Organ Specific Responses to First-line Lenvatinib Plus Anti-PD-1 Antibodies in Patients With Unresectable Hepatocellular Carcinoma: a Retrospective Analysis

Abstract BackgroundWe evaluated organ-specific response rates (OSRRs) to first-line lenvatinib plus anti-PD-1 antibodies in patients with advanced hepatocellular carcinoma (HCC).MethodsThis retrospective analysis included Chinese patients with unresectable/advanced HCC who received first-line lenvatinib (8 mg/day) plus ≥3 infusions of anti-PD-1 antibodies between October 2018 and May 2020. Tumor and macrovascular tumor thrombi (MVTT) treatment responses were evaluated every 2 months using RECIST v1.1. The overall response rate (ORR)/OSRR was defined as the percentage of patients with a best overall response of complete or partial response (CR or PR).ResultsIn total, 60 patients were included in the analysis; 96.7% had measurable intrahepatic lesions, 55% had MVTT and 26.7% had extrahepatic disease. In all 60 patients, the ORR was 33.3%, median progression-free survival was 7.0 months (95% CI, 1.7-12.3) and median overall survival was not reached. The OSRR for MVTT (54.5%) was higher versus intrahepatic tumors (32.8%), extrahepatic lung metastases (37.5%) and lymph node metastases (33.3%). Among 33 patients with intrahepatic tumors and MVTT, 18 had differential responses in each site, including 13 with a better response in MVTT versus intrahepatic lesions. Among 18 patients whose MVTT achieved a radiographic CR or PR, six underwent surgical resection: 4/6 achieved a pathological CR in MVTT and 2/6 in the intrahepatic tumor.ConclusionsFirst-line lenvatinib plus anti-PD-1 antibodies resulted in better tumor responses in MVTT versus intrahepatic lesions. Complete MVTT necrosis may allow downstaging and subsequent eligibility for surgical resection in a proportion of patients with advanced HCC.

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Organ specific responses to first-line lenvatinib plus anti-PD-1 antibodies in patients with unresectable hepatocellular carcinoma: a retrospective analysis

Biomarker Research ◽

10.1186/s40364-021-00274-z ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Cheng Huang ◽

Xiao-Dong Zhu ◽

Ying-Hao Shen ◽

Dong Wu ◽

Yuan Ji ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Retrospective Analysis ◽

Surgical Resection ◽

Chinese Patients ◽

Specific Response ◽

Advanced Hepatocellular Carcinoma ◽

First Line ◽

Advanced Hcc ◽

Overall Response ◽

Organ Specific

Abstract Background We evaluated organ-specific response rates (OSRRs) to first-line lenvatinib plus anti-PD-1 antibodies in patients with advanced hepatocellular carcinoma (HCC). Methods This retrospective analysis included Chinese patients with unresectable/advanced HCC who received first-line lenvatinib (8 mg/day) plus ≥3 infusions of anti-PD-1 antibodies between October 2018 and May 2020. Tumor and macrovascular tumor thrombi (MVTT) treatment responses were evaluated every 2 months using RECIST v1.1. The overall response rate (ORR)/OSRR was defined as the percentage of patients with a best overall response of complete or partial response (CR or PR). Results In total, 60 patients were included in the analysis; 96.7% had measurable intrahepatic lesions, 55% had MVTT and 26.7% had extrahepatic disease. In all 60 patients, the ORR was 33.3%, median progression-free survival was 7.0 months (95% CI, 1.7–12.3) and median overall survival was not reached. The OSRR for MVTT (54.5%) was higher versus intrahepatic tumors (32.8%), extrahepatic lung metastases (37.5%) and lymph node metastases (33.3%). Among 33 patients with intrahepatic tumors and MVTT, 18 had differential responses in each site, including 13 with a better response in MVTT versus intrahepatic lesions. Among 18 patients whose MVTT achieved a radiographic CR or PR, six underwent surgical resection: 4/6 achieved a pathological CR in MVTT and 2/6 in the intrahepatic tumor. Conclusions First-line lenvatinib plus anti-PD-1 antibodies resulted in better tumor responses in MVTT versus intrahepatic lesions. Complete MVTT necrosis may allow downstaging and subsequent eligibility for surgical resection in a proportion of patients with advanced HCC.

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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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Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

Medicina ◽

10.3390/medicina55100707 ◽

2019 ◽

Vol 55 (10) ◽

pp. 707 ◽

Cited By ~ 12

Author(s):

Oronzo Brunetti ◽

Antonio Gnoni ◽

Antonella Licchetta ◽

Vito Longo ◽

Angela Calabrese ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Factors ◽

Prognostic Markers ◽

Kinase Inhibitor ◽

Quality Standard ◽

Advanced Hepatocellular Carcinoma ◽

Line Treatment ◽

First Line ◽

Advanced Hcc ◽

First Line Treatment

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

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Evolution of Survival Impact of Molecular Target Agents in Patients with Advanced Hepatocellular Carcinoma

Liver Cancer ◽

10.1159/000519868 ◽

2021 ◽

pp. 1-13

Author(s):

Kazufumi Kobayashi ◽

Sadahisa Ogasawara ◽

Aya Takahashi ◽

Yuya Seko ◽

Hidemi Unozawa ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Treatment Duration ◽

Molecular Target ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Stage ◽

First Line ◽

Advanced Hcc ◽

Period 2 ◽

Study Population ◽

The Impact

Background and Aims: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is expected to improve as multiple molecular target agents (MTAs) are now available. However, the impact of the availability of sequential MTAs has not been fully verified yet. Approach and Results: We retrospectively collected the data on the whole clinical course of 877 patients who received any MTAs as first-line systemic therapy for advanced HCC between June 2009 and March 2019. The study population was divided into 3 groups according to the date of first-line MTA administration (period 1: 2009–2012, n = 267; period 2: 2013–2016, n = 352; period 3: 2017–2019, n = 258). Then, we compared the number of MTAs used, overall survival (OS), and MTA treatment duration among the 3 groups. Analysis was also performed separately for advanced-stage and nonadvanced-stage HCC. The proportion of patients who received multiple MTAs was remarkably increased over time (1.1%, 10.2%, and 42.6% in periods 1, 2, and 3, respectively, p < 0.001). The median OS times were prolonged to 10.4, 11.3, and 15.2 months in periods 1, 2, and 3, respectively (p = 0.016). Similarly, the MTA treatment durations were extended (2.7, 3.2, and 6.6 months in periods 1, 2, and 3, respectively; p < 0.001). We confirmed that the correlation between OS and MTA treatment duration was strengthened (period 1: 0.395, period 2: 0.505, and period 3: 0.667). All these trends were pronounced in the patients with advanced-stage HCC but limited in the patients with nonadvanced-stage HCC. Conclusions: The availability of multiple MTAs had steadily improved the prognosis of patients with advanced HCC patients, particularly advanced-stage HCC patients.

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Final phase Ib data for the oral c-Met inhibitor tepotinib in patients with previously treated advanced hepatocellular carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15676 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15676-e15676 ◽

Cited By ~ 1

Author(s):

Sandrine J. Faivre ◽

Jean-Frédéric Blanc ◽

Philippe Merle ◽

Angelica Fasolo ◽

Angelo Iacobellis ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase Ii ◽

Tumor Size ◽

Advanced Hepatocellular Carcinoma ◽

First Line ◽

Phase Ib ◽

Advanced Hcc ◽

Peripheral Edema ◽

Met Inhibitor ◽

Grade 3

e15676 Background: The prognosis for patients (pts) with advanced hepatocellular carcinoma (HCC) after failure of sorafenib is poor, with few systemic therapy options. c-Met is a receptor tyrosine kinase implicated in the progression of HCC. Tepotinib, a highly selective c-Met inhibitor, has shown activity first-line in patients with c-Met+ HCC. We report final results of a phase Ib study of tepotinib in pts with advanced HCC after failure of first-line sorafenib. Methods: Eligible pts were ≥18 years with advanced HCC, Child-Pugh Class A, ECOG PS 0-1, and progression after ≥4 weeks of sorafenib. Tepotinib doses of 300 and 500 mg/day on a 21-day cycle were explored to establish the recommended phase II dose (RP2D) of tepotinib. Secondary objectives included antitumor activity by RECIST v1.1, biochemical response, and safety. Results: Seventeen pts were enrolled: 4 pts received tepotinib 300 mg/day and 13 pts 500 mg/day, confirmed as the RP2D. Fourteen pts experienced treatment-related adverse events (TRAEs), the most frequent being peripheral edema (n = 5, 2 grade 3), lipase increase (2, 1 grade 3), acute kidney injury (2, 1 grade 3), renal impairment (2, 1 grade 3), fatigue (2), nausea (2), asthenia (2). One pt with peripheral edema permanently discontinued treatment. No grade ≥4 TRAEs and no dose-limiting toxicities (DLTs) were reported. The best overall response was partial response (PR) in 2 pts and stable disease (SD) in 4 pts. The duration of the PRs was 57 and 91 weeks. In the first of these pts, tumor size decreased by 55% and serum alfa-fetoprotein (AFP) levels had decreased from 15,923 μg/L at baseline to < 3,000 μg/L by day 15 of cycle 2 and remained at this level until progression. In the second pt, tumor size decreased by > 60% from baseline. No consistent change in AFP was seen in pts with SD. Median overall survival was 7.2 months (range 0.7–22.9 months). Conclusions: The RP2D of tepotinib as second-line therapy for pts with advanced HCC who progress after sorafenib treatment is 500 mg/day. Tepotinib was well tolerated at this dose and showed signs of activity. The ongoing phase II part of this trial is investigating the efficacy and safety of tepotinib 500 mg/day in pts with c-Met+ HCC. Clinical trial information: NCT02115373.

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Donafenib Versus Sorafenib in First-Line Treatment of Unresectable or Metastatic Hepatocellular Carcinoma: A Randomized, Open-Label, Parallel-Controlled Phase II-III Trial

Journal of Clinical Oncology ◽

10.1200/jco.21.00163 ◽

2021 ◽

pp. JCO.21.00163

Author(s):

Shukui Qin ◽

Feng Bi ◽

Shanzhi Gu ◽

Yuxian Bai ◽

Zhendong Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase Ii ◽

Objective Response ◽

Chinese Patients ◽

First Line ◽

Open Label ◽

Multikinase Inhibitor ◽

Sorafenib Treatment ◽

Advanced Hcc ◽

Intention To Treat

PURPOSE Donafenib, a novel multikinase inhibitor and a deuterated sorafenib derivative, has shown efficacy in phase Ia and Ib hepatocellular carcinoma (HCC) studies. This study compared the efficacy and safety of donafenib versus sorafenib as first-line therapy for advanced HCC. PATIENTS AND METHODS This open-label, randomized, parallel-controlled, multicenter phase II-III trial enrolled patients with unresectable or metastatic HCC, a Child-Pugh score ≤ 7, and no prior systemic therapy from 37 sites across China. Patients were randomly assigned (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary end point was overall survival (OS), tested for noninferiority and superiority. Efficacy was primarily assessed in the full analysis set (FAS), and safety was assessed in all treated patients. RESULTS Between March 21, 2016, and April 16, 2018, 668 patients (intention-to-treat) were randomly assigned to donafenib and sorafenib treatment arms; the FAS included 328 and 331 patients, respectively. Median OS was significantly longer with donafenib than sorafenib treatment (FAS; 12.1 v 10.3 months; hazard ratio, 0.831; 95% CI, 0.699 to 0.988; P = .0245); donafenib also exhibited superior OS outcomes versus sorafenib in the intention-to-treat population. The median progression-free survival was 3.7 v 3.6 months ( P = .0570). The objective response rate was 4.6% v 2.7% ( P = .2448), and the disease control rate was 30.8% v 28.7% (FAS; P = .5532). Drug-related grade ≥ 3 adverse events occurred in significantly fewer patients receiving donafenib than sorafenib (125 [38%] v 165 [50%]; P = .0018). CONCLUSION Donafenib showed superiority over sorafenib in improving OS and has favorable safety and tolerability in Chinese patients with advanced HCC, showing promise as a potential first-line monotherapy for these patients.

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Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

10.20944/preprints201909.0071.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

Oronzo Brunetti ◽

Antonio Gnoni ◽

Antonella Licchetta ◽

Vito Longo ◽

Angela Calabrese ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Factors ◽

Prognostic Markers ◽

Kinase Inhibitor ◽

Quality Standard ◽

Advanced Hepatocellular Carcinoma ◽

Line Treatment ◽

First Line ◽

Advanced Hcc ◽

First Line Treatment

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, currently predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

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Clinical outcomes with multikinase inhibitors after progression on first-line atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma: A multinational, multicenter retrospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.272 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 272-272

Author(s):

Changhoon Yoo ◽

Jwa Hoon Kim ◽

Min-Hee Ryu ◽

Sook Ryun Park ◽

Joycelyn Jie Xin Lee ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Retrospective Study ◽

Disease Progression ◽

Clinical Outcomes ◽

Advanced Hepatocellular Carcinoma ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Advanced Hcc ◽

Multikinase Inhibitors

272 Background: Atezolizumab-bevacizumab is the new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, the optimal sequence of therapy after disease progression on atezolizumab-bevacizumab is unclear. Methods: This multinational, multicenter, retrospective study assessed clinical outcomes of patients with advanced HCC who received subsequent systemic therapy after progression on atezolizumab-bevacizumab in Korea, Hong Kong and Singapore between July 2016 and April 2019. Results: A total of 49 patients were included; the median age was 60 years (range, 3780) and 73.5% were male. All patients were classified as Child-Pugh A and Barcelona-Clinic Liver Cancer stage C. Multikinase inhibitors (MKIs), including sorafenib (n = 29), lenvatinib (n = 19), and cabozantinib (n = 1), were used as second-line therapy for all patients. The objective response rate (ORR) and disease control rate (DCR) were 6.1% and 63.3%, respectively, in all patients. With a median follow-up duration of 11.0 months, median progression-free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI] 1.84.9) and 14.7 months (95% CI 8.121.2) in all patients. Median PFS with lenvatinib was significantly longer than that with sorafenib (6.1 months vs. 2.5 months; P= 0.004), although there was no significant difference in median OS (16.6 months vs. 11.2 months; P= 0.347). Treatment-related adverse events (TRAEs) of any grade and grade 3 occurred in 42 (85.7%) and 8 (16.3%) of patients. Common TRAEs included hand-foot syndrome (HFS) (n = 26, 53.1%), fatigue (n = 14, 28.6%), hypertension (n = 14, 28.6%), and diarrhea (n = 12, 24.5%). Conclusions: Second-line treatment with MKIs, mostly sorafenib and lenvatinib, showed comparable efficacy and manageable toxicities in patients with advanced HCC after disease progression on atezolizumab-bevacizumab.

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Hybrid capture-based genomic profiling of circulating tumor DNA from patients with advanced hepatocellular carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15606 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15606-e15606

Author(s):

Mao Li ◽

Ailin Wei ◽

Wenzhuan Xie ◽

Jing Zhao ◽

Zhengyi Zhao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Circulating Tumor Dna ◽

Chinese Patients ◽

Advanced Hepatocellular Carcinoma ◽

Genomic Profiling ◽

Promising Alternative ◽

Hybrid Capture ◽

Advanced Hcc ◽

Tissue Biopsy ◽

Tumor Dna

e15606 Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies with a particularly high prevalence in China. The genomic profiling in HCC had been widely explored with tissue biopsy, however, given the intrinsic risks of invasive approach, blood-based circulating tumor DNA (ctDNA) has been proposed as a promising alternative. In this study, we aim to investigate whether the ctDNA may serve as a reliable tool to provide a more accurate molecular snapshot of HCC in Chinese patients. Methods: Plasma samples from 385 Chinese patients with advanced HCC were assayed for somatic genomic alternations by hybrid capture-based next-generation sequencing (NGS) with 150 genes and a mean sequencing depth of more than 3000×. The results were compared with our internal tissue genomic database of Chinese HCC patients (N = 873) tested by NGS and TCGA database (N = 373) tested by whole exome sequencing. Genomic alterations including single nucleotide variation (SNV), insertions/deletions, copy number variations, gene rearrangement and fusions were assessed. Results: Among 385 patients with ctDNA testing, somatic genomic alternations were detected in 97% of the patients (median = 5 alterations/patient). The most prevalent SNV mutations from ctDNA sequencing were TP53 (45.7%), TERT (19.5%), CTNNB1 (12.5%), and LRP1B (8.3%) compared to our tissue database (TP53 (61.2%), CTNNB1 (15.6%), TERT (13.3%), and LRP1B (11.0%)). While in TCGA database, the most common SNV mutations were found in TP53 (30.1%), CTNNB1 (26.0%), LRP1B (8.8%), ARID1A (8.6%), and SPTA1 (7.5%). Moreover, the level of MSAF was associated with detectable variant types, evidenced by a significant higher MSAF level observed when amplifications (P < 0.0001) or fusions (P = 0.008) were detected in the samples. Conclusions: Molecular analysis of patients with advanced HCC through ctDNA can serve as a reliable alternative to tissue biopsy. Chinese HCC patients may have different mutational landscapes to Western population. The utility of ctDNA analysis can provide therapeutically exploitable genomic profiles to identify potentially actionable gene alterations for targeted therapies.

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Apatinib as second-line therapy in Chinese patients with advanced hepatocellular carcinoma: A randomized, placebo-controlled, double-blind, phase III study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4507 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4507-4507 ◽

Cited By ~ 4

Author(s):

Qiu Li ◽

Shukui Qin ◽

Shanzhi Gu ◽

Xiaoming Chen ◽

Lizhu Lin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Hazard Ratio ◽

Phase Iii ◽

Chinese Patients ◽

Biological Behavior ◽

Advanced Hepatocellular Carcinoma ◽

Double Blind ◽

Sorafenib Treatment ◽

Advanced Hcc

4507 Background: Chinese patients (pts) account for more than 50% of hepatocellular carcinoma (HCC) cases in the world and have special features in etiology, biological behavior, treatment strategy and prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib, an inhibitor targeting vascular endothelial growth factor receptor-2, in Chinese pts with pretreated advanced HCC. Methods: In this randomized, placebo-controlled, double-blind, phase 3 trial done in 31 sites in China, pts with HCC who had received at least one line of systemic therapy (including sorafenib and oxaliplatin-based chemotherapy, which is another first-line standard-of-care in China) and had Child-Pugh liver function class A or B ≤7 points were enrolled. The pts were randomly assigned (2:1) to receive 750 mg apatinib orally once daily or placebo and stratified by ECOG performance status (0 or 1), previous sorafenib treatment (yes or no), and extrahepatic spread and/or macrovascular invasion (yes or no) in 28-day treatment cycles. The primary endpoint was overall survival (OS). Results: Between Apr 01, 2014 and May 03, 2017, 393 pts were randomized and received at least one dose of study treatment (261 in apatinib arm and 132 in placebo arm). The median OS was significantly longer with apatinib than that with placebo (8.7 months [95% CI 7.5-9.8] vs 6.8 months [95% CI 5.7-9.1]; hazard ratio 0.785 [95% CI 0.617-0.998]; p=0.0476). Pts in the apatinib arm also had prolonged median progression free survival (PFS) compared with those in the placebo arm (4.5 months [95% CI 3.9-4.7] vs 1.9 months [95% CI 1.9-2.0]; hazard ratio 0.471 [95% CI 0.369-0.601]; p˂0.0001). The objective response rate was 10.7% (95% CI 7.2-15.1) with apatinib versus 1.5% (95% CI 0.2-5.4) with placebo. Treatment-related adverse events (TRAEs) were reported in 250 (97.3%) pts in the apatinib arm and 92 (70.8%) pts in the placebo arm. The most common TRAEs of grade 3 and 4 were hypertension (71 [27.6%] pts in the apatinib arm vs 3 [2.3%] pts in the placebo arm), hand-foot syndrome (46 [17.9%] vs 0), decreased platelet count (34 [13.2%] vs 1 [0.8%]), and decreased neutrophil count (27 [10.5%] vs 0). 24 (9.3%) pts with apatinib and 13 (10.0%) pts with placebo died due to adverse events, and none were deemed treatment-related by investigators. Conclusions: Apatinib significantly prolonged OS and PFS in Chinese pts with pretreated advanced HCC, and was well tolerated with a manageable safety profile. Clinical trial information: NCT02329860 .

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