tbuckley/cabot-search huggingface dataset:
Efficacy and safety in advanced hepatocellular carcinoma between patients with negative and positive APF treated with targeted and immunotherapy.
Authors: Jiamin Cheng, Shuyue Gao, Tianlan Zhang, Pingping Li, Lingxiang Yu, Yinyin Li, Bo Tu, Meiru Song, Shuang Li, Yuebo Ren, Yinying Lu
Journal: Journal of Clinical Oncology (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&gt; 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&lt; 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&gt; 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&gt; 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.
Transcatheter arterial chemoembolization combined with immune checkpoint inhibitors plus bevacizumab or lenvatinib in hepatocellular carcinoma: Results from a retrospective dual-center cohort study.
Authors: Yi Jiang, Mingzhi Shu, Zheng Yao, Weiren Liang, Jiayi Sheng, Yinan Ding, Jiaping Zheng, Guoliang Shao, Junjie Mao, Jun Luo
Journal: Journal of Clinical Oncology (2024)

e16159 Background: Hepatocellular carcinoma (HCC) ranks as the sixth most prevalent cancer worldwide. Notably, over 80% of HCC cases are diagnosed at an intermediate to advanced stage. Transcatheter arterial chemoembolization (TACE) is globally acknowledged as the standard local treatment for intermediate HCC and remains the predominant care for advanced HCC, While lenvatinib (LEN) or the combination of bevacizumab (BEV) and atezolizumab is recognized as a first-line systemic therapy for HCC. Moreover, TACE+LEN+immune checkpoint inhibitors (ICIs) in the treatment of HCC significantly enhances OS and PFS compared to the TACE+LEN. However, comparative studies between TACE+ICI+BEV and TACE+ICI+LEN are still forthcoming. Methods: This retrospective study encompasses data from 64 patients diagnosed with intermediate to advanced unresectable HCC at two medical centers in China between January 2021 and June 2023. The study's primary outcomes were overall survival (OS) and progression-free survival (PFS), while secondary outcomes included tumor response and conversion rates. Additionally, the study assessed the safety by adverse events (AE) across the two groups. Results: Of the 64 enrolled patients, 31 were treated with TACE+ICI+BEV and 33 with TACE+ICI+LEN. There was no significant difference in PFS between the two groups (5.7 months [95% confidence interval (CI) 5.2 to 7.9] versus 4.9 months [95% CI 4.5 to 7.7], P=0.404). The median OS for the TACE+ICI+LEN group was 21.3 months (95% CI 15.1 to 27.5), whereas the median OS in TACE+ICI+BEV group was not reached. A markedly higher proportion of patients in the TACE+ICI+BEV group achieved surgical conversion (22.6% versus 3.0%, P=0.047). Patients presenting with an alanine aminotransferase (ALT) level ≤40 u/L (hazard ratio [HR]=5.61, 95% CI 1.09-28.80, P=0.039) and without hepatic vein invasion (HR=31.6, 95% CI 1.03-9.68, P=0.044) appeared to derive greater benefit from the TACE+ICI+BEV regimen. Furthermore, patients with a Child-Pugh score of class A exhibited enhanced response to the triple-combination therapy (HR=6.17, 95% CI 1.86-20.53, P=0.003). Both therapeutic strategies were characterized by favorable safety profiles. Conclusions: TACE+ICI+BEV has demonstrated notable potential in increasing surgical conversion rate in the management of intermediate to advanced HCC, suggesting enhanced outcomes particularly in patients with superior liver function. [Table: see text]
A real-world experience of hepatic arterial infusion chemotherapy combined with tislelizumab and lenvatinib for unresectable hepatocellular carcinoma with type IV portal vein tumor thrombus.
Authors: Xiaowei Li, Kunkun Cao, Zhigang Fu, Jiaming Zhong, Li Liu, Xiaoxia Chen, Ning Ding, Xiaoli Zhang, Zengqiang Qu, Jian Zhai
Journal: Journal of Clinical Oncology (2024)

e16154 Background: Clinical improvement of interventional therapy with PD-(L)1 inhibitors plus molecular targeted therapies in have been confirmed by several studies, such as EMERALD-1, CHANCE001 etc. Limited data of this treatment in unresectable hepatocellular carcinoma (uHCC) patients (pts) with type IV portal vein tumor thrombus (PVTT) is available. This study aims to describe the efficacy and safety in uHCC pts with type IV PVTT (Vp4) who received HAIC combined with tislelizumab and lenvatinib (HAIC+Tisle+Len) in the real-world setting. Methods: This was a single-center, retrospective analysis of Vp4 uHCC pts treated with HAIC+Tisle+Len as first line systemic therapy between Apr 2020 and Dec 2022. Patient characteristics, treatment information, adverse events and survival data were collected. Pts received HAIC of modified FOLFOX (oxaliplatin, 85 mg/m 2 ; leucovorin, 400 mg/m 2 ; 5-fluorouracil bolus, 400 mg/m 2 on day 1; 5-fluorouracil infusion, 2400 mg/m 2 for 46 h), lenvatinib (8 or 12 mg once daily for body weight, 60 or ≥60 kg), and tislelizumab (200 mg q3w). HAIC was allowed to repeat on demands. Outcomes evaluated included overall survival (OS), progression free survival (PFS), overall response rate (ORR), overall disease control rate (DCR), and treatment-related adverse events (TRAEs). Results: A cohort of 54 pts was identified with a median age of 55 years (range 49-59). Pts characteristics were as follows: male (90.7%), hepatitis B (79.6%), BCLC C stage (100%), Child-Pugh A (88.9%), tumor number [ = 1 (50%), = 2 (7.4%), ≥3 (42.6%)], tumor diameter ≥10 cm (42.6%), extrahepatic metastasis (7.4%), beyond up to steven status (90.7%). As of Dec 20, 2023, the median follow-up duration was 21.3 mo (95% CI, 16.1-26.0), and the median number of HAIC was 3 (range 2-4). The median PFS was 8.1 months (95% CI, 6.8-12.3), while the median OS reached 16.8 months (95% CI:13.1-NR). ORR was 53.7% (3 CR, 26 PR) per RECIST 1.1; ORR was 66.7% (12 CR, 24 PR) per mRECIST. DCR was 96.3% per either RECIST 1.1 or mRECIST. Two pts received surgical treatment after conversion, one of whom underwent liver transplantation and remains tumor-free. The post-PD therapies after first-line treatment were as follows: Tisle+Len (24.1%), TACE+Tisle+Len (18.5%), Tisle+Len+Radiotherapy (7.4%), HAIC+Tisle+Regorafenib (5.6%), others (18.5%). The most common grade 3-4 TRAEs were hypertension (14.8%), decrease in albumin (11.1%), anorexia (9.3%), leukopenia (9.3%), abdominal pain (7.4%) and AST/ALT elevation (7.4%). Conclusions: The combination of HAIC with tislelizumab and lenvatinib represents a promising efficacy and manageable safety for uHCC pts with Vp4, which supplements the trial data for Vp4-HCC with real world outcomes.
Efficacy and safety of regorafenib plus ICIs as second-line treatment in advanced HCC post-frontline treatment failure: A real-world study from a single center.
Authors: Lingzhan Meng, Hu Li, Peng Yu, Li Cao, Zizheng Wang, Jin Yan, Yanling Shao, Bin Shi, Zhenyu Zhu
Journal: Journal of Clinical Oncology (2024)

e16141 Background: Tyrosine kinase inhibitor or bevacizumab (TKI/Bev) combined with immune checkpoint inhibitors (ICIs) currently represent the preferred frontline therapy for patients with Hepatocellular Carcinoma (HCC). Despite this, clinical evidence guiding therapeutic choice for patients unresponsive to this initial immunotherapy regimen remains scarce. This real-world study aimed to assess the efficacy and safety of regorafenib combined with ICIs in patients with HCC who have exhibited disease progress during treatment with TKI/Bev plus ICIs. Methods: This retrospective analysis encompassed a cohort of patients who transitioned to a combined regimen of regorafenib and immune checkpoint inhibitors (ICIs) after the progression of hepatocellular carcinoma (HCC) following treatment with tyrosine kinase inhibitors (TKIs) or a combination of bevacizumab and ICIs, from January 2019 to November 2023. Key efficacy metrics included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The adverse events (AEs) were systematically classified in accordance with the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0). Results: A total of 37 patients were included; 56.8% were Child-Pugh A and 43.2% were Child-Pugh B. Treatment regimens prior to regorafenib and ICIs were lenvatinib plus ICIs in 83.8% of patients, sorafenib plus ICIs in three patients, apatinib plus ICIs, donafenib plus ICIs, and bevacizumab plus ICIs each in one patient. The ORR was 27.0% (10/37), and the DCR was 92.0% (28/37) according to mRECIST criteria. The median PFS was 7.8 months (95% CI, 6.0-9.6). The 6-month and 12-month PFS rates was 60.6% (95% CI, 46.4-79.2) and 40.0% (95% CI, 26.0%-61.6%). The median OS post-regorafenib and ICIs was 16.3 months, with 12-month and 24-month OS rates of 67.0% and 49.7%, respectively. The median OS since first-line treatment initiation was 35.8 months, with OS rates of 94.4% and 72.3% at 12-month and 24-month since first-line treatment initiation, respectively. Subgroup analysis indicated no statistical significance in median PFS between patients with lung metastasis and those without lung metastasis [3.9 months (95% CI, 3.0-4.8) vs 7.80 months (95% CI, 6.1-9.5); P=0.178], but there was a trend toward survival benefit in patients without lung metastasis. Grade 3-4 adverse events were reported in 16.22% of the patients, with no treatment-related fatalities. Conclusions: Regorafenib with ICIs is a promising and tolerable second-line treatment for advanced HCC after initial therapy failure.
Real-world study of anlotinib monotherapy and combination therapy for unresectable hepatocellular carcinoma.
Authors: Yi Lei, Jingchang He, Shuai Kang, Dingli Liu, Wenxuan Yu, Kunyuan Wang, Huaiyu Chen, Yang Cheng, Yun Zhu
Journal: Journal of Clinical Oncology (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.
A multi-center retrospective study on the efficacy and safety of regorafenib plus immune checkpoint inhibitors with or without TACE as a second-line treatment for advanced hepatocellular carcinoma.
Authors: Jinpeng Li, Jinlong Song
Journal: Journal of Clinical Oncology (2024)

e16147 Background: At present, there are no definitive optimal treatment options for patients with hepatocellular carcinoma (HCC) following first-line treatment failure. To maximize the survival benefit of patients, we compared the efficacy and safety of regorafenib plus immune checkpoint inhibitors (ICIs) with transarterial chemoem bolization (R+ICIs+TACE) versus regorafenib plus ICIs (R+ICIs) as a second-line treatment for patients with advanced HCC. Methods: This retrospective study included patients with advanced HCC from our multicenter who received R+ICIs+TACE or R+ICIs as a later-line therapy from June 2020 to August 2022.Objective response rate (ORR), disease control rate (DCR), median progression-free survival (m-PFS), and safety were evaluated according to the modified Response Evaluation Criteria in Solid Tumors(m-RECIST). Factors affecting PFS and OS were analyzed using a Cox proportional-hazards regression model. Results: A total of 78 patients were included in the study (regardless of first-line treatment), including 48 who received R+ICIs+TACE and 30 who received R+ICIs. The R+ICIs+TACE group had a significantly higher ORR (31.6% vs. 9.8%, P = 0.021), higher DCR (73.8%vs. 45.7%, P = 0.008), longer PFS (median 8.5 vs.3.6 months, P &lt; 0.0001) and and a longer OS (14.6 vs 8.5 months, P = 0.024) than those who received R+ICIs group. Child-Pugh class A6 and B7, R+ICIs and extrahepatic metastasis were found as independent prognostic factors for poor PFS. R+ICIs, a-fetoprotein &gt; 400 ng/mL and Child-Pugh class were noted as independent prognostic factors for poor OS.There was no notable difference in the total incidence of treatment-related adverse effects (TRAEs) (76.8% vs. 71.3%, P = 0.41) and the incidence of grade 3/4 serious adverse effects (6.2% vs. 16.1%, P = 0.21) between the two group. Conclusions: Regorafenib plus ICIs with TACE showed a promising efficacy with favorable safety in HCC patients with PD-1 inhibitor resistance, especially in the standard second line patients.
Update results of anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line treatment for advanced biliary tract cancer: A single-arm, open-label phase II clinical trial.
Authors: Wen-Zhi Guo, Lu-Hao Li, Shishi Qiao, Ren-Feng Li, Weijie Zhang, Wei He, Chang Su, Jie Pan, Shui-Ling Jin, Hong Zong
Journal: Journal of Clinical Oncology (2024)

e16144 Background: Efficacy and prognosis of chemotherapy in first-line setting for patients with advanced biliary tract cancer (BTC) was dismal currently. Recently, PD-1/PD-L1 blockades combined with dual chemotherapy in first-line setting exhibited superior efficacy for patients with BTC. Nevertheless, it's important to highlight that both the TOPAZ-1 and KEYNOTE-966 trials had reported a median OS of less than 13 months. This underscored the necessity for further advancements to meet the demands of clinical practice. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as second-line therapy for patients with BTC. Therefore, this study was designed to explore the efficacy and safety of anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC. Preliminary results were presented at the 2024 ASCO-GI Symposium (Abs 498), the consecutively updated results were presented in this report. Methods: Patients with previously untreated metastatic or locally advanced BTC (ICC, ECC, GBC) were recruited and treated with anlotinib (10mg, po, d1~14, q3w) and TQB2450 (1200mg, iv, d1, q3w) plus nab-paclitaxel (200mg/m 2 , iv, d1, q3w) and cisplatin (60mg/m 2 , iv, d1, q3w) until disease progression or unacceptable toxicity. The predefined sample size was 20. Primary endpoint was ORR and secondary endpoints included safety, DCR, PFS, OS and biomarker explore. Results: From April 2023 to Oct 2023, a total of 20 patients were enrolled. At the data cut-off date (Jan, 2024), the best overall response indicated that there were 12 PR (60.0%), 6 SD (30.0%) and 2 PD (10.0%). Therefore, the preliminary ORR was 60.0% (95%CI: 36.1%-80.9%), DCR was 90.0% (95%CI: 68.3%-98.8%). At the data cut-off date, the preliminary prognostic result exhibited that the median PFS of the 20 pts was 8.31 months (95%CI: NA~NA). Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-emergent adverse events among the 20 patients with the incidence &gt; 30% were leukopenia (80%), peripheral sensory neuropathy (45%) and fever (35%). Common grade ≥3 treatment-emergent adverse events were leukopenia (30%), fever (5%), decreased platelet count (5%), malaise (5%), nausea (5%), stomachache (5%), oral mucositis (5%), vomit (5%), rash (5%) and hypotension (5%). Conclusions: Preliminary results suggested that anlotinib plus TQB2450 combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC exhibited encouraging efficacy and manageable adverse events. The conclusion should be validated in more patients consecutively. Clinical trial information: NCT05812430 .
Comparing the efficacy and safety of TACE combined with donafenib or lenvatinib in the treatment of unresectable hepatocellular carcinoma.
Authors: Ning Wei, Dong Lu, Chunze Zhou, Delei Cheng, Zhengfeng Zhang, Xingming Zhang, Jingkun Xiao, Weifu Lv
Journal: Journal of Clinical Oncology (2024)

e16153 Background: For unresectable Intermediate/Advanced-Stage Hepatocellular Carcinoma (uHCC), the efficacy of TACE monotherapy has been unsatisfactory. Studies have shown that TACE combined with molecular targeted drugs exhibits potential synergistic effects, which can prolong the overall survival (OS) of uHCC patients (pts). Donafenib and lenvatinib are small molecule targeted drugs approved as first-line treatments for HCC. The aim of this study is to evaluate the efficacy and safety of TACE combined with donafenib or lenvatinib in the treatment of uHCC. Methods: A retrospective analysis was conducted on the clinical data of uHCC pts treated with donafenib combined with TACE (Dona-TACE) or lenvatinib combined with TACE (Lenva-TACE) at The First Affiliated Hospital of USTC from January 2018 to October 2022. The OS, progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR) of two groups of pts were evaluated according to the mRECIST, and the incidence of adverse events (AEs) was evaluated using CTCAE 5.0. Pts with complete baseline information and at least one follow-up evaluation were incorporated in the final analysis. Results: A total of 105 pts treated with donafenib and 59 pts treated with lenvatinib met the study criteria. After matching with a 1:1 propensity score, 35 pts in the Dona-TACE group and 35 pts in the Lenva-TACE group were included in this study. The baseline characteristics of the two groups are similar (males, 85.7% vs. 85.7%; ECOG PS of 1, 74.3% vs. 71.4%; Exceeding up-to-seven criteria, 74.3% vs. 62.9%; BCLC stage C, 42.9% vs. 40.0%; Combination immunotherapy, 62.9% vs. 54.3%). There was no significant difference in median OS (29.0 vs. 27.3m, P = 0.748) and median PFS (10.5 vs. 10.3m, P = 0.869) in the Dona-TACE and Lenva-TACE groups. The ORR (85.7% vs. 74.3%, P = 0.969) and DCR (94.3% vs. 97.1%, P = 0.280) of the Dona-TACE and Lenva-TACE group were equivalent. Compared with the Lenva-TACE group, pts in the Dona-TACE group had a lower incidence of grade 3-4 adverse events (any grade, 94.3% vs. 91.4%; grade 3 or 4, 34.3% vs. 57.1%, P &lt; 0.05). Among them, pts in the Dona-TACE group had a lower incidence of proteinuria (any grade, 22.9% vs 42.9%; grade 3 or 4, 0 vs17.1%, P &lt; 0.05) and hypertension (any grade, 42.9% vs 71.4%; grade 3 or 4, 2.9% vs 25.7%, P &lt; 0.05) than those in the Lenva-TACE group. Multivariate analysis showed that ECOG PS score, up-to-seven criteria, and tumor blood supply were independent prognostic factors affecting OS (HR, 3.470, 3.619, 3.067; P &lt; 0.05). Conclusions: The efficacy of donafenib and lenvatinib combined with TACE in the treatment of uHCC is equivalent. Furthermore, compared to lenvatinib combined with TACE, donafenib combined with TACE has higher safety.