KEYNOTE-224: Phase II study of pembrolizumab in patients with previously treated advanced hepatocellular carcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS504-TPS504 ◽  
Author(s):  
Andrew X. Zhu ◽  
Jennifer J. Knox ◽  
Masatoshi Kudo ◽  
Stephen L. Chan ◽  
Richard S. Finn ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Ecog Performance Status ◽  
Previously Treated

TPS504 Background: The tyrosine kinase inhibitor sorafenib is the standard of care for first-line hepatocellular carcinoma (HCC). For patients with HCC after disease progression on sorafenib or for those with intolerance to sorafenib, no approved therapies are available. Because HCC is often driven by inflammation and is also associated with a suppressed immunoenvironment, there is a strong rationale to evaluate immunotherapy in patients with this type of cancer. The single-arm, multisite, phase 2 KEYNOTE-224 study (ClinicalTrials.gov, NCT02702414) was designed to evaluate the efficacy and safety of the anti–PD-1 antibody pembrolizumab in patients with previously treated advanced HCC. Methods: Approximately 100 patients will be enrolled. Inclusion criteria include age ≥18 years, histologically or cytologically confirmed diagnosis of HCC Barcelona Clinic Liver Cancer (BCLC) stage C disease or BCLC stage B disease not amenable to or refractory to locoregional therapy, and disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation). Patients must also have measurable disease based on RECIST v1.1 as confirmed by central imaging vendor review, documented objective radiographic progression after stopping treatment with sorafenib or intolerance to sorafenib, Child-Pugh liver score A, ECOG performance status 0-1, and predicted life expectancy > 3 months. Patients will be allocated to receive pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles (~2 years) or until disease progression, unacceptable toxicity, patient withdrawal of consent, or investigator decision. Response will be assessed every 9 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. The primary end point is objective response rate per RECIST v1.1 by central imaging vendor review. Secondary end points are overall survival; safety and tolerability; and duration of response, disease control rate, time to progression, and progression-free survival per RECIST v1.1 by central imaging vendor review. Enrollment in KEYNOTE-224 is ongoing. Clinical trial information: NCT02702414.

KEYNOTE-240: Randomized phase III study of pembrolizumab versus best supportive care for second-line advanced hepatocellular carcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS503-TPS503 ◽  
Author(s):  
Richard S. Finn ◽  
Stephen L. Chan ◽  
Andrew X. Zhu ◽  
Jennifer J. Knox ◽  
Ann-Lii Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Supportive Care ◽  
Disease Progression ◽  
Performance Status ◽  
Objective Response ◽  
Local Treatment ◽  
Best Supportive Care ◽  
Phase Iii ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma

TPS503 Background: There are no approved therapies for patients with hepatocellular carcinoma (HCC) after disease progression on sorafenib, or for patients with intolerance to sorafenib. HCC often arises in the background of chronic inflammation and is also associated with an immunosuppressed microenvironment, providing a strong rationale to evaluate immunotherapy in HCC. The randomized, double-blind, placebo-controlled phase 3 KEYNOTE-240 study (ClinicalTrials.gov, NCT02702401) was designed to compare the efficacy and safety of the anti–PD-1 antibody pembrolizumab + best supportive care (BSC) vs placebo + BSC in patients with previously treated advanced HCC. Methods: Eligibility criteria include age ≥18 years, confirmed diagnosis of Barcelona Clinic Liver Cancer (BCLC) stage C disease or BCLC stage B disease not amenable to or refractory to locoregional therapy, disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation), documented progression after treatment with sorafenib or intolerance to sorafenib, Child-Pugh liver score A, and ECOG performance status 0-1. ~408 patients will be randomly assigned 2:1 to receive pembrolizumab 200 mg IV every 3 weeks (Q3W) + BSC or placebo Q3W + BSC for up to 35 cycles or until disease progression, unacceptable toxicity, patient withdrawal of consent, or investigator decision. Randomization will be stratified by geographic region, macrovascular invasion, and α-fetoprotein. BSC will be provided by the investigator per local treatment practices. Response will be assessed every 6 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. Primary objectives are comparison of progression-free survival per RECIST v1.1 by central imaging vendor review and overall survival between treatment arms. Secondary objectives are comparison of objective response rate, duration of response, disease control rate, and time to progression per RECIST v1.1 by central imaging vendor review, and evaluation of safety and tolerability. Enrollment in KEYNOTE-240 is ongoing. Clinical trial information: NCT02702401.

Phase 3, randomized study of pembrolizumab (pembro) vs best supportive care (BSC) for second-line advanced hepatocellular carcinoma (HCC): KEYNOTE-240.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4143-TPS4143 ◽  
Author(s):  
Richard S. Finn ◽  
Stephen L. Chan ◽  
Andrew X. Zhu ◽  
Jennifer J. Knox ◽  
Ann-Lii Cheng ◽  
...  
Keyword(s):  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Randomized Study ◽  
Objective Response ◽  
Local Treatment ◽  
Standard Of Care ◽  
Advanced Hepatocellular Carcinoma ◽  
Phase 3 ◽  
Double Blind

TPS4143 Background: The tyrosine kinase inhibitor sorafenib is the standard of care for first-line HCC; currently, there is no clear standard of care after disease progression on sorafenib or for patients (pts) with intolerance to sorafenib. Because most HCC is driven by inflammation, there is a strong rationale to evaluate immunotherapy in pts with this type of cancer. The randomized, double-blind, placebo-controlled phase 3 KEYNOTE-240 study (ClinicalTrials.gov, NCT02702401) was designed to compare the efficacy and safety of the anti–PD-1 antibody pembro + BSC vs placebo + BSC in pts with previously treated advanced HCC. Methods: Eligibility criteria include age ≥ 18 years, histologically or cytologically confirmed diagnosis of HCC, documented progression after stopping treatment with sorafenib or intolerance to sorafenib, disease not amenable to a curative treatmentapproach (eg, transplantation, surgery, or ablation), measurable disease confirmed by central imaging vendor review per RECIST v1.1, Child-Pugh liver score A, ECOG performance status 0-1, and predicted life expectancy > 3 months. Pts will be randomly assigned 2:1 to receive pembro 200 mg IV Q3W + BSC or placebo Q3W + BSC for up to 35 cycles (~2 years) or until disease progression, unacceptable toxicity, or investigator decision. Randomization will be stratified by geographic region, presence of macrovascular invasion, and α-fetoprotein level. BSC will be provided by the investigator per local treatment practices. Response will be assessed every 6 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. Primary objectives are comparison of progression-free survival per RECIST v1.1 by central imaging vendor review and overall survival between treatment arms. Secondary objectives are comparison of objective response rate, duration of response, disease control rate, and time to progression per RECIST v1.1 by central imaging vendor review; and evaluation of safety and tolerability. Planned enrollment in KEYNOTE-240 is 408 pts across 26 countries. Clinical trial information: NCT02702401.

Nivolumab (NIVO) + ipilimumab (IPI) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Subgroup analyses from CheckMate 040.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
Aiwu Ruth He ◽  
Thomas Yau ◽  
Chiun Hsu ◽  
Yoon-Koo Kang ◽  
Tae-You Kim ◽  
...  
Keyword(s):  
Disease Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
The United States ◽  
Advanced Hepatocellular Carcinoma ◽  
Subgroup Analyses ◽  
Duration Of Response ◽  
Previously Treated ◽  
Grade 3

512 Background: NIVO monotherapy is approved in the United States and other countries for pts with HCC treated with sorafenib (SOR) based on CheckMate 040 (NCT01658878) results, which reported 14% objective response rate (ORR) and 16-month median overall survival (mOS; El-Khoueiry et al. Lancet 2017). Primary efficacy and safety of NIVO + IPI in pts with aHCC previously treated with SOR were presented recently (Yau et al. J Clin Oncol 2019). Here, we will present subgroup analyses from this study. Methods: Pts were randomized to 3 arms: [A] NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses) or [B] NIVO 3 mg/kg + IPI 1 mg/kg Q3W (4 doses), each followed by NIVO 240 mg Q2W, or [C] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included safety/tolerability, ORR, and duration of response (DOR; investigator assessment per RECIST v1.1). Key secondary endpoints included disease control rate (DCR), OS, and progression-free survival (blinded independent central review [BICR] per RECIST v1.1); key exploratory endpoints included ORR (BICR per RECIST v1.1). Data cutoff was January 2019. Results: A total of 148 pts were randomized. Minimum OS follow-up from last pt randomization date to data cutoff was 28 months. At baseline, 34% of all pts had vascular invasion; 82% had extrahepatic spread; and 91% had Barcelona Clinic Liver Cancer stage C; 84% discontinued SOR because of disease progression and 14% because of toxicity. For all treated pts, ORR was 31% (7 had complete response), with median DOR of 17 months; DCR was 49%; the 30-month OS rate was 37%. NIVO + IPI was well tolerated; 38% of pts had grade 3–4 treatment-related adverse events (TRAEs; most common any grade: pruritus and rash; most common grade 3–4: aspartate aminotransferase increase and lipase increase); 5% had grade 3–4 TRAEs leading to discontinuation. Subgroup analyses based on duration of prior SOR therapy and other pt characteristics will be presented. Conclusions: NIVO + IPI led to clinically meaningful benefits, with a manageable safety profile in pts previously treated with SOR. NIVO + IPI may provide a new treatment option for these pts. Clinical trial information: NCT01658878.

Phase II trial of sunitinib in bevacizumab-refractory metastatic renal cell carcinoma (mRCC): Updated results and analysis of circulating biomarkers

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5035-5035 ◽  
Author(s):  
D. J. George ◽  
M. D. Michaelson ◽  
J. E. Rosenberg ◽  
R. M. Bukowski ◽  
J. A. Sosman ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Clinical Response ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cross Resistance ◽  
Ecog Performance Status ◽  
Study Results ◽  
Pre Treatment

5035 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor activity. This study evaluated the safety and activity of sunitinib in mRCC patients (pts) previously treated with the VEGF-neutralizing antibody, bevacizumab. Levels of angiogenic biomarkers, including plasma VEGF and soluble VEGFR-3 (sVEGFR-3), were assessed for predictive significance with clinical response. Methods: Pts were required to have mRCC with disease progression following bevacizumab- based therapy, measurable disease, ECOG performance status 0 or 1, and adequate organ function. Pts were treated with sunitinib 50 mg daily in 6-week cycles (4 weeks on, followed by 2 weeks off). The primary endpoint was objective response according to RECIST. Plasma VEGF and sVEGFR-3 levels were measured in pre-treatment samples and at multiple timepoints on study. Results: A total of 61 pts were enrolled. The objective partial response rate was 23% (95% CI: 13%, 36%); 35 pts (57%) demonstrated stable disease. The median duration of response was 36 weeks (95% CI: 26, NA) and progression-free survival was 30 weeks (95% CI: 18, 34). Plasma VEGF levels increased from baseline (3-fold mean elevation), while plasma sVEGFR-3 levels decreased from baseline (40% mean reduction). Pre-treatment VEGF levels were significantly higher in pts (n=34) with <10 weeks between cessation of bevacizumab and start of sunitinib (p<0.001); ELISA specificity suggests that detected VEGF is not bevacizumab-bound. Pre-treatment sVEGFR-3 levels were significantly lower at baseline in responding pts vs. non-responding pts (p<0.0318). A greater reduction in sVEGFR-3 levels was seen in responding pts vs. non-responding pts (p<0.10). Pretreatment VEGF and VEGF fold-changes did not differ according to clinical response. Conclusions: Sunitinib has significant antitumor activity in bevacizumab-refractory mRCC pts, suggesting absence of cross-resistance between bevacizumab and sunitinib. Biomarkers including plasma VEGF and sVEGFR-3 may have predictive potential in sunitinib-treated patients. No significant financial relationships to disclose.

scholarly journals Efficacy, Safety, and Potential Biomarkers of Sunitinib Monotherapy in Advanced Hepatocellular Carcinoma: A Phase II Study

2009 ◽  
Vol 27 (18) ◽  
pp. 3027-3035 ◽  
Author(s):  
Andrew X. Zhu ◽  
Dushyant V. Sahani ◽  
Dan G. Duda ◽  
Emmanuelle di Tomaso ◽  
Marek Ancukiewicz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Sunitinib Treatment

PurposeTo assess the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) and explore biomarkers for sunitinib response.Patients and MethodsWe conducted a multidisciplinary phase II study of sunitinib, an antivascular endothelial growth factor receptor tyrosine kinase inhibitor, in advanced HCC. Patients received sunitinib 37.5 mg/d for 4 weeks followed by 2 weeks of rest per cycle. The primary end point was progression-free survival (PFS). We used functional magnetic resonance imaging to evaluate vascular changes in HCC after sunitinib treatment. Circulating molecular and cellular biomarkers were evaluated before and at six time points after sunitinib treatment.ResultsThirty-four patients were enrolled. The objective response rate was 2.9%, and 50% of patients had stable disease. Median PFS was 3.9 months (95% CI, 2.6 to 6.9 months), and overall survival was 9.8 months (95% CI, 7.4 months to not available). Grade 3 or 4 toxicities included leukopenia/neutropenia, thrombocytopenia, elevation of aminotransferases, and fatigue. Sunitinib rapidly decreased vessel leakiness, and this effect was more pronounced in patients with delayed progression. When evaluated early (at baseline and day 14) as well as over three cycles of treatment, higher levels of inflammatory molecules (eg, interleukin-6, stromal-derived factor 1α, soluble c-KIT) and circulating progenitor cells were associated with a poor outcome.ConclusionSunitinib shows evidence of modest antitumor activity in advanced HCC with manageable adverse effects. Rapid changes in tumor vascular permeability and circulating inflammatory biomarkers are potential determinants of response and resistance to sunitinib in HCC. Our study suggests that control of inflammation might be critical for improving treatment outcome in advanced HCC.

A study of ramucirumab (LY3009806) versus placebo in patients with hepatocellular carcinoma and elevated baseline alpha-fetoprotein (REACH-2).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS538-TPS538 ◽  
Author(s):  
Andrew X. Zhu ◽  
Peter R. Galle ◽  
Masatoshi Kudo ◽  
Richard S. Finn ◽  
Shukui Qin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Progression ◽  
Objective Response ◽  
Primary Objective ◽  
Alpha Fetoprotein ◽  
Chinese Patients ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Meaningful Improvement

TPS538 Background: Ramucirumab (RAM), a human IgG1 mAb, inhibits ligand activation of VEGFR2. In REACH, while improvement in overall survival (OS) in the overall population was not statistically significant, meaningful improvement was observed in a patient subgroup with baseline alpha-fetoprotein (AFP) ≥400 ng/mL (N = 250) (HR = 0.67, p = 0.006; median OS [months] RAM 7.8 vs placebo [pbo] 4.2). RAM treatment was generally well tolerated in patients with advanced hepatocellular carcinoma (HCC) after prior sorafenib (SOR). Methods: REACH-2 is a randomized, double-blind, pbo-controlled, global phase 3 study of RAM+best supportive care (BSC) vs pbo+BSC in patients with HCC and elevated baseline AFP following therapy with SOR. Eligibility includes Child-Pugh < 7; Barcelona Clinic Liver Cancer Stage C or B disease not amenable/refractory to locoregional therapy; AFP ≥400 ng/mL; ECOG PS 0 or 1; ≥1 measurable lesion; and disease progression during/after SOR, or SOR intolerance. Patients with history of hepatic encephalopathy, clinically meaningful ascites, liver transplant, or hepatic locoregional therapy after SOR are not eligible. Eligible patients will be randomized 2:1 to 8 mg/kg RAM or pbo (14-day cycle) and treated until radiographic/clinical disease progression or discontinuation criteria are met. The primary objective is OS; secondary objectives include progression-free survival (PFS), objective response rate, safety, and patient-focused outcomes. Recognizing expanding treatment options for HCC, a second, single arm, open-label cohort of ~44 patients will be enrolled with the same eligibility and treatment as the main cohort except a requirement for prior treatment other than SOR (eg, mTKIs, immune checkpoint inhibitors) and some exclusions of checkpoint inhibitor-related adverse events. The primary objective is safety; secondary objectives include OS, PFS, and patient-focused outcomes. Additionally, a third randomized cohort of ~65 Chinese patients will be enrolled with the same objectives, eligibility, treatment, and evaluations as the main cohort. Analysis of Open-Label and Chinese cohorts will be independent of the main REACH-2 cohort. Clinical trial information: NCT02435433.

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

Liver Cancer ◽  
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

<b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

2017 ◽  
Vol 35 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Effective Treatment Option ◽  
Sorafenib Treatment ◽  
Advanced Hcc ◽  
Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

scholarly journals Avelumab in Combination with Axitinib as First-Line Treatment in Patients with Advanced Hepatocellular Carcinoma: Results from the Phase 1b VEGF Liver 100 Trial

Liver Cancer ◽  
2021 ◽  
pp. 1-11
Author(s):  
Masatoshi Kudo ◽  
Kenta Motomura ◽  
Yoshiyuki Wada ◽  
Yoshitaka Inaba ◽  
Yasunari Sakamoto ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Kinase Inhibitor ◽  
Group Performance ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Clinical Activity ◽  
Advanced Hepatocellular Carcinoma ◽  
Recist 1.1 ◽  
Phase 1B ◽  
Grade 3

<b><i>Introduction:</i></b> Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for the treatment of advanced/metastatic hepatocellular carcinoma (aHCC). Avelumab is a human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We report the final analysis from VEGF Liver 100 (NCT03289533), a phase 1b study evaluating safety and efficacy of avelumab plus axitinib in treatment-naive patients with aHCC. <b><i>Methods:</i></b> Eligible patients had confirmed aHCC, no prior systemic therapy, ≥1 measurable lesion, Eastern Cooperative Oncology Group performance status ≤1, and Child-Pugh class A disease. Patients received avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily until progression, unacceptable toxicity, or withdrawal. Endpoints included safety and investigator-assessed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) for HCC. <b><i>Results:</i></b> Twenty-two Japanese patients were enrolled and treated with avelumab plus axitinib. The minimum follow-up was 18 months as of October 25, 2019 (data cutoff). Grade 3 treatment-related adverse events (TRAEs) occurred in 16 patients (72.7%); the most common (≥3 patients) were hypertension (<i>n</i> = 11 [50.0%]), palmar-plantar erythrodysesthesia syndrome (<i>n</i> = 5 [22.7%]), and decreased appetite (<i>n</i> = 3 [13.6%]). No grade 4 TRAEs or treatment-related deaths occurred. Ten patients (45.5%) had an immune-related AE (irAE) of any grade; 3 patients (13.6%) had an infusion-related reaction (IRR) of any grade, and no grade ≥3 irAE and IRR were observed. The objective response rate was 13.6% (95% CI: 2.9–34.9%) per RECIST 1.1 and 31.8% (95% CI: 13.9–54.9%) per mRECIST for HCC. <b><i>Conclusion:</i></b> Treatment with avelumab plus axitinib was associated with a manageable toxicity profile and showed antitumor activity in patients with aHCC.

Clinical Outcomes of 2nd- and 3rd-Line Regorafenib for Advanced Hepatocellular Carcinoma

Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Kensuke Naruto ◽  
Tomokazu Kawaoka ◽  
Kei Amioka ◽  
Yutaro Ogawa ◽  
Kikukawa Chihiro ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcomes ◽  
Median Overall Survival ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Free Survival ◽  
Line Therapy ◽  
Unresectable Hepatocellular Carcinoma

<b><i>Introduction:</i></b> This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. <b><i>Methods:</i></b> In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. <b><i>Results:</i></b> There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. <b><i>Conclusion:</i></b> Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.

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