Clinical impact of lenvatinib in patients with unresectable hepatocellular carcinoma who received sorafenib

Background Lenvatinib has been approved for use in the systemic treatment for unresectable hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy and safety of lenvatinib in patients with unresectable HCC who received sorafenib. Methods A total of 40 patients who received lenvatinib after sorafenib were retrospectively identified: as second line in 20 patients, third line in 10 patients, and fourth line and later lines in 10 patients. The treatment response to lenvatinib was determined in accordance with the guidelines of the modified Response Evaluation Criteria in Solid Tumors (mRECIST) every 2–3 months after commencement of lenvatinib. Results Median progression-free survival (PFS) and median overall survival (OS) of the whole population were 3.3 and 9.8 months, respectively. The objective response rate was 27.5%. Univariate and multivariate analyses showed that alpha-fetoprotein level >400 ng/mL was an independent prognostic factor of worse PFS and OS. The clinical outcomes of lenvatinib therapy as second-line, third-line, or fourth line and later line treatment were similar, and previous response to sorafenib could predict the response to subsequent lenvatinib. Most adverse events were grades 1–2, and the majority of patients tolerated the side effects. Our study confirms the efficacy and safety of lenvatinib as second-line and later line treatment for patients with unresectable HCC who received sorafenib in clinical practice.

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The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Patients with Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab

Cancers ◽

10.3390/cancers14020343 ◽

2022 ◽

Vol 14 (2) ◽

pp. 343

Author(s):

Jing-Houng Wang ◽

Yen-Yang Chen ◽

Kwong-Ming Kee ◽

Chih-Chi Wang ◽

Ming-Chao Tsai ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Objective Response ◽

Progression Free Survival ◽

Neutrophil To Lymphocyte Ratio ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Lymphocyte Ratio ◽

Third Line

Atezolizumab plus bevacizumab has been approved as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma (uHCC). This study was designed to assess the clinical impact of atezolizumab plus bevacizumab in uHCC patients. A total of 48 uHCC patients receiving atezolizumab plus bevacizumab were identified, including first-line, second-line, third-line, and later-line settings. In these patients, the median progression-free survival (PFS) was 5.0 months, including 5.0 months for the first-line treatment, not reached for the second-line treatment, and 2.5 months for the third line and later line treatment. The objective response rate and disease control rate to atezolizumab plus bevacizumab were 27.1% and 68.8%, respectively. The severity of most adverse events was predominantly grade 1–2, and most patients tolerated the toxicities. The ratios of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) were used to predict PFS in these patients. The optimal cutoff values of NLR and PLR were 3 and 230, and NLR and PLR were independent prognostic factors for superior PFS in the univariate and multivariate analyses. Our study confirms the efficacy and safety of atezolizumab plus bevacizumab in uHCC patients in clinical practice and demonstrates the prognostic role of NLR and PLR for PFS in these patients.

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Efficacy and Safety of Lenvatinib Therapy for Unresectable Hepatocellular Carcinoma in a Real-World Practice in Korea

Liver Cancer ◽

10.1159/000512239 ◽

2021 ◽

pp. 1-11

Author(s):

Myung Ji Goh ◽

Joo Hyun Oh ◽

Yewan Park ◽

Jihye Kim ◽

Wonseok Kang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Prognostic Factors ◽

Disease Progression ◽

Real World ◽

Medical Center ◽

Objective Response ◽

Progression Free Survival ◽

Efficacy And Safety ◽

Eligibility Criteria ◽

Unresectable Hepatocellular Carcinoma

Background: Lenvatinib has been recently approved as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Korea. We aimed to study the efficacy and safety of lenvatinib therapy in a real-world practice and to find prognostic factors related to survival and disease progression. Methods: A hospital-based retrospective study was conducted on 111 consecutive patients who had unresectable HCC and were treated with lenvatinib at Samsung Medical Center from October 2018 to March 2020. Efficacy was determined using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria in 111 patients who completed 1st tumor assessment. Safety was evaluated in 116 HCC patients including 5 patients who discontinued lenvatinib due to adverse events (AEs) before 1st tumor assessment using Common Terminology Criteria for AEs version 5.0. Results: A total of 111 patients with a median age of 59 years were analyzed during a median follow-up duration of 6.2 (4.4–9.0) months. The Kaplan-Meier estimate of overall survival was 10.5 months, and the median progression-free survival was 6.2 months. Based on mRECIST criteria, the objective response rate was 18.9% and disease control rate was 75.7%. AEs developed in 86/116 (74.1%) patients, and grade ≥3 AEs developed in 16/116 (13.8%) patients. Diarrhea, hand-foot skin rash, abdominal pain, hypertension, and anorexia were identified as the AEs with the highest frequencies of any grade. REFLECT eligibility criteria including tumor extent ≥50% liver occupation or inadequate bone marrow function and occurrence of anorexia were prognostic factors for survival, and occurrence of diarrhea was a favorable factor for disease progression. Conclusion: Lenvatinib therapy showed a favorable efficacy and safety in a real-world practice. The REFLECT eligibility criteria and specific AEs could be one of the prognostic markers.

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Efficacy of weekly paclitaxel-bevacizumab combination in advanced nonsquamous non-small cell lung cancer (NSCLC): AVATAX, a retrospective multicentric study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21086 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21086-e21086

Author(s):

Geoffroy Bilger ◽

Anne-Claire Toffart ◽

Marie Darasson ◽

Michaël Duruisseaux ◽

Lucie Ulmer ◽

...

Keyword(s):

Performance Status ◽

Objective Response ◽

Progression Free Survival ◽

Line Treatment ◽

Second Line ◽

Multicentric Study ◽

Significant Difference ◽

Third Line ◽

And Performance ◽

Line Setting

e21086 Background: With the growing role of immunotherapy (ICI) as first-line setting for advanced NSCLC, strategies must be redefined after failure. The combination paclitaxel-bevacizumab showed in the ULTIMATE trial a significant superiority versus docetaxel as second or third-line treatment. Limited restropective studies has demonstrated unexpected efficacy of chemotherapy after prior progression on ICI. This combination could be use as salvage treatment following ICI. Methods: This multi-centric retrospective study identifies patients treated with the combination paclitaxel-bevacizumab in metastatic non-squamous NSCLC as second-line therapy or beyond. Main objectives were to describe safety and efficacy of this combination, with a special attention to the sub-group treated just after ICI. Results: From January 2010 to February 2020, 314 patients started the paclitaxel-bevacizumab combination : 55% male, with a median age of 60 years, 27% with a performance status ≥2, 45% with brain metastases. A majority of patients were treated in second (20%) and third-line (39%), and 28% were treated just after ICI failure (88/314). Objective response rate (ORR) was 40% and disease control rate was 77 %. Median progression-free survival (PFS) and overall survival (OS) were 5,7 months [IQ,3,2–9,6] and 10,8 months [IQ,5,3–19,6] respectively. All grades adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued a monotherapy alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compare to those not previously treated with ICI (ICI-) : 7,0 months [IQ,4,2–11,0] vs 5,2 months [IQ,2,9–8,8] p (log-rank) = 0,01. There was not statistically significant difference in term of OS between this two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment (ICI+) and performance status. Conclusions: This study confirms an acceptable toxicity profile associated with interesting efficacy of the combination paclitaxel-bevacizumab as second-line treatment or beyond for non–squamous NSCLC patients, particularly after progression with ICI.

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Efficacy and safety of lenvatinib in the real-world treatment of hepatocellular carcinoma: Results from a Canadian multicenter database (HCC CHORD).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.275 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 275-275

Author(s):

Carla Pires Amaro ◽

Michael J Allen ◽

Jennifer J. Knox ◽

Erica S Tsang ◽

Howard John Lim ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Real World ◽

Objective Response ◽

Progression Free Survival ◽

Drug Discontinuation ◽

Line Treatment ◽

Efficacy And Safety ◽

First Line ◽

The Real ◽

First Line Therapy

275 Background: The REFLECT trial establishedlenvatinib (LEN) as a first-line treatment option for hepatocellular carcinoma (HCC). Compared to sorafenib (S), LEN has a higher objective response rate (ORR) and progression-free survival (PFS) with a slightly different toxicity profile. The aim of this study was to gather data regarding the efficacy and safety of LEN when used in the real-world treatment of HCC. To our knowledge, this is the first study to examine LEN use in HCC patients treated outside of Asia. Methods: HCC patients treated with LEN from 10 cancer centers in the Canadian provinces of British Columbia, Alberta, Ontario and Nova Scotia between July 2018 to July 2020 were included. Overall survival (OS), PFS, disease control rate (DCR) and ORR were retrospectively analyzed and compared across first- and second-to-fourth line use of LEN. ORR was determined radiographically according to the treating physician´s opinion in clinical notes and not RECIST 1.1 or mRECIST. Toxicities were also examined. Results: A total of 220 patients were included in this analysis. Median age was 67 years, 80% were men and 25.5% East Asian. The most frequent causes of liver disease were hepatitis C (37%) and B (26%). 62% of patients received any localized treatment before LEN, of those 26% had TACE, 15% TARE and 7.7% had liver transplant. Before starting LEN 29% of patients were ECOG 0 and 59% were ECOG 1. Most patients were Child-Pugh A (81%) and BCLC stage C (75.5%). Main portal vein invasion was present in 14% of the patients. Median follow-up was 4.5 months. A total of 173 patients (79%) received LEN as first line therapy and 47 patients (21%) were treated in second-to-fourth line. Of patients receiving LEN in first line, 22 (13%) started treatment with S, but switched to LEN before progression due to poor tolerance of S. ORR, DCR, PFS and OS are shown in the table. Toxicities occurred in 86% of patients and led to dose reductions in 76 (35%) patients and drug discontinuation in 53 (24%) patients. The most common side effects were fatigue (59%), hypertension (41%), decreased appetite (25%) and diarrhea (22%). Conclusions: Outcomes of HCC patients treated in Canada with LEN in the first line are comparable to those demonstrated in the REFLECT trial, despite the inclusion of Child-Pugh B and ECOG >1 patients. LEN use in second or later lines also showed similar outcomes, although more conclusions are difficult to draw due to the small numbers. LEN appears to be effective and safe in real world practice outside of Asia in first- and second-to-fourth line treatment of HCC. [Table: see text]

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Activity of new agents (NAs) as third-line treatment in metastatic castration-resistant prostate cancer (mCRPC) patients (pts) showing a primary resistance (PRes) to NAs-based second line therapy after docetaxel (DOC): Preliminary results from a multicenter Italian study.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.216 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 216-216

Author(s):

Orazio Caffo ◽

Ugo De Giorgi ◽

Gaetano Facchini ◽

Lucia Fratino ◽

Donatello Gasparro ◽

...

Keyword(s):

Clinical Outcomes ◽

Objective Response ◽

Progression Free Survival ◽

Consecutive Series ◽

Line Treatment ◽

Second Line ◽

Castration Resistant Prostate Cancer ◽

Primary Resistance ◽

Third Line ◽

Third Line Treatment

216 Background: The androgen receptor machinery remains the ultimate target of NAs in mCRPC post-DOC, abiraterone acetate (AA), cabazitaxel (CAB), and enzalutamide (ENZ). It is postulated that some mechanisms of resistance may be common to all NAs. This may be crucial in planning their sequential use, mainly when a PRes to one of them is observed. The present study assessed the activity of NAs in pts who previously experienced a PRes to another NA administered after DOC. Methods: We collected data of pts who received sequentially two NAs after DOC in 32 Italian hospital. For each pt we recorded the clinical outcomes of all treatments received after DOC. For the study purpose, we consider with PRes all pts progressing within 3 months after second line NA start. All other pts were considered as without PRes. Results: A consecutive series of 271 mCRPC pts, median age 71 yrs (46-91), with bone (89%), nodal (56%) or visceral (19%) mets, was collected. All pts received NAs as second line after DOC (AA 54% – CAB 34%– ENZ 12%) and 54 (20%) showed a PRes. Among these, third line treatment [AA (31%), CAB (42%), and ENZ (27%)], produced a biochemical and an objective response rate of 11% in both cases, with a median progression free survival (PFS) and a median overall survival (OS) of 4 mos and 8 mos, respectively. No statistically significant differences were observed in terms of clinical outcomes on the basis of NA sequences (see Table). Conclusions: It appears from this preliminary data, that the activity of NAs in pts showing a PRes to second line NAs is very limited, regardless the NA is administered. [Table: see text]

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Efficacy and safety of regorafenib in combination with chemotherapy as second-line therapy in patients with metastatic colorectal cancer: A network meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.115 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 115-115

Author(s):

Xiaoyu Xie ◽

Jianwei Zhang ◽

Huabin Hu ◽

Yue Cai ◽

Zehua Wu ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Meta Analysis ◽

Objective Response ◽

Progression Free Survival ◽

Biological Agents ◽

Line Treatment ◽

Second Line ◽

Efficacy And Safety ◽

R Software

115 Background: Recent studies have shown efficacy of chemotherapy (CTX) in combination with different biological agents including regorafenib (REG) in second-line treatment of metastatic colorectal cancer (mCRC). As there is no evidence on the relative efficacy and safety of REG as compared to other biological agents in combination with CTX, we evaluated the same in this network meta-analysis (NMA). Methods: Randomized controlled trials (RCTs) comparing efficacy and safety of biological agents + CTX against CTX alone as second-line treatment of mCRC were retrieved from PubMed, EMBASE and Cochrane databases. Progression free survival (PFS) was the primary outcome, while objective response rate (ORR), overall survival (OS) and safety were secondary outcomes. Outcomes were compared by random/mixed-effects NMA using Bayesian (R software, Gemtc package) and frequentist (R software, netmeta package) approaches. Results: Twelve RCTs comparing 9 different treatment regimens with a total of 6805 patients were included for analysis. Hazard ratios (HR)/ odds ratio (OR)/ relative risk (RR) and 95% confidence intervals (CI) for PFS, ORR and grade> 3 adverse events (AE) of selected comparisons from the results of the NMA are shown in table. Conclusions: REG combined with CTX might be a potential alternative to conventional therapeutic options and could be considered as the best option for treating KRAS and BRAF mutated mCRC patients. Future RCTs are needed to confirm our results. [Table: see text]

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HX008, an anti-PD1 antibody, plus irinotecan as second-line treatment for advanced gastric or gastroesophageal junction cancer: a multicenter, single-arm phase II trial

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001279 ◽

2020 ◽

Vol 8 (2) ◽

pp. e001279

Author(s):

Yan Song ◽

Ning Li ◽

Qun Li ◽

Xinjun Liang ◽

Shu Zhang ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Trial ◽

Gastroesophageal Junction ◽

Objective Response ◽

Evaluation Criteria ◽

Progression Free Survival ◽

Line Treatment ◽

Second Line ◽

Open Label ◽

Gastroesophageal Junction Cancer

BackgroundIrinotecan is used as second-line treatment in advanced gastric or gastroesophageal junction (G/GEJ) cancer. The role of anti-programmed death-1 (PD-1) antibody plus irinotecan, in this setting and population is unclear.MethodsThis multicenter, open-label, single-arm, phase II trial was conducted in 11 Chinese hospitals. Eligible patients had histologically confirmed advanced G/GEJ cancer that refractory to, or intolerant of, first-line chemotherapy with a platinum and/or fluoropyrimidine. Subjects received HX008 200 mg intravenously every 3 weeks plus irinotecan 160 mg/m2 intravenously every 2 weeks until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) as assessed according to Response Evaluation Criteria In Solid Tumors V.1.1.ResultsBetween October 2018 and September 2019, a total of 58 patients with advanced G/GEJ cancer were enrolled in this study. Median follow-up was 10.5 months (range 7.4–18.9) months. Confirmed ORR was observed in 16 patients, for an ORR of 27.6% (95% CI 16.1% to 39.1%); 19 patients experienced stable disease, leading to a disease control rate of 60.3% (95% CI 46.4% to 73.0%). ORR in patients with PD-ligand 1 (L1) positive (Combined Positive Score (CPS) ≥1) and negative (CPS＜1) tumors was 38.5% (5/13) and 37.5% (3/8), respectively. Median duration of response was 8.0 months (range 1.5–12.5), 6 of 16 (37.5%) responses were ongoing. Median progression-free survival (PFS) was 4.2 months (95% CI 2.2 to 5.5). Median overall survival (OS) was not reached (NR) (95% CI 8.7 to NR). Patients with PD-L1 positive tumors tended to have longer OS than those with PD-L1 negative tumors, but the difference was not statistically significant (NR vs 8.7 months, p=0.1858).The most common treatment-related adverse events of grade 3 or 4 included neutropenia (32.8%), leukopenia (31.0%), anemia (17.2%), decreased appetite (8.6%), vomit (6.9%), nausea (6.9%) and fatigue (5.2%). There were no treatment-related deaths.ConclusionThe combination of HX008 and irinotecan demonstrated promising activity and manageable safety as second-line treatment in patients with advanced G/GEJ cancer, which warrants further study.Trial registration numberNCT03704246

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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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REFLECT—a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset

Journal of Gastroenterology ◽

10.1007/s00535-019-01642-1 ◽

2019 ◽

Vol 55 (1) ◽

pp. 113-122 ◽

Cited By ~ 14

Author(s):

Tatsuya Yamashita ◽

Masatoshi Kudo ◽

Kenji Ikeda ◽

Namiki Izumi ◽

Ryosuke Tateishi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Adverse Events ◽

Japanese Population ◽

Objective Response ◽

Dose Intensity ◽

Progression Free Survival ◽

Japanese Patients ◽

Efficacy And Safety ◽

Phase 3 ◽

Unresectable Hepatocellular Carcinoma

Abstract Background A phase 3, multinational, randomized, non-inferiority trial (REFLECT) compared the efficacy and safety of lenvatinib (LEN) and sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (uHCC). LEN had an effect on overall survival (OS) compared to SOR, statistically confirmed by non-inferiority [OS: median = 13.6 months vs. 12.3 months; hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.79–1.06], and demonstrated statistically significant improvements in progression-free survival (PFS) and the objective response rate (ORR) in the overall population. The results of a subset analysis that evaluated the efficacy and safety of LEN and SOR in the Japanese population are reported. Methods The intent-to-treat population enrolled in Japan was analyzed. Results Of 954 patients in the overall population, 168 Japanese patients were assigned to the LEN arm (N = 81) or the SOR arm (N = 87). Median OS was 17.6 months for LEN vs. 17.8 months for SOR (HR 0.90; 95% CI 0.62–1.29). LEN showed statistically significant improvements over SOR in PFS (7.2 months vs. 4.6 months) and ORR (29.6% vs. 6.9%). The relative dose intensity of LEN and SOR in the Japanese population was lower than in the overall population. Frequently observed, related adverse events included palmar-plantar erythrodysaesthesia syndrome (PPES), hypertension, decreased appetite, and proteinuria in the LEN arm, and PPES, hypertension, diarrhea, and alopecia in the SOR arm. Conclusions The efficacy and safety of LEN in the Japanese population were similar to those in the overall population of REFLECT. With manageable adverse events, LEN is a new treatment option for Japanese patients with uHCC. Trial registration ID ClinicalTrials.gov. No. NCT01761266.

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Early Experience of Ramucirumab Therapy in Japanese Patients With Unresectable Hepatocellular Carcinoma in Real-World Practice

10.21203/rs.3.rs-111378/v1 ◽

2020 ◽

Author(s):

Yuka Hayakawa ◽

Kaoru Tsuchiya ◽

Masayuki Kurosaki ◽

Yutaka Yasui ◽

Shun Kaneko ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Renal Function ◽

Real World ◽

Objective Response ◽

Evaluation Criteria ◽

Japanese Patients ◽

Drug Discontinuation ◽

Unresectable Hepatocellular Carcinoma ◽

Modified Recist ◽

Third Line

Abstract BackgroundWe aimed to investigate the efficacy and safety of ramucirumab therapy in Japanese patients with unresectable hepatocellular carcinoma (u-HCC) in real-world practice.MethodsA total of 16 patients with u-HCC were treated with ramucirumab of ≥2 cycles between July 2019 and April 2020. Modified response evaluation criteria in solid tumors (RECIST) and RECIST version 1.1 were used to evaluate radiological responses.ResultsThe patients received ramucirumab as second-line (n = 4), third-line (n = 2), and fourth-line (n = 10). Median observation period was 3.7 months and 3 patients treated as fourth-line died from HCC progression. According to modified RECIST, the objective response rate (ORR) and disease control rate (DCR) were 27.2% and 81.8%, respectively. ORR and DCR by RECIST version 1.1 were 9.1 % and 72.7%, respectively. PFS at 3 months was 68.2%. Drug discontinuation caused by adverse events (AEs) was reported in 7 patients treated as fourth-line and 1 patient as third-line. Pretreatment creatinine (Cr) and estimated glomerular filtration rate (eGFR) were significantly higher in patients with discontinuation owing to AEs (P = 0.01 and P = 0.02). Urine protein-to-creatine ratio after 4 weeks was significantly higher in patients with impaired renal function than patients with preserved renal function (0.93 vs. 0.14; P = 0.017).ConclusionRamucirumab therapy was found to have similar radiological responses between u-HCC patients with single and multiple experiences of TKI therapies. The pretreatment factors would be associated with the incidence of AEs during the therapy.

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