%). Conclusions: HAIC combined with tislelizumab and lenvatinib showed encouraging clinical activity and acceptable toxicity in aHCC pts with Vp3-4 PVTT, suggesting that this combination could be considered in this population. Study enrollment is ongoing, more mature data will be presented later. Clinical trial information: ChiCTR2200064384 .
Comparative efficacy and safety of anti-PD-1/L1 antibody plus anti-VEGF antibody and anti-PD-1/L1 antibody plus VEGFR-targeted tyrosine kinase inhibitor as first-line therapy for unresectable hepatocellular carcinoma (uHCC): A systematic review and network meta-analysis.
Authors: Jieer Ying , Zhuo Yiwen , Li Jingjing , Lu Beibei , Zheng Yuxi
Published: June 2023

e16148

Background: Anti-PD-1/L1 antibody combined with anti-VEGF antibody and anti-PD-1/L1 antibody combined with VEGFR-targeted tyrosine kinase inhibitor are both effective first-line therapies for uHCC in clinical practice widely. However, direct comparisons across the two regimens are not available. We conducted a network meta-analysis of them in terms of overall survival (OS), progression free survival (PFS), objective response rate (ORR) and incidence of treatment-related adverse events (TRAEs). Methods: After a literature research performed in PubMed, MEDLINE, Embase, the Cochrane library and several major scientific societies from January 1 2007 to November 6 2022, 3,279 records were obtained. 6 phase III trials has been identified for the final analysis: REFLECT, IMbrave150, ORIENT-32, COSMIC-312, Qin 2022 and LEAP-002. The experiments were broadly classified into three groups: anti-PD-1/L1 antibody + anti-VEGF antibody (IMbrave150 and ORIENT-32), anti-PD-1/L1 antibody + VEGFR-targeted tyrosine kinase inhibitor (COSMIC-312, Qin 2022 and LEAP-002) and intermediate reference group (lenvatinib vs sorafenib, REFLECT). We derived hazard ratios (HR) with 95% confidence intervals (95%CI) for OS and PFS, odds ratio (OR) for ORR and relative risks (RR) for all grade and grade ≥3 TRAEs. With fixed effect models to estimate the indirect pooled HRs, ORs, RRs and 95%CI, a frequentist network meta-analysis was conducted using sorafenib as intermediate reference. Results: 4,012 patients were included in the analysis overall, among them, 1815 patients were treated with anti-PD-1/L1 antibody+VEGF-antibody (A+A), 1,099 patients were treated with anti-PD-1/L1 antibody+VEGFR-TKI (A+T), 877 patients were treated with lenvatinib (LEN) and 1,320 patients were treated with sorafenib (SOR). With a p-score of 98%, the combination of A+A provided the greatest reduction in the risk of death, was not significantly different from A+T (HR=0.84, 95%CI: 0.66-1.06). Besides, A+T were associated with the greatest effect in prolonging PFS and improving ORR with 91% for p-score, but there are no statistical differences with A+A (HR=1.06, 95%CI: 0.87-1.30, OR=0.82, 95%CI: 0.47-1.46). Considering the risk of TRAEs, A+A were significantly safer than A+T (RR=0.91, 95%CI: 0.84-0.98) in all grade of TRAEs and ≥3 grade (RR=0.91, 95%CI: 0.84-0.98). Conclusions: The combination of anti-PD-1/L1 antibody and anti-VEGF antibodies has the greatest probability of delivering the longest OS, while anti-PD-1/L1 antibody plus VEGFR-targeted tyrosine kinase inhibitor is correlated with larger PFS benefit at the cost of a lower safety rate.
Efficacy and safety of regorafenib and PD-1 combined with cryoablation in the treatment of advanced hepatocellular carcinoma after second-line targeted therapy.
Authors: Chen Yan , Kong Huifang , Wang Sihao , Zhang Wei , Chang Xiujuan , Huang Jiagan , Dong Zheng , Gao Xudong , Yang Bin , Zhang Huixin , Zhang Bailong , Yang Yongping , Zeng Zhen
Published: June 2023

e16151

Background: Targeted therapy is the most effective therapeutic approach for middle and late-stage hepatocellular carcinoma (HCC). Regorafenib or PD-1 as a second-line treatment of patients with advanced HCC has achieved good results. Argon-helium cryoablation is one commonly used method for local ablation of liver cancer. Whether systemic therapy combined with local therapy can benefit patients with advanced liver cancer is a hot topic. This study is aimed to investigate the efficacy and safety of regorafenib and PD-1 combined with cryoablation in the treatment of patients with advanced HCC after the failure of second-line targeted treatment. Methods: In this retrospective study, unresectable HCC patients received regorafenib and PD-1combined with cryoablation after the failure of second-line targeted treatment from January 2019 to December 2021 were enrolled. Depending on whether combining local therapy, patients were grouped as RP (regorafenib and PD-1), or RPC groups (regorafenib and PD-1 combined with cryoablation). Objective response rate (ORR), disease control regorafenib rate (DCR), progression free survival (PFS), and safety were recorded. The PFS was defined as the time from the first dose of RP, or from the time of using RPC until disease progression or death. Results: A total of 50 patients were reviewed, including 21 patients in RP group and 29 patients in RCP group. One patient was classified as Barcelona Clinic Liver Cancer (BCLC) stage B and 20 patients were at BCLC stage C in RP group, while one patient was at BCLC stage B and 28 patients were at BCLC stage C in RPC group. The ORR and DCR were 4.8% and 23.8% in PR group respectively, and 31.0% and 69.0% in RPC group respectively. The 6-month PFS rate of RP group and RPC group was 14.3% and 53.6% respectively. Thirteen (61.9%) and eighteen (62.1%) patients experienced adverse events (AEs) in two groups respectively. Two (9.5%) and three (10.7%) patients experienced grade 3 AEs that occurred in RP group and RPC group respectively. The most frequency AE was hand-foot-skin reaction in both groups (58.0% and 50.0%, respectively). No patient discontinued regorafenib and PD-1 due to AE in these two groups. Conclusions: Regorafenib and PD-1 combined with cryoablation showed potential anti-tumor effect and tolerance on unresectable HCC after the failure of second-line targeted treatment. [Table: see text]
Landscape of FGFR2/3 alterations in hepatobiliary malignancies.
Authors: Liu Hongyan , Liu Huanhuan , Qin Jiayue , Cao Shanbo
Published: June 2023

e16152

Background: Genomic aberrations (GAs) in FGFRs are involved in the pathogenesis of Hepatobiliary Malignancies, and clinical trials have shown efficacy of FGFR inhibitors in treating hepatobiliary malignancies patients with FGFR GAs. However, the molecular profile of FGFR2/3 in hepatobiliary malignancies is still lacking. Here, we focused on mutational landscape of FGFR2/3 GAs in hepatobiliary malignancies. Methods: We prospectively sequenced 876 tumors and matched blood DNA from Chinese and TCGA patients with hepatobiliary malignancies using next-generation sequencing techniques. Comprehensive molecular characterization was analyzed. Results: 13.2% (116/876) hepatobiliary malignancies carried FGFR2/3 GAs, including somatic mutation (56, 6.4%), CNV (41, 4.7%), and fusion (23, 2.62%). In FGFR2/3 mutation cohorts, the five most frequently somatic mutated genes were TP53 (46%), NCOR2 (26%), LRP1B (18%), KMT2C (17%), and FAT1 (16%), except for FGFR2 and FGFR3 gene. For FGFR2/3 wildtype cohorts, the five most frequently mutated genes were TP53 (46%), NCOR2 (13%), CTNNB1 (12%), LRP1B (12%), and ARID1A (10%). 77 mutated genes were significant difference between FGFR2/3 mutation and FGFR2/3 wildtype cohorts, such as NCOR2, KMT2C, FAT1, ROS1 and KMT2B, excluding the FGFR2 and FGFR3 gene. In addition, patients with FGFR2/3 GAs harbored a significantly higher TMB than those in patients without FGFR2/3 GAs (12.6 vs 9.0, p=0.003). There was no significant difference in genomic instability between the FGFR3 mutant group and the wild group (p>0.05), including ploidy, wGII, and ITH. Conclusions: FGFR2/3 GAs are frequently altered in hepatobiliary malignancies. Comprehensive genomic profiling of FGFR2/3 GAs highlights the clinical and therapeutic implication. There were characterized the genomic differences and similarities, stratified by the FGFR2/3 status, which may reflect the hepatobiliary malignancies patients with FGFR2/3 GAs harbored specific molecular mechanism.
Efficacy and safety in unresectable hepatocellular carcinoma with VP4 tumor embolus using sinilimab plus bevacizumab: A retrospective analysis of real-world evidence.
Authors: Cheng Jiamin , Chen Bowen , Zhang Xinfeng , Su Guodong , Peng Caiyun , Lei Jin , Yu Lingxiang , Li Yinyin , Lu Yinying
Published: June 2023

e16156

Background: Recently, sinilimab plus bevacizumab has shown promising effects on unresectable hepatocellular carcinoma (uHCC) in ORIENT-32. However, its efficacy and safety in uHCC patients with VP4 cancer embolus remained unclear. Methods: In this retrospective study, uHCC patients with VP4 tumor embolus who received first-line sinilimab plus bevacizumab were consecutively enrolled. We also included similar patients who were treated with first-line sorafenib as comparison. Main efficacy endpoint was overall survival (OS), following progression free survival (PFS), objective response rate (ORR) and disease control rate (DCR) to be secondary endpoints, evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: Total 43 eligible patients were enrolled, with 15 in sinilimab plus bevacizumab arm (arm 1) and the other 28 in sorafenib arm (arm 2). No statistical differences were found in etiology, liver function and performance status. At data cut-off at February 2023, median PFS in arm 1 and arm 2 were 3.7 (95%CI: 1.2-6.2) and 3.8 (95%CI:3.1-4.5) months, following ORR and DCR were 6.7% & 46.7% and 7.1% & 35.7%. OS in arm 1 was not matured and in arm 2 was 16.1 (11.1-21.1). Not any difference was detected among all efficacy endpoints. AEs happened among almost all patients. But nobody died of AEs. Conclusions: Efficacy and safety of sinilimab plus bevacizumab in uHCC patients with VP4 tumor embolus was similar with sorafenib, which needs to be further confirmed. [Table: see text]
Combined immune checkpoint inhibition with durvalumab and tremelimumab with and without radiofrequency ablation in patients with advanced biliary tract carcinoma.
Authors: Monge B. M. Cecilia , Coffman Kelley Lauren , Hrones Donna M. , Steinberg Seth M. , Redd Bernadette , Wood Bradford , Xie Changqing , Greten Tim F.
Published: June 2023

e16158

Background: The prognosis of advanced bile tract cancer (BTC) is unfavorable with a 5-year overall survival (OS) rate of less than 10%. Durvalumab has been approved in the first line setting in combination with chemotherapy (gemcitabine with cisplatin) for advanced BTC. Monotherapy with immune checkpoint inhibitors (ICI) in BTC in the second line is suboptimal with ORR reported in the 5-15% range. The purpose of this study was to explore the efficacy of an anti-PD-L1 (durvalumab) agent in combination with an anti-CTLA4 (tremelimumab) agent with and without radio frequency ablations (RFA) in advanced BTC. Methods: Eligible patients with advanced BTC who had received or refused at least one prior line of systemic therapy were treated with tremelimumab 75 mg intravenously (IV) and durvalumab 1500 mg (IV) for 4 combined doses followed by monthly durvalumab 1500 mg IV alone until progression of disease or unacceptable toxicity. Objective response was assessed through CT or MRI by Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) every 8 weeks. Adverse events (AEs) were recorded and managed. The primary endpoint was 6-month progression free survival (PFS). All patients underwent a pretreatment and on treatment biopsy. Results: 22 patients with advanced BTC were enrolled in this study; 10 patients were treated with durvalumab and tremelimumab (Durva/ Treme -Arm A) and 12 patients were treated with the combination of durvalumab and tremelimumab and an ablative procedure (Durva/ Treme/ RFA -Arm B). A total of 18 patients were evaluable (10 in Arm A and 8 in Arm B). The best clinical response in Arm A were as follows: PR (n=8), SD (n=1), PD (n=1) and in Arm B: SD (n=3), PD (n=5). The median progression free survival (PFS) in the Durva/ Treme Arm A was 3.3 months (95% CI: 1.9-3.9) and Durva/ Treme/ RFA Arm was 2 months (95% CI: 1.3-2.5)). The median overall survival (OS) in the Durva/ Treme Arm A was 6.1 months (95% CI: 3.5-7.4) and Durva/ Treme/ RFA Arm was 5.7 months (95% CI: 2.9-7.6). The most common study hematologic related Grade 3-4 adverse events (AEs) were lymphopenia (n=6) and anemia (n=3) and the most common non hematologic AEs included increased AST (n=9), increased alk phos (n=7) and increased total bilirubin (n=6). Conclusions: Combined ICI with Durva/ Treme with and without RFA is well tolerated; Durva/ Treme alone showed promising activity in this small early-stage study, with an ORR of 80%, in patients with advanced BTC. Clinical trial information: NCT02821754 .
Efficacy and safety of regorafenib + PD-1 inhibitor combined with local therapy as second-line treatment in patients with advanced hepatocellular carcinoma: A multicenter retrospective real-world study.
Authors: Fu Xiaobo , Mu Maoyuan , Qi Han , Jiang Weiwei , Chen Zixiong , Gao Fei
Published: June 2023

e16159

Background: Regorafenib and PD-1 inhibitor both are recommended as the standard second-line treatment for advanced hepatocellular carcinoma (HCC) in currently authorized guidelines. Local interventional therapies showed significant benefits in the treatment of HCC. We aimed to evaluate to investigate the efficacy and safety of regorafenib + PD-1 inhibitor combined with intervention therapy as the second-line treatment option for advanced HCC. Methods: From October 2019 to February 2022, 31 patients with advanced HCC treated with regorafenib+PD-1 were retrospectively included. All patients were divided into two groups: group A (n = 17, patients received regorafenib +PD-1 combined with local therapy), and group B (n = 14, patients received regorafenib+PD-1). The inclusion criteria are as follows: the first-line treatment was sorafenib or lenvatinib; advanced HCC (BCLC-C); ECOG score was 0-1; Child-Pugh score was 5-7; at least one measurable lesion; expected survival time ≥ 3 months. The treatment efficacy was evaluated by modified-RECIST. Objective response rate (ORR) and disease control rate (DCR) were evaluated in two groups. Major complications referred to those that result in death or serious adverse effects including sepsis, uncontrollable bleeding, and acute renal failure; others were considered minor complications. Results: The median follow-up time was 12.9 months. The median PFS was 8.3 months vs. 7.5 months (p = 0.814). The median TTP (Time to Progression) time was 8.3 months vs. 7.5 months (p = 0.973). In group A, eleven patients received TACE, 2 received thermal ablation, and 4 received HAIC. In group A: four patients reached PR (Partial response), and 7 patients stayed SD (Stable disease), while six patients suffered tumor progression (PD, Progression disease); In group B, only one patient reached PR, and 7 patients stayed SD, 6 patients suffered tumor progression. The ORR was 23.5% (group A) vs. 7.1% (group B), respectively. The DCR was 64.7% (group A) vs 57.1% (group B), respectively. The daily dose of Regorafenib was 80mg (58.8%), 120mg (29.4%), and 160mg (11.8%), respectively in group A. The daily dose of Regorafenib was 80mg (57.1%), 120mg (28.5%), and 160mg (14.3%), respectively in group B. The dose for the PD-1 inhibitor was 200mg (every three weeks). Adverse events of systemic drugs in group A and group B were 58.8% (10/17), and 35.7% (5/14), respectively. Hand–foot skin reaction was the most common adverse event in both groups (47.1% (8/17) vs 35.7% (4/140), respectively). No major complications of local therapies were observed in both groups. Conclusions: Regorafenib+PD-1 combined with local therapy as the second-line treatment option for advanced HCC may be effective and safe and provides better benefits than regorafenib+PD-1 alone.
Effect on in-hospital outcomes of patients with hepatocellular carcinoma on aspirin.
Authors: Dhaliwal Armaan , Sohal Aalam , Chaudhry Hunza , Singh Ishandeep , Sharma Raghav , Dukovic Dino , Kalra Shivam , Arora Kirti , Bains Kanwal , Somasundar Ponnandai Sadasivan
Published: June 2023

e16162

Background: Despite the use of new immunotherapies, hepatocellular carcinoma (HCC) has a poor survival rate. Through multiple molecular mechanisms, aspirin (ASA) has demonstrated a reduced incidence of HCC, however, the impact of long-term aspirin use on in-hospital outcomes has not been studied. Methods: We queried the National Inpatient Sample (NIS) database from 2016 to 2020 to identify patients with HCC. Patients were stratified into two groups, based on long-term aspirin use. Information was collected regarding patient demographics, Elixhauser comorbidities, interventions, etiology and decompensations of the liver disease. Outcomes studied included sepsis, shock, acute kidney injury, ICU admission, and in-hospital mortality. The association between long-term aspirin use and outcomes was studied using multivariate analysis. Results: 224,735 patients were included in the study. Of them, 18,835 (8.4%) patients were on long-term aspirin. The majority of the patients with ASA use were White (61.3%), men (78.2%), and aged > 65 years old (68.8%). Patients in the ASA group had a higher incidence of NASH and decreased rates of hepatic decompensation than those not on ASA. Patients with aspirin use had lower incidence of sepsis (2.76% vs 3.54%), shock (4.86% vs 8.23%), AKI (30.9% vs 33.4%), ICU admission (3.88% vs 7.4%) and in-hospital mortality (5.18% vs 9.87%). After adjusting for confounding factors, ASA use was associated with a 30% lower risk of in-hospital mortality (aOR-0.70, 95% CI-0.60-0.82, p<0.001). ASA users also had a 21% lower odds of developing shock (aOR-0.79, 95% CI-0.67-0.94, p-0.007) and 31% lower odds of requiring ICU admission (aOR-0.69, 95% CI-0.54-0.78, p<0.001). No statistically significant difference was noted in the risk of sepsis and AKI between the two groups. Conclusions: Our study noted that patients on long-term aspirin use had better in-hospital outcomes such as mortality, shock and ICU admissions compared to non-aspirin users. These findings are of interest, and further randomized clinical trials confirming the benefits of aspirin in improving outcomes in HCC patients need to be conducted. [Table: see text]
Donafenib combined with hepatic artery infusion chemotherapy (HAIC) and sintilimab for unresectable hepatocellular carcinoma (uHCC): A prospective, single-arm phase II trial (DoHAICs study).
Authors: Zhang Wei , Gao Wei , Liu Chen , Li Guangtao , Zhang Qin
Published: June 2023

e16165

Background: The combination of anti-angiogenesis and immune checkpoint inhibitors has been proved to improve clinical outcomes of uHCC, but efficacy still does not meet clinical needs. In Phase III study (ZGDH3), donafenib showed the survival benefit and better safety compared with sorafenib. HAIC significantly improved treatment responses over TACE in patients with large uHCC in a Phase III trial. Considering the different mechanisms, this study aimed to investigate the safety and efficacy of HAIC combined with donafenib and sintilimab in patients with uHCC. Methods: This is a prospective, single-arm phase II study (NCT05166772). Patients with histologically diagnosed uHCC, no previous systemic treatment, Child-Pugh A5-B7, ECOG performance status (PS) of 0 or 1 were eligible for inclusion. Enrolled patients received donafenib (200 mg, bid), sintilimab (200 mg, q3w) and HAIC (oxaliplatin 85 mg/m2 2h, leucovorin 400 mg/m2 2h, fluorouracil bolus 400 mg/m2 in the first 10 minutes, and fluorouracil infusion 1200 mg/m2 for 23 hours, q3w) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Results: From December 2021 to December 2022, 24 patients (19 men and 5 women; median age, 58 years) were enrolled: BCLC stage A/B/C: 2/9/13; Child-Pugh class A/B: 23/1; ECOG PS 0/1: 23/1. There were 19 (79.2%) pts with hepatitis B. The median tumor size was 7.9 cm (range, 1.7-16.3), 45.8% pts presented macro vascular invasion, the invasion rates of Vp3, Vp4 and inferior vena cava were 25.0%, 4.2% and 8.3% respectively, 16.7% had extrahepatic metastasis. As of February 10, 2023, the median follow-up time was 107 days, the median number of HAIC was 3 times (range, 1-8). Based on mRECIST, the ORR was 78.3% (95% CI, 56.3%-92.5%) with 3 (13.0%) complete responses (CR) and 15 (65.2%) partial responses (PR). The disease control rate (DCR) was 95.7% (95% CI, 78.1%-99.9%). Of 23 pts evaluable for response, the conversion success rate was 65.2% (15/23), 10 of them (43.5%) received hepatectomy, 3 cases (30.0%) achieved complete pathological response and 5 cases (50.0%) achieved major pathological response. The median time to response (TTR) was 1.9 months (range, 1.2-5.2). The median progression-free survival (PFS) was 10.2 months (95% CI, NR) and 6 months PFS rate was 89.1%. The median duration of response (DoR) was not reached. Any grade treatment-emergent adverse events (TEAEs) occurred in 95.8% of pts. The most common TEAEs were thrombocytopenia (66.7%), neutropenia (45.8%), rash (41.7%). Grade 3-4 TEAEs occurred in 37.5% of pts. No grade 5 TEAEs were observed. Conclusions: Preliminary analysis showed that donafenib combined with HAIC and sintilimab showed promising clinical benefits and acceptable toxic effects in patients with uHCC. The enrollment and follow-up are continuing. Clinical trial information: NCT05166772 .
Efficacy and safety of regorafenib alone or in combinations in the second-line setting for advanced hepatocellular carcinoma: A multicenter real-world study.
Authors: Zhang Wei , Zhao Yanrong , Ma Guixiang , Zhang Yu , Guo Yuan , Chen Zhong
Published: June 2023

e16172

Background: Due to drug resistance or intolerable adverse events, most hepatocellular carcinoma (HCC) patients tend to experience TKI-based first-line therapy failure. However, there is no unified choice of second-line treatment after this. Different authors have demonstrated that the combination of regorafenib and PD-1 inhibitors or TACE depicts synergistic effect. Therefore, the major goal of this research is to explore the efficacy and safety of regorafenib alone or in combinations as second-line therapy for advanced HCC in a real-world setting. Methods: In this study 94 advanced HCC patients (84 male and 10 females, average age of 59.8 years) were included from 3 Chinese centers between September 2018 and August 2022. It includes pathologically or clinically diagnosed advanced HCC patients who received regorafenib alone or in combinations in the second-line setting for at least 28 consecutive days. The primary endpoints were objective response rate (ORR, mRECIST criteria), and progression-free survival (PFS), however, the secondary endpoints included overall survival (OS) rate at 12-month, disease control rate (DCR) and treatment-related adverse events (TRAEs). Statistical analysis was performed with Kaplan-Meier method by using log-rank test. Results: 32 (34.0%) patients had BCLC stage B (others had BCLC stage C) and 72 (76.6%) patients were of Child-Pugh A (others were of Child-Pugh B). Half of the patients received regorafenib 160mg once daily during weeks 1–3 of each 4-week cycle. The proportions of patients received single drug regorafenib therapy (REGO) and combination therapies (COM) were 26.6% and 73.4%, respectively. The combination treatment regimens included regorafenib plus PD-1 inhibitors (36.2%), regorafenib combined with TACE (11.7%), and triple therapy (regorafenib, PD-1 inhibitors, TACE) (25.5%). The ORR and DCR were 28.7% and 72.3% with a median PFS of 8.4 months (range 6.33-10.47) and 12-month OS rate was 92.6%. The median PFS of COM group was 8.7 months ranging from 7.09-10.32, which was significantly longer compared to REGO group (4.2 months, range 0.45-7.95) (P = 0.031). Moreover, 66 (70.2%) recipients had TRAEs and most frequent TEAEs (≥5%) included hand-foot syndrome (31.9%), diarrhea (20.2%), rash (13.8%), fatigue (7.4%), oral mucositis (7.4%) and arthralgia (5.3%). 12 (12.8%) recipients had grade 3 TRAEs, including hand-foot syndrome (8.5%), hypertension (2.1%), diarrhea (1.1%) and rash (1.1%). No Grade 4 TRAE and new safety signal were identified. Conclusions: In the second-line treatment of advanced HCC, regorafenib alone or in combinations is effective and well-tolerated. The combination therapy showed a longer survival than regorafenib alone.
Efficacy and safety in unresectable hepatocellular carcinoma using atezolizumab plus bevacizumab in later-line: A retrospective analysis of real-world evidence.
Authors: Cheng Jiamin , Chen Bowen , Zhang Xinfeng , Su Guodong , Peng Caiyun , Zhou Lin , Lei Jin , Li Yinyin , Lu Yinying
Published: June 2023

e16173

Background: As far, no data has been published about later-line application of atezolizumab plus bevacizumab (T+A) in patients with unresectable hepatocellular carcinoma (uHCC). Methods: We retrospectively recruited uHCC patients who treated with later-line T+A. Efficacy endpoints included overall survival (OS) and progression free survival (PFS), in accordance with RECIST v1.1. Safety was evaluated with CTCAE v5.0. We also continually enrolled uHCC patients who received later-line regorafenib plus PD-1 inhibitors (Reg+PD-1) as a comparison. Results: Total 33 patients were continually included, 12 used T+A and 21 chose Reg+PD-1. Baseline performance status, liver function and BCLC tumor stage were similar between two cohorts. At data cut-off at February 2023, following median following-up at 18.9 months, median OS in cohort T+A and Reg+PD-1 were 8.2 (95%CI: 5.8-10.6) vs 15.6 (95%CI: 7.6-23.6) (p = 0.237). Median PFS in cohort T+A and Reg+PD-1were 5.1 (95%CI: 1.1-9.1) vs 3.5 (95%CI: 2.1-4.9) (p = 0.575). OS rate and PFS rate are listed. None of efficacy endpoints reached statistical difference. All patients suffered from AEs. No AEs-related death occurred. Conclusions: Efficacy and safety of later-line T+A in uHCC patients was similar with those who used regorafenib plus PD-1 inhibitors, which needed to be further confirmed. [Table: see text]
Comparison of Child-Turcotte-Pugh score and albumin bilirubin index score for advanced hepatocellular carcinoma at an LMIC tertiary cancer facility.
Authors: Sinha Nishant , Porwal Jasmine , Sehrawat Amit , Mitra Ruchi , Gargy Sumedha
Published: June 2023

e16174

Background: Liver cancer, most commonly HCC, ranks third in cancer-related deaths. Hepatic dysfunction is a key factor in management. BCLC Staging uses CTP Score with objective biosynthetic and subjective parameters as ascites and encephalopathy. Albumin-bilirubin Index (ALBI) grade is an objective method of assessing hepatic dysfunction. Many studies have validated its predictive accuracy. The present study is an attempt to study the clinical profile, risk factor and to compare ALBI with CTP Score as a predictive marker of hepatic function in HCC. Methods: This is a prospective observational study from Feb 2022-Jan 2023. Patients with suspected HCC had physical examination and relevant lab investigations. Diagnosis is established with either appropriate imaging with raised AFP or by Histopathology. ECOG PS, CTP score, ALBI Grade, and BCLC Stage of HCC were assigned. Patients were treated accordingly and are being actively followed. The data was analysed using SPSS with appropriate statistical tests to study their clinical profile and the correlation between the two prognostic scores. Results: There were 54 new patients of HCC with 78.6% being males. Mean age of presentation was 60.88±10.6 yr, with majority had abdominal pain and distension. 78% were diagnosed on imaging with raised AFP. 31 had viral hepatitis with 19 having hepatitis B, and 12 Hepatitis C. 2 were HIV+ with Hepatitis B. 50% were alcoholic. 4 patients had active autoimmune conditions with 2 having RA, 1 had AIH and 1 having AS. 75% had cirrhosis with the majority having>50% liver involvement,61% having portal vein and bile duct invasion. 10,28, and 11 patients belonged to CTP class A,B and C respectively. 57% fell to BCLC Stage 3. 5,21,28 patients belonged to ALBI Grade 1,2 and 3 respectively. The higher ALBI Index had poorer biochemical, radiological profiles and BCLC Stages, signifying the similarity in prognostic severity. Positive correlation found between the CTP score and the ALBI grade (r=0.339; P Value=0.012). Conclusions: The above study concluded ALBI Index as a good prognostic tool for HCC management in low and middle-income countries. It has only 2 biochemical parameters, can easily be done on a single visit and as it correlates significantly with CTP Score.[Table: see text]
A retrospective study on the efficacy and safety of regorafenib alone or in combination in advanced hepatocellular carcinoma.
Authors: Fu Shouzhong , Chen Cong , Zhao Suming , Dai Feng , Yuan Hongxin , Gu Weiwei , Gu Zhuxin , Shi Rongfeng , Jia Pengfei , Lu Xiaohua , Chen Kang , He Ning , Zhao Hui
Published: June 2023

e16176

Background: The earlier randomized phase III RESORCE trial and several real-world studies demonstrate that regorafenib improves overall survival (OS) in advanced hepatocellular carcinoma (HCC). This study aims to evaluate the efficacy and safety of regorafenib alone or in combinations in advanced HCC. Methods: 60 Patients with pathologically or clinically diagnosed advanced HCC were enrolled. We retrospectively analyzed the efficacy and safety of patients who received at least one cycle of regorafenib between March 7, 2019 and December 25, 2022 in the Affiliated Hospital of Nantong University and Nantong Third People's Hospital. The primary endpoints were objective response rate (ORR) and progression free survival (PFS). The secondary endpoints were overall survival (OS), disease control rate (DCR), and safety. The safety and efficacy were assessed by investigators per CTCAE v5.0 and mRECIST v1.1, respectively. Data on survival rates were calculated using the Kaplan-Meier method. Results: The average age was 62.63 years, and 95% were male. Most patients had a Child-Pugh A score (73.3%), and the proportion of patients with BCLC stage B and C classes were 41.7% and 58.3%, respectively. 3 (5%) patients received single-drug regorafenib therapy, and the remaining patients (95%) received different combination therapies, including regorafenib plus immune checkpoint inhibitors (ICIs) (10%), regorafenib combined with TACE (40%), and triple therapy (TKI, ICI, TACE) (45%). The ORR and DCR were 40% and 92%, respectively. With a median follow-up of 16.10 months (95%CI, 11.067-21.133), the median PFS was 8.4 months (95% CI, 5.597-11.203), and the median OS has not been reached. Most patients tolerated 120mg or 160mg once daily during weeks 1–3 of each 4-week cycle. 23 patients (38.33%) experienced adverse events (AEs). The most frequent AE (≥5%) included hand-foot syndrome (23.33%), diarrhea (11.67%), and fatigue (6.77%). The incidence of grade 3 AE was 3%. No grade 4 AE and new safety signals were identified. Conclusions: Regorafenib alone or in combination had a manageable safety profile and promising efficacy in advanced HCC patients.