bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of triplet regimen (single-agent chemotherapy plus anti-PD-1 antibody and tyrosine kinase inhibitors) on survival compared to chemotherapy in the second-line treatment of advanced biliary tract cancer: A retrospective analysis.
Authors: Yuan Zhengang , Shang Peipei 
Published: July 2024

e16132 Background: TOPAZ-1 and KEYNOTE-966 trials have demonstrated the survival benefit of immune checkpoint inhibitors (ICIs) plus chemotherapy in advanced biliary tract cancer (BTC). Although the ABC‐06 study proved the benefits of FOLFOX in 2nd line therapies, the efficacy is limited. There is no consensus regarding the optimal therapy regimen, and more effective therapeutic options are needed. This retrospective analysis aims to evaluate the efficacy of a triplet regimen compared to standard chemotherapy in 2nd line BTC. Methods: Pts > 18 years, with ECOG PS 0/1, histologically confirmed metastatic BTC and progression on 1st line Gemcitabine-based therapy were eligible. A triple regimen was referred as Cohort A: tislelizumab and other anti-PD-1 antibody, capecitabine or S-1 plus tyrosine kinase inhibitors (TKIs, lenvatinib or anlotinib). Standard chemotherapy was Cohort B: mFOLFOX or irinotecan plus capecitabine. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), overall response rates (ORR), disease control rate (DCR) and safety. Results: This study retrospectively collected and analyzed treatment and clinical information from 121 pretreated BTC pts from Oct. 2021 to Oct. 2023, with a median age of 60 (range 36-82) years and 48% (58) of the pts were female. Among them, 86 patients received the triple regimen, while 35 patients received standard chemotherapy. Pts’characteristics were well balanced between the two groups in terms of gender, age, ECOG score, primary site, CEA, CA199, or presence of distant metastasis. According to the RECIST1.1 criteria, 1 pt achieved CR and 31 pts had PR in the triple treatment cohort, ORR reached 37.2% (95%CI 27.0-48.3%), which was significantly higher than the 2.8% (95%CI 0.1-14.9%) in the standard chemotherapy cohort (p < 0.0001). Accordingly, the DCR of the two groups were 89.5% (95%CI 81.1-95.1%) and 71.4% (95%CI 53.7-85.4%) respectively. As of Oct 31, 2023, all patients developed progression, and the median PFS in cohort A was 6 months, compared to 2.0 months in cohort B (HR, 0.29, 95%CI 0.16-0.52, p < 0.0001). 64 patients of cohort A and 28 patients of cohort B developed death. The median OS in cohort A was 16.0 months, compared to 6.0 months in cohort B (HR 0.35, 95%CI 0.19~0.64, p < 0.0001). Any grade TRAEs occurred in 54.7% pts of cohort A and 42.9% of cohort B. Most common grade 3 TRAEs were hypohepatia (19.8%), hand-foot syndrome (11.6%), gastrointestinal reaction (1.2%) in cohort A, and hypohepatia (8.6%), hand-foot syndrome (2.9%) in cohort B. Conclusions: The retrospective analysis suggests that the triple regimen as second-line treatment for advanced BTC pts may help improve the efficacy and survival, and is worthy of further prospective exploration.
Second-line systematic strategy options for the progression of lenvatinib plus tislelizumab treating unresectable hepatocellular carcinoma: A retrospective study.
Authors: Xiaozhun Huang , Che Xu , Wang Chuling 
Published: July 2024

e16135 Background: Lenvatinib plus Tislelizumab (LEN+TIS) is a first-line systemic treatment for unresectable hepatocellular carcinoma (uHCC) in the real world, however, most uHCC ultimately fail to respond to first-line therapy due to tumor progression or intolerable adverse effects. The progression-free survival (PFS) of Lenvatinib was approximately 8 months in both REFLECT and LEA-002 studies. Therefore, there were doubts about the second-line therapy after progressive disease (PD) of LEN+TIS, and no studies hade reported the specific switching mode. Methods: This study retrospectively analyzed the clinical data of the first-line treatment of uHCC with LEN+TIS in National Cancer Center/Cancer Hospital & Shenzhen Hospital from April 2019 to December 2023. According to the actual use of drugs, Group A changed Lenvatinib to Regorafenib while Tislelizumab was not changed after PD of LEN+TIS; Group B replaced with Regorafenib plus other immune checkpoint inhibitors (including PD-1, PDL-1) after PD of LEN+TIS. The initial dose of Regorafenib was 80 to 160 mg, which could be adjusted according to patient tolerability, with Regorafenib administered orally once daily for the first 3 weeks, every 4 weeks as a cycle; Tislelizumab given 200mg intravenously every 3 weeks. Both group A and B were subdivided into two subgroups based on whether PFS of LEN+TIS had been more than 8 months. Short- and long-term outcomes were assessed by two independent radiologists according to mRESCIST criteria, all statistical analysis was performed using SPSS version 20. Results: After rigorous screening, a total of 446 samples were recruited in this study, including 208 in group A and 238 in group B. The baseline characteristics were comparable between the two groups, all patients were Child-Pugh grade A, and the median follow-up time was 9.8 months. Group A had higher objective response rates (ORR: 31.2%vs26.9%), PFS (7.6vs6.1months), and median overall survival (mOS: 12.8vs11.2months). Subgroup analysis showed that patients in group A who had first-line PFS shorter than 8 months had a better treatment effect than those with first-line PFS longer than 8 months (ORR: 36.9%vs17.7%; DCR:69.2%vs46.8%;PFS: 8.7vs 5.1months; OS: 14.4vs8.9months; P<0.05); patients in group B who were treated with first-line systemic PFS shorter than 8 months was worse than that with first-line PFS longer than 8 months (ORR:12.2%vs38.6%; DCR:45.3%vs68.9%;PFS:5.6vs6.4months;OS:9.1vs12.6months; P<0.05). No new adverse events were observed, no treatment-related deaths occurred in either group. Conclusions: If the PFS of LEN+TIS was shorter than 8 months, Lenvatinib should be changed to Regorafenib, Tislelizumab could be not changed. And if the PFS of LEN+TIS was longer than 8 months, Lenvatinib and Tislelizumab should be changed at the same time, which seemed to achieve better results.
Transarterial chemoembolization combined with donafenib or lenvatinib as first-line treatment for unresectable hepatocellular carcinoma: A single-center real-world retrospective study.
Authors: Liu Huan , Huang Mingsheng 
Published: July 2024

e16137 Background: Combined Transarterial chemoembolization (TACE) with tyrosine kinase inhibitor (TKI) treatment has been proven to be beneficial. This study aimed to retrospectively compare the efficacy and safety of Donafenib (DON)-TACE versus Lenvatinib (LEN)-TACE as first-line treatment for unresectable hepatocellular carcinoma (uHCC). Methods: From May 2020 to May 2023, a retrospective analysis was conducted on the clinical data of 93 patients with previously untreated uHCC who underwent treatment at the department of Interventional Radiology of the Third Affiliated Hospital of Sun Yat-sen University. Among them, 49 were in the DON-TACE group and 44 in the LEN-TACE group. The primary endpoint was progression-free survival (PFS) according to mRECIST, and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety outcome. Results: As of the data cut-off date Aug 26, 2023, the median PFS was 221 days (95% CI 141–366) in the DON-TACE group and 173 days (95% CI 108–215) in the LEN-TACE group (HR = 0.783, 95% CI 0.462–1.325, P = 0.362).ORR and DCR of the DON-TACE group were 55.1% (95% CI 40.23–69.33) and 75.51% (95% CI 61.13–86.66), respectively, while those of the LEN-TACE group were 61.36% (95% CI 45.49–75.64) and 81.82% (95% CI 67.29–91.81). No significant difference was observed either in ORR(P = 0.689) or DCR(P = 0.627) between the two groups. The incidence rates of total adverse events for any grade (85.71% vs 100.00%, P = 0.027) and ≥Grade 3 (22.496% vs 45.45%, P = 0.019) were significantly lower in the DON-TACE group. In addition, the incidence rates of AST increased (27.27% vs 56.82%, P = 0.005), diarrhea (6.12% vs 25.00%, P = 0.011), vomiting (0% vs 40.91%, P < 0.001), proteinuria (0% vs 18.18%, P = 0.011), gastrointestinal hemorrhage (0% vs 13.64%, P = 0.048) and hypertension (2.04% vs 36.36%, P < 0.001) for any grade were also significantly lower in the DON-TACE group. Conclusions: DON-TACE and LEN-TACE showed comparable efficacy as first-line therapies for uHCC patients. DON-TACE demonstrated a lower incidence of severe adverse events.
Real-world study of anlotinib monotherapy and combination therapy for unresectable hepatocellular carcinoma.
Authors: Lei Yi , He Jingchang , Kang Shuai , Liu Dingli , Yu Wenxuan , Wang Kunyuan , Chen Huaiyu , Cheng Yang , Zhu Yun 
Published: July 2024

e16146 Background: Unresectable hepatocellular carcinoma (uHCC) is an aggressive tumor with poor prognosis. Anlotinib is a novel small-molecule tyrosine kinase inhibitor (TKI) that selectively targets VEGFR, FGFR, PDGFR, and c-kit receptors. Clinical trials have confirmed the efficacy and safety of anlotinib monotherapy or anlotinib-based combination therapy for uHCC. However, many patients in clinical practice fail to meet the criteria for these trials. Therefore, this study aimed to investigate the efficacy and safety of anlotinib, as monotherapy or in combination therapy, for uHCC in clinical practice in China. Methods: This multicenter, real-world study enrolled patients with uHCC who had received anlotinib-based therapy, and completed at least one post-treatment efficacy assessment between July 2020 to February 2023. Patients who did not undergo imaging after one cycle of treatment, were lost to follow-up before completing one cycle of treatment, or required systemic chemotherapy or radiotherapy for the primary lesion were excluded from the study. The efficacy assessments were performed based on the RECIST version 1.1. OS, PFS, TTP, DCR and ORR for patients with anlotinib monotherapy (n = 12) and anlotinib-based combination therapy (n = 60) were evaluated. The main statistical analysis was conducted using the Kaplan–Meier method and log-rank test. Subgroup comparisons were performed based on different combinations of anlotinib therapy and the number of treatment lines in patients with uHCC. Occurrence of adverse events (AEs) to evaluate the safety profiles of anlotinib monotherapy or anlotinib-based combination therapy was collected. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire HCC-18 (EORTC QLQ-HCC18) was used to evaluate health-related quality of life (HRQOL). Results: For the anlotinib monotherapy group, the OS, PFS, TTP, DCR and ORR were 14.2 months, 6.9 months, 7.9 months, 16.7%, and 50.0%, respectively. For the anlotinib-based combination therapy group, these values were 15.8 months, 8.6 months, 10.2 months, 25.0%, and 65.0%, respectively. There was no significant difference in OS, PFS, and TTP between the two groups. PFS were significantly decreased in the non-first-line treatment group compared to the first-line treatment group. The incidence of drug-related AEs of any grade was 93.1%, with the most common grade ≥3 treatment-related AEs being lymphopenia and elevated transaminases. The time to deterioration was 14.0 months (95%CI: 8.3–19.8) and 12.2 months (95%CI: 9.8–14.7) in the monotherapy and combination therapy groups. Conclusions: Anlotinib demonstrated satisfactory efficacy and safety as a single agent and in combination with other therapies in the treatment of uHCC, with potential benefit on health-related quality of life.
Efficacy and safety in advanced hepatocellular carcinoma between patients with negative and positive APF treated with targeted and immunotherapy.
Authors: Cheng Jiamin , Gao Shuyue , Zhang Tianlan , Li Pingping , Yu Lingxiang , Li Yinyin , Tu Bo , Song Meiru , Li Shuang , Ren Yuebo , Lu Yinying 
Published: July 2024

e16162 Background: Serum alpha-fetoprotein (AFP) is widely accepted as a crucial tool for clinical diagnosis and screening of HCC. However, there are cases where patients test negative for AFP but are confirmed to have Hepatocellular Carcinoma through imaging or pathological examinations. Despite these findings, there is limited research focusing on the medicine selection for AFP-negative patients. Methods: This retrospective cohort study, involving 223 untreated advanced HCC patients, and the first-line regimen consisted of targeted therapy and TKI+ICIs therapy. Patients are categorized into negative and positive AFP groups based on initial serum levels. Main efficacy endpoint was progression free survival (PFS), evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: According to the level of serum AFP, they were divided into negative group(100) and positive group(123). The two groups showed no statistically significant differences in age, gender, Child-Pugh score and other baseline clinical characteristics( P> 0.05). At data cut-off at February 2023, median OS was not matured and mPFS in negative group was higher than positive group(8.2 vs 5.3months, P< 0.0001). In the ICIs+TKI therapy cohort, mPFS in the negative AFP group(52) was significantly higher than in the positive AFP group(70) (10 vs. 5.8 months, P = 0.0021). Considering all patients in the negative AFP group as a subgroup, an analysis of survival benefits between those receiving targeted therapy and those receiving TKI+ICIs therapy revealed no significant difference in PFS( P> 0.05). Moreover, AEs were compared between the negative and positive group, with no significant differences observed in Any Grade or Grade 3/4( P> 0.05). Conclusions: Patients with negative AFP exhibited superior survival benefits compared to those with positive AFP in first-line therapy. Regarding PFS, the TKI+ICIS therapy did not demonstrate a better benefit over targeted therapy in the negative AFP subgroup.
Des-gamma-carboxy prothrombin (DCP) as a prognostic biomarker in patients with advanced hepatocellular carcinoma treated with atezolizumab/bevacizumab.
Authors: Conner Elizabeth , Chang Jeremy , Burgoyne Adam 
Published: July 2024

e16167 Background: Causes of variable disease response to first-line treatment with atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma (HCC) remain unclear. Identifying tumor markers that predict treatment response and provide prognostic information may help clinicians optimize treatment strategies and patient outcomes. The role of des-gamma-carboxy prothrombin (DCP) is not well established in Hepatitis B Virus non-endemic areas. This study aimed to investigate DCP as a predictive biomarker of treatment response as well as explore prognostic implications of DCP in patients with advanced HCC. Methods: This single-center retrospective analysis evaluated DCP and radiographic response in patients with advanced HCC who received atezolizumab/bevacizumab in the first-line setting. DCP was measured at the time of best response, determined by radiographic evaluation, and compared to day one of atezolizumab/bevacizumab initiation. Elevated DCP was defined as > = 7.5 ng/mL. DCP response was defined as a decrease of > = 50% at response assessment compared with baseline. Comparisons of treatment effects were performed using two-tailed Fisher Exact Probability Test. Overall survival (OS) was defined as the interval between the first treatment and either the date of death or the last follow-up visit. OS was analyzed using the Kaplan–Meier method and compared between groups using the log-rank test. Results: A total of 53 patients with advanced HCC treated with atezolizumab/bevacizumab were included. Radiographic treatment responses were complete response 3.8%, partial response 22.6%, stable disease 52.8% and progression of disease 20.8%, respectively. On day one of treatment 70% of patients had an elevated DCP. Patients with DCP response had ORR of 69% (odds ratio, 15.75; 95% CI, 3.50 – 70.9; p = 0.0002) and disease control rate of 100% (p = 0.047). Conversely, patients with > = 50% increase in DCP at response evaluation compared to day one of treatment had ORR of 4.5% and no response rate of 95% (p = 0.0035). Furthermore, patients who had > = 50% increase in DCP had median OS of 15.4 months compared to patients without > = 50% increase in DCP who had median OS of 28.4 months (HR = 2.48; 95% CI, 1.035 – 5.93; p = 0.042). There was no difference in ORR, or OS, between patients who had elevated DCP on day one of treatment and those who did not. Conclusions: DCP response correlates with objective radiographic response in patients with advanced HCC treated with atezolizumab plus bevacizumab in the first-line setting. DCP increase of > = 50% correlates with decreased median OS and may serve as a negative prognostic biomarker in such patients.
Lenvatinib (Lenv) plus tislelizumab (Tis) combined with or without transarterial chemoembolization (TACE) in first-line treatment of unresectable hepatocellular carcinoma (uHCC): A prospective, non-randomized, open-label, phase II cohort study.
Authors: Zhang Nan , Li Jiongyuan , Piao Mingjian , Li Chengjie , Xun Ziyu , Zhang Longhao , Wang Yanyu , Liu Kai , Wang Shanshan , Wang Hanping , Zhao Hai-Tao 
Published: July 2024

e16169 Background: The synergistic potential of programmed death protein-1 inhibitors and tyrosine kinase inhibitors in treating uHCC has been established. TACE, a cornerstone in uHCC therapy, primes the tumor microenvironment for immunotherapy by releasing neoantigens and inducing ischemia. This study explores the efficacy and safety of Lenv plus Tis, combined with or without TACE, in a first-line setting. Methods: This phase II study enrolled patients (pts) with pathologically and/or radiologically diagnosed uHCC eligible for embolization, with at least one measurable lesion, Child-Pugh class A/B, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Pts received Tis (200mg every 3 weeks) and Lenv (oral dose adjusted by weight: 8mg for <60kg and 12mg for ≥60kg) with or without conventional TACE, as determined by the treating physician. The primary endpoint was the objective response rate (ORR), with secondary endpoints including overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). Results: By the data cutoff on January 27, 2024, 37 pts were enrolled: 12 received Lenv+Tis (cohort 1), and 25 received Lenv+Tis+TACE (cohort 2). Median follow-up time was 10.66 months. The ORR was 33.3% in cohort 1 and 68.0% in cohort 2, with DCRs of 100% and 96%, respectively (mRECIST). Median OS was 10.85 months (95% CI, 4.76-16.95) for cohort 1 and 13.61 months (95%CI, NE-NE) for cohort 2. Median PFS was 10.85 months (95% CI, NE-NE) for cohort 1, and 11.86 months (95% CI, 6.49-16.73) for cohort 2. Grade 3-4 treatment-emergent adverse events (teAE) occurred in 50% of cohort 1 and 68% of cohort 2. No fatal adverse event was reported. The most common grade 3-4 teAE (incidence >10%) were anaemia (17%) in cohort 1, and decreased platelet count (16%), hypertension (16%), rash (16%), fatigue (12%), elevated ALT (12%) in cohort 2. Conclusions: Both Lenv+Tis and Lenv+Tis+TACE showed promising efficacy and manageable safety in the first-line treatment of uHCC. More pts were recruiting to further prove these results. Clinical trial information: NCT05842317 . [Table: see text]
Efficacy and safety of TACE combined with ablation and regorafenib for unresectable hepatocellular carcinoma: A real-world study.
Authors: Xiong YiQi , Gao WenFeng , Long Jiang , Hu CaiXia , Yuan ChunWang , Sun Yu , Shi QinSheng , Sun Bin , Zhang YingHua , Cui XiongWei , Hao MeiJun , Li Jianjun , Zhang Yonghong 
Published: July 2024

e16170 Background: The purpose of our study was to determine the efficacy and safety of transarterial chemoembolization (TACE) combined with regorafenib as second-line therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods: Patients with HCC at Barcelona Clinic Liver Cancer (BCLC) stage B or C who received the combined treatment of TACE, ablation, and regorafenib or regorafenib plus anti-PD-1 immune checkpoint inhibitors (ICIs) in Youan hospital between April 2020 to June 2023 were reviewed. The primary end-point was progression-free survival (PFS). Overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity were the secondary endpoints. Results: A total of 73 patients were enrolled in our study, including 63 (86.3%) males and 10 (13.7%) females. 16 (21.9%) patients had portal vein tumor thrombosis (PVTT) and 33 (45.2%) patients had extrahepatic metastasis. There were 53 (72.6%) patients with multiple tumor numbers and 23 (31.5%) patients with large tumors (≥30mm). All patients received TACE combined with regorafenib, while 37 (50.7%) patients plus ICIs and 36 (49.3%) patients not plus with ICIs. Besides, the majority of patients (N=61, 83.6%) in our cohort received ablation. The patients with AFP>400U/L were 22 (20.1%). The average follow-up of the cohort was 24.6 months. The median PFS was 7.06 months (95%CI: 4.77-9.36 months) and the median OS was 23.47 months (9.79-37.15 months). Treatment response is shown in Table 2. According to mRECIST criteria, the ORR was 58.9% and the DCR was 91.8%, respectively. No adverse effects (AEs) were reported in the 11 patients in the study. The most common any-grade treatment-related AEs were hand-foot syndrome (21.9%), diarrhea (23.28%), and hypertension (21.9%). Grade≥3 treatment-related AE occurred in 12.3% of the patients. The most common grade 3 treatment-related AE was hypertension (5.48%). Conclusions: TACE combined with ablation and regorafenib is an effective, safe, and promising second-line treatment option for patients with unresectable HCC after progression from first-line therapy. [Table: see text]