Immune Checkpoint Inhibitors versus VEGF Targeted Therapy as Second Line Regimen in Advanced Hepatocellular Carcinoma (HCC): A Retrospective Study

Several targeted agents including multi-tyrosine kinase inhibitors (mTKIs) and immunotherapy (IO) agents have been approved for use beyond the frontline setting in patients with advanced hepatocellular carcinoma (HCC). Due to lack of prospective head-to-head comparative trials, there is no standardized way for alternating those agents beyond frontline. Therefore, we performed a retrospective review of the Kansas University (KU) cancer registry to determine whether IO may be superior to non-IO therapy. Patients with advanced HCC were divided into two groups based on the second-line systemic regimen received (IO vs. non-IO). Progression-free survival (PFS) and overall survival (OS) were calculated under the Kaplan–Meier and Cox proportional hazards models. No statistically significant differences in PFS and OS were found, although a non-significant delayed separation in the survival curve favoring IO was identified (median PFS 3.9 months vs. 3 months; median OS 10 months vs. 10 months respectively for IO vs. non-IO). This retrospective analysis is one of the earliest and largest studies comparing second-line IO and non-IO therapies thus far reported. Future studies should aim to define specific biomarkers for response prediction and treatment optimization based on individual patient and tumor characteristics. Furthermore, combinatorial therapeutic strategies is an evolving approach showing early promising signal.

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Changing paradigm in oncology clinical trials: Cox-TEL—Adjustment made ready for early crossover and tail tale.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15067 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15067-e15067

Author(s):

Emily Pei-Ying Lin ◽

Chih-Yuan Hsu ◽

Pan-Chyr Yang ◽

Yu Shyr

Keyword(s):

Proportional Hazards ◽

Checkpoint Inhibitors ◽

Survival Curve ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Poor Responders ◽

Term Survival ◽

Study Results ◽

Before And After ◽

Oncology Clinical Trials

e15067 Background: Approvals of immune checkpoint inhibitors (ICI) were made based on positive clinical trial results analyzed by the Cox proportional hazards (PH) model. With ICI data, however, long tails and early crossover in survival curves, which violate the Cox PH assumption, can lead to misinterpretation of clinical significance of findings. Here we introduce the Cox-TEL and show the differences of study results before and after Cox-TEL adjustment using KEYNOTE 042 and 045 as examples. Methods: Cox-TEL is built on the mathematical foundation of Taylor expansion. As an easily implemented alternative of PH cure model, it not only infers associations between survival probabilities of the two study arms among patients without long-term survival (poor-responders), but also estimates differences in proportion (DP) between arms among patients in the long-tail segment of the survival curve (true-responders). Results: In KEYNOTE 042, the Cox-TEL HRs for death were statistically insignificant across all subgroups. The trend of DP, on the other hand, is positively related to that of PD-L1 TPS and inverted related to that of Cox HR when the PD-L1 ≥50% cohort is covered. In KEYNOTE 045, the Cox-TEL HRs suggested that for the poor-responders, pembrolizumab did not do better than chemotherapy in terms of overall survival (OS) and might do harm to the patients in terms of progression-free survival (PFS). For the true-responders, DPs of OS and PFS were both statistically significant (Table). Conclusions: Our data demonstrated the biases derived from insufficient data analyses and strengthened the necessity of analytic model revisits in the new oncology era of which cure for advanced cancers is no longer impossible. [Table: see text]

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Anlotinib in the treatment of advanced hepatocellular carcinoma: an open label phase II study (ALTER-0802 study)

10.21203/rs.3.rs-229677/v1 ◽

2021 ◽

Author(s):

Yongkun Sun ◽

Aiping Zhou ◽

Wen Zhang ◽

Zhichao Jiang ◽

Bo Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase Ii ◽

Kinase Inhibitors ◽

Progression Free Survival ◽

Advanced Hepatocellular Carcinoma ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

Open Label ◽

Open Label Phase

Abstract Purpose: This study aimed to assess efficacy and safety of anlotinib as a first- or second-line treatment for advanced or metastatic hepatocellular carcinoma (aHCC) and to identify the predictive plasma cytokines on efficacy of anlotinib.Methods: It was a phase II clinical study. Patients with aHCC were recruited from October 2016 to April 2019 and divided into two cohorts according to previous tyrosine kinase inhibitors (TKIs) therapy. Those without or with prior TKIs were in Cohort 1 or 2, respectively. All patients took anlotinib (12mg/day, Day1–14, three weeks per cycle). The primary endpoint was 12-week progression free survival (PFS) rate. Relationship between series plasma cytokine level and efficacy of anlotinib was analyzed.Results: Enrolled 26 patients in Cohort 1 and 24 in Cohort 2. In Cohort 1, the 12-week PFS rate was 80.8% (95% confidence interval [CI]; 59.8%–91.5%) and median time to progression (TTP) was 5.9 months (95% CI; 4.8–6.9). In Cohort 2, the 12-week PFS rate and median TTP was 72.5% (95% CI; 48.7%–86.6%) and 4.6 months (95% CI; 2.7–10.0), respectively. The median TTP on patients with baseline plasma level of CXCL1 (C-X-C motif chemokine ligand 1) less than 7.6 ng/μl was significant longer in both cohorts. The most common grade 3–5 adverse events were hypertension (8%), diarrhea (8%) and hand-foot syndrome (6%). Conclusion: Anlotinib showed promising efficacy and safety as a first- or second-line treatment with a continuous TKIs treatment strategy in aHCC. The plasma CXCL1 might be a predictor for efficacy of anlotinib.

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Anlotinib in the treatment of advanced hepatocellular carcinoma: an open-label phase II study (ALTER-0802 study)

Hepatology International ◽

10.1007/s12072-021-10171-0 ◽

2021 ◽

Author(s):

Yongkun Sun ◽

Aiping Zhou ◽

Wen Zhang ◽

Zhichao Jiang ◽

Bo Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase Ii ◽

Kinase Inhibitors ◽

Progression Free Survival ◽

Advanced Hepatocellular Carcinoma ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

Open Label ◽

Open Label Phase

Abstract Purpose This study aimed to assess efficacy and safety of anlotinib as a first- or second-line treatment for advanced or metastatic hepatocellular carcinoma (aHCC) and to identify the predictive plasma cytokines on efficacy of anlotinib. Methods It was a phase II clinical study. Patients with aHCC were recruited from October 2016 to April 2019 and divided into two cohorts according to previous tyrosine kinase inhibitors (TKIs) therapy. Those without or with prior TKIs were in Cohort 1 or 2, respectively. All patients took anlotinib (12 mg/day, Day1–14, 3 weeks per cycle). The primary endpoint was 12-week progression-free survival (PFS) rate. Relationship between the series plasma cytokine level and the efficacy of anlotinib was analyzed. Results Enrolled 26 patients in Cohort 1 and 24 in Cohort 2. In Cohort 1, the 12-week PFS rate was 80.8% [95% confidence interval (CI); 59.8%–91.5%] and median time to progression (TTP) was 5.9 months (95% CI 4.8–6.9). In Cohort 2, the 12-week PFS rate and median TTP was 72.5% (95% CI 48.7%–86.6%) and 4.6 months (95% CI 2.7–10.0), respectively. The median TTP on patients with a baseline plasma level of CXCL1 (C-X-C motif chemokine ligand 1) less than 7.6 ng/μl was significantly longer in both cohorts. The most common grade 3–5 adverse events were hypertension (8%), diarrhea (8%) and hand-foot syndrome (6%). Conclusion Anlotinib showed promising efficacy and safety as a first- or second-line treatment with a continuous TKIs treatment strategy in aHCC. The plasma CXCL1 might be a predictor for the efficacy of anlotinib.

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

Oncology ◽

10.1159/000516671 ◽

2021 ◽

pp. 1-7

Author(s):

Oded Jacobi ◽

Yosef Landman ◽

Daniel Reinhorn ◽

Oded Icht ◽

Michal Sternschuss ◽

...

Keyword(s):

Diabetes Mellitus ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Proportional Hazards ◽

Checkpoint Inhibitors ◽

Negative Relationship ◽

Progression Free Survival ◽

Significant Negative Correlation ◽

Cox Proportional Hazards ◽

Diabetic Patients

Introduction: Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. Methods: All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, t tests, and χ2 tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. Results: Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01–2.06], p = 0.011, and HR 1.5 [1.08–2.08], p = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61–1.93], p = 0.79, and HR 1.29 [0.69–2.39], p = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. Conclusion: Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.

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Immune Checkpoint Inhibitors as Monotherapy or Within a Combinatorial Strategy in Advanced Hepatocellular Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms21176302 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6302

Author(s):

Michela Guardascione ◽

Giuseppe Toffoli

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trials ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Kinase Inhibitors ◽

Checkpoint Inhibitors ◽

Target Therapy ◽

Antiangiogenic Agents ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Hcc

In advanced-stage hepatocellular carcinoma (HCC), systemic treatment represents the standard therapy. Target therapy has marked a new era based on a greater knowledge of molecular disease signaling. Nonetheless, survival outcomes and long-term response remain unsatisfactory, mostly because of the onset of primary or acquired resistance. More recently, results from clinical trials with immune targeting agents, such as the immune checkpoint inhibitors (ICIs), have shown a promising role for these drugs in the treatment of advanced HCC. In the context of an intrinsic tolerogenic liver environment, since HCC-induced immune tolerance, it is supported by multiple immunosuppressive mechanisms and several clinical trials are now underway to evaluate ICI-based combinations, including their associations with antiangiogenic agents or multikinase kinase inhibitors and multiple ICIs combinations. In this review, we will first discuss the basic principles of hepatic immunogenic tolerance and the evasive mechanism of antitumor immunity in HCC; furthermore we will elucidate the consistent biological rationale for immunotherapy in HCC even in the presence of an intrinsic tolerogenic environment. Subsequently, we will critically report and discuss current literature on ICIs in the treatment of advanced HCC, including a focus on the currently explored combinatorial strategies and their rationales. Finally, we will consider both challenges and future directions in this field.

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Real-World Efficacy and Safety of Lenvatinib in Korean Patients with Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis

Liver Cancer ◽

10.1159/000508901 ◽

2020 ◽

Vol 9 (5) ◽

pp. 613-624 ◽

Cited By ~ 2

Author(s):

Jaekyung Cheon ◽

Hong Jae Chon ◽

Yeonghak Bang ◽

Neung Hwa Park ◽

Jung Woo Shin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Retrospective Analysis ◽

Real World ◽

Checkpoint Inhibitors ◽

Clinical Trial Data ◽

Progression Free Survival ◽

Phase Iii ◽

Advanced Hepatocellular Carcinoma ◽

Efficacy And Safety ◽

First Line

Introduction/Objective: Lenvatinib demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the randomized phase III REFLECT trial. Considering the discrepancies in patients between clinical trial data and daily practice, an account of practical experience is needed. Methods: We conducted a multicenter retrospective analysis in which 3 tertiary referral centers participated. A total of 92 patients with advanced HCC treated with lenvatinib between September 2018 and January 2020 were analyzed. Results: Lenvatinib was used as the first-line therapy for 67 (72.8%) patients, and for 25 (27.2%) patients previously treated with other systemic therapy including immune checkpoint inhibitors. At the time of initiation of lenvatinib, 74 (80.4%) and 18 (19.6%) patients were classified as Child-Pugh A and B, respectively. Thirty-five patients (38.0%) had extensive disease that would have excluded them from the REFLECT trial. In the Child-Pugh A group, the response rate graded according to the Response Evaluation Criteria in Solid Tumors v1.1 was 21.1%, median progression-free survival (PFS) was 4.6 (95% confidence interval [CI] 3.1–6.1) months, and overall survival (OS) was 10.7 (95% CI 4.8–16.5) months for patients treated with first-line lenvatinib (n = 57). With second- or later-line lenvatinib (n = 17), median PFS and OS were 4.1 (95% CI 3.1–5.1) and 6.4 (95% CI 5.1–7.7) months, respectively. In the Child-Pugh B group (n = 18), median PFS and OS were 2.6 (95% CI 0.6–4.6) and 5.3 (95% CI 2.0–8.5) months, respectively. The most common grade 3–4 toxicities were hyperbilirubinemia (n = 8; 8.7%), AST elevation (n = 6; 6.5%), and diarrhea (n = 5; 5.4%) across all study patients. Conclusions: In this real-world study, lenvatinib was found to be well tolerated and effective in more heterogeneous HCC patient populations.

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Pharmacogenetic analysis in metastatic colorectal cancer (mCRC) patients (pts) treated with second-line irinotecan (IR)+/− cetuximab (CB): The EPIC experience

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4022 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4022-4022

Author(s):

D. Yang ◽

A. Pohl ◽

W. Zhang ◽

G. Lurje ◽

Y. Ning ◽

...

Keyword(s):

Proportional Hazards ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Phase Iii ◽

Rank Test ◽

Second Line ◽

Ca Repeat ◽

Ras Mutation ◽

Mutation Status ◽

Log Rank Test

4022 Background: EPIC, a multinational phase III clinical trial with IR + CB vs IR alone in mCRC pts in the second-line setting after failure of FOLFOX demonstrated a benefit for IR+CB in progression-free survival (PFS) and response rate (RR). We evaluated functional germline polymorphisms involved in the EGFR- (EGF, EGFR), angiogenesis- (VEGF, IL-8, CXCR-2) - and drug- metabolism related genes (UGT1A1, MTHFR) for their potential role as molecular predictors for clinical outcome in pts treated with CB/IR vs. IR alone. Methods: DNA was extracted from all available formalin-fixed paraffin-embedded tumor samples from the phase III EPIC trial (US sites only). Genotyping was performed using PCR-RFLP assays and 5’ -end [g-33P] ATP’ labeled PCR-protocols. Results: 186 pts were treated either with IR/CB (arm A, 84 pts) or IR (arm B, 102 pts) only. In arm A, 11/84 pts (13%) showed CR or PR, whereas 73/84 (87%) pts had SD or PD. For arm B, 6/102 pts (6%) showed CR or PR, whereas 96/102 pts (94%) had SD or PD. Median PFS in arm A was 3.0 months (95%CI: 2.4- 4.1 months) vs 2.7 months (95%CI: 2.2–2.9 months) in arm B; median overall survival (OS) was 9.3 months (95%CI: 7.1–12.1 months) in arm A vs. 12.3 months (95%CI: 10.4- 17.9 months) in arm B. K-ras mutation status was not significantly associated with PFS or response to CB/IR in the subgroup of 186 patients. We found an EGFR-CA- repeat in intron 1 in arm A to be associated with PFS (p=0.031, log-rank test). In arm B, we found a significant association with RR (p=0.0103, Fisher's exact test) for MTHFR1298. Furthermore, MTHFR 677 (p =0.0048, log-rank test) and MTHFR 1298 (p=0.038, log-rank test) were also found to be associated with OS in arm B. In multivariate analysis, EGFR-CA-repeat was significantly associated with PFS (adjusted p= 0.023). Furthermore, MTHFR 677 and MTHFR 1298 was associated with OS (adjusted p=0.028 and 0.026, respectively, Cox-proportional hazards models), independent from K-ras mutation status, race and number of disease sites. Conclusions: Our study demonstrates the potential predictive value of polymorphisms in the EGFR- and MTHFR- gene in mCRC pts treated with IR+ CB. Further validation in additional clinical trials is necessary. [Table: see text]

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Impact of timing of antibiotic use on clinical outcomes in patients with urothelial cancer treated with immune checkpoint inhibitors (ICIs).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.5045 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 5045-5045

Author(s):

Chana Weinstock ◽

Pradeep Bandaru ◽

Laura L Fernandes ◽

Elaine Chang ◽

Andrew Girvin ◽

...

Keyword(s):

Urothelial Cancer ◽

Proportional Hazards ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Drug Approval ◽

Antibiotic Use ◽

Cox Proportional Hazards ◽

Exploratory Analysis ◽

Baseline Risk ◽

Study Results

5045 Background: Although recent evidence has suggested that patients who receive antibiotics (ABX) during the course of ICI treatment might decrease overall survival (OS) (1), our previous analysis did not support a difference in OS in urothelial cancer patients who did and did not use ABX during the course of ICI treatment without regard to timing (2). This updated analysis aims to addresses the question of timing; specifically, use of ABX in the 30-day window pre- or post- initiation of ICI treatment. Methods: We pooled data from 7 trials that led to drug approval and which included 1747 patients with advanced urothelial cancer treated with an ICI. Five trials enrolled patients who received prior platinum and 2 enrolled cisplatin-ineligible patients. Concomitant medication datasets were searched for systemic ABX use. The association between ABX use and survival was evaluated using Kaplan-Meier estimates and Cox proportional hazards regression models stratified by study. Results: Overall, 56% of patients were exposed to antibiotics (ABX+) and 43% were not exposed (ABX-). In an exploratory analysis, median OS was similar between arms: 9.7 vs. 9.3 months in ABX+ vs. ABX- patients, respectively (HR 0.96). However, OS results differed in the 27% of patients who were exposed to antibiotics in the 30-day window pre- or post- initiation of ICI treatment, for whom median OS was 4.7 months vs. 11.5 months in the ABX+ vs. ABX- patients, respectively (HR 1.8). This remained true after controlling for baseline risk prognostic factors (Bajorin and Bellmunt scores). Similar trends were observed for progression-free survival (PFS). Conclusions: Patients treated with ABX while on therapy with an ICI for urothelial cancer had similar OS outcomes to those not treated with ABX. However, in an exploratory analysis looking at ABX use in the 30-day window pre- or post-initiation of ICI treatment, OS appeared decreased in ABX+ vs ABX- patients. Our exploratory analyses appear to show an association of OS/PFS with timing of antibiotics. References: 1) Routy B, Science (2017) 2) Weinstock C, ASCO 2019, abstract. [Table: see text]

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A phase II open-label, single-center, nonrandomized trial of Y90-radioembolization in combination with nivolumab in Asian patients with advanced hepatocellular carcinoma: CA 209-678.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4590 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4590-4590

Author(s):

Wai Meng David Tai ◽

Kelvin Siu Hoong Loke ◽

Apoorva Gogna ◽

Sze Huey Tan ◽

David Chee Eng Ng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Checkpoint Inhibitors ◽

Progression Free Survival ◽

Liver Lesion ◽

Advanced Hepatocellular Carcinoma ◽

Open Label ◽

Significance Level ◽

Overall Response ◽

Asian Patients ◽

Y90 Radioembolization

4590 Background: Nivolumab (N) and Y90-radioembolization (RE) are both therapeutic options in advanced hepatocellular carcinoma (aHCC). Increasing evidence suggests that radiotherapy synergizes with immune checkpoint inhibitors to augment anti-tumour effects. Methods: Eligible Child-Pugh A aHCC patients (pts) were treated with Y90-RE followed by N 240mg, 21 days after Y90-RE and every 2 weeks thereafter. Pre- and on-treatment tumor biopsies together with circulating biomarkers were obtained. Primary end-point was overall response rate (ORR) (per RECIST v 1.1). Overall response was defined as the composite overall response observed for the lesions within Y90-RE field and outside Y90-RE field. Key secondary end points included disease control rate (DCR), progression free survival (PFS), overall survival (OS), and safety. 36 evaluable pts were needed to assess whether the addition of N improved the ORR of Y90-RE from 21% to 41% as determined by Simon two-stage optimal design with 80% power and one sided significance level of 0.05. Results: Forty pts were enrolled of which 36 were evaluable. At baseline: 63.9% were HepB in aetiology; 63.9% BCLC stage C; 47.2% had AFP > 400ng/mL; number of liver lesions – median 5 (range 1- 20); size of largest liver lesion – median 80mm (range 14-177mm); 27.8% had prior TACE; and 13.9% had prior systemic therapy. ORR was 31% (95% CI 16.4 - 48.1%). Eight out of 11 responders had not progressed at study cut-off. DCR was 58.3%. 81% of target lesions within Y90-RE field regressed. With a median follow up of 16.4 months, median PFS and OS were 4.6 months (95% CI 2.3m - 8.4m) and 15.1 months (95% CI 7.8m - NE) respectively. Six- and 12-month PFS rates were 44.2% (95% CI 27.3% - 59.9%) and 26.1% (95% CI 11.2% - 43.8%) respectively. Overall, N+ Y90-RE was well tolerated and safe; only 11% had grade 3/4 treatment related adverse events (AEs). Responders demonstrated significant alterations of LIF, MIG and Eotaxin3 levels in the pre-treatment cytokine analyses. Conclusions: Combination N+Y90-RE resulted in an encouraging ORR of 31% (95% CI 16.4 - 48.1%) in aHCC. 81% of target lesions within Y90-RE field regressed suggesting synergy in combining Y90-RE with nivolumab. This combination is safe and tolerable with low G3/4 treatment related AEs of 11%. Further biomarker analyses will be presented at the meeting. Clinical trial information: NCT03033446 .

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Transarterial Chemoembolization Improves Survival in Advanced Hepatocellular Carcinoma Patients Treated with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors

10.21203/rs.3.rs-679376/v1 ◽

2021 ◽

Author(s):

Yue Hu ◽

Tao Pan ◽

Xi Cai ◽

Quansheng He ◽

Yubao Zheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Tyrosine Kinase ◽

Immune Checkpoint ◽

Transarterial Chemoembolization ◽

Immune Checkpoint Inhibitors ◽

Kinase Inhibitors ◽

Checkpoint Inhibitors ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Hcc ◽

Tace Group

Abstract BackgroundThe survival benefit and safety of transarterial chemoembolization (TACE) for advanced Hepatocellular Carcinoma (HCC) patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) is unclear. We aimed to investigate the efficacy and safety of TACE combined with TKIs and ICIs the treatment of advanced HCC. MethodsIn this study, the conditions of 147 patients with advanced HCC who underwent TKIs plus ICIs treatment between July 2017 and April 2020 were evaluated. We divided these patients into the TACE group and non-TACE group based on whether they were treated with TACE during TKIs plus ICIs treatment, and compared their survival outcomes, especially overall survival (OS), and whether they were exposed to unexpected toxicities. ResultsIn this study, a total of 98 patients who underwent TACE during TKIs plus ICIs treatment were included in the TACE group, while the other 49 patients were included in the non-TACE group. According to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST), the objective response rate (ORR) of the TACE group was higher than that of the non-TACE group (ORR 74.5% vs. 40.8%, p ＜0.001). The OS of the TACE group was significantly longer than the non-TACE group (OS 19.3 months vs. 10.8 months, p = 0.010). The incidence of grade 3-4 toxicities in the TACE group was similar to that in the non-TACE group (33.7% vs. 28.6%, p = 0.532). ConclusionsThe TACE treatment combined with TKIs plus ICIs resulted in longer OS compared to the treatment of systemic TKIs plus ICIs without TACE during the process of advanced HCC.

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