Axitinib in combination with radiotherapy for advanced hepatocellular carcinoma: a phase I clinical trial

Abstract Background To investigate maximum tolerated dose (MTD) of axitinib, a selective vascular endothelial growth factor receptor 1–3 inhibitor, in combination with radiotherapy (RT) for advanced hepatocellular carcinoma (HCC). Methods This phase I study followed the rule of traditional 3 + 3 design. Major eligibility included: (1) patients with advanced HCC unsuitable for surgery, radiofrequency ablation or transarterial chemoembolization, or who failed after prior local–regional treatment; (2) failure on sorafenib or no grant for sorafenib from health insurance system. Eligible patients with advanced HCC received axitinib for total 8 weeks during and after RT. Three cohorts with axitinib dose escalation were planned: 1 mg twice daily (level I), 2 mg twice daily (level II) and 3 mg twice daily (level III). The prescribed doses of RT ranged from 37.5 to 67.5 Gy in 15 fractions to liver tumor(s) and were determined based on an upper limit of mean liver dose of 18 Gy (intended isotoxic RT for normal liver). The primary endpoint was MTD of axitinib in combination with RT. The secondary endpoints included overall response rate (ORR), RT in-field response rate, acute and late toxicities, overall survival (OS) and progression free survival (PFS). Results Total nine eligible patients received axitinib dose levels of 1 mg twice daily (n = 3), 2 mg twice daily (n = 3) and 3 mg twice daily (n = 3). Dose-limiting toxicity (DLT) did not occur in the 3 cohorts; the MTD was defined as 3 mg twice daily in this study. ORR was 66.7%, including 3 complete responses and 3 partial responses, at 3 months after treatment initiation. With a median follow-up of 16.6 months, median OS was not reached, 1-year OS was 66.7%, and median PFS was 7.4 months. Conclusions Axitinib in combination with RT for advanced HCC was well tolerated with an axitinib MTD of 3 mg twice daily in this study. The outcome analysis should be interpreted with caution due to the small total cohort. Trial registration ClinicalTrials.gov (Identifier: NCT02814461), Registered June 27, 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02814461

Download Full-text

Axitinib in Combination with Radiotherapy for Advanced Hepatocellular Carcinoma: A Phase I Clinical Trial

10.21203/rs.3.rs-38081/v1 ◽

2020 ◽

Author(s):

Kai-Lin Yang ◽

Mau-Shin Chi ◽

Hui-Ling Ko ◽

Yi-Ying Huang ◽

Su-Chen Huang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase I ◽

Phase I Study ◽

Locally Advanced ◽

Progression Free Survival ◽

Normal Liver ◽

Maximum Tolerated Dose ◽

Outcome Analysis ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Hcc

Abstract Background: Axitinib is a selective vascular endothelial growth factor receptors 1–3 inhibitor approved for second-line treatment of advanced renal cell carcinoma. In a randomized, placebo-controlled phase II trial for patients with locally advanced or metastatic hepatocellular carcinoma (HCC), axitinib improved progression-free survival and showed overall response rate of 9.7%. This phase I study aimed at evaluating maximum tolerated dose (MTD) of axitinib in combination with radiotherapy (RT) for advanced hepatocellular carcinoma (HCC).Methods: This phase I study followed the rule of traditional 3 + 3 design. Major eligibility included: (1) advanced HCC unsuitable for surgery, radiofrequency ablation or transarterial chemoembolization; (2) failure on sorafenib or no grant for sorafenib from health insurance system. Eligible patients with advanced HCC received axitinib for total 8 weeks during and after RT. Three cohorts with axitinib dose escalation were planned: 1 mg twice daily (level I), 2 mg twice daily (level II) and 3 mg twice daily (level III). The prescribed doses of RT ranged from 37.5 to 67.5 Gy in 15 fractions to liver tumor(s) and were determined based on an upper limit of mean liver dose of 18 Gy (intended isotoxic RT for normal liver). The primary endpoint was MTD of axitinib in combination with RT.Results: Total nine eligible patients received axitinib dose levels of 1 mg twice daily (n = 3), 2 mg twice daily (n = 3) and 3 mg twice daily (n = 3). Dose-limiting toxicity (DLT) did not occur in the 3 cohorts; the MTD was defined as 3 mg twice daily in this study. ORR was 66.7%, including 3 complete responses and 3 partial responses, at 3 months after treatment initiation. With a median follow-up of 16.6 months, median OS was not reached, 1-year OS was 66.7%, and median PFS was 7.4 months.Conclusions: Axitinib in combination with RT for advanced HCC was well tolerated with an axitinib MTD of 3 mg twice daily in this study. The outcome analysis should be interpreted with caution due to the small total cohort.Trial registration: ClinicalTrials.gov (Identifier: NCT02814461), Registered June 27, 2016 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02814461

Download Full-text

Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.3301 ◽

2009 ◽

Vol 27 (6) ◽

pp. 843-850 ◽

Cited By ~ 231

Author(s):

Melanie B. Thomas ◽

Jeffrey S. Morris ◽

Romil Chadha ◽

Michiko Iwasaki ◽

Harmeet Kaur ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Response Rate ◽

Group Performance ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Evaluation Criteria ◽

Progression Free Survival ◽

Advanced Hepatocellular Carcinoma ◽

Study Objective ◽

Advanced Hcc

Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. Results The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). Conclusion The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

Download Full-text

Phase Ib trial of tepotinib in Asian patients with advanced hepatocellular carcinoma (HCC): Final data including long-term outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.4087 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 4087-4087 ◽

Cited By ~ 2

Author(s):

Shukui Qin ◽

Tae-You Kim ◽

Ho Yeong Lim ◽

Baek-Yeol Ryoo ◽

Jürgen Scheele ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Progression Free Survival ◽

Response Duration ◽

Complete Response ◽

Maximum Tolerated Dose ◽

Advanced Hepatocellular Carcinoma ◽

Modest Improvement ◽

Phase Ib ◽

Advanced Hcc ◽

Ecog Ps

4087 Background: The incidence of hepatocellular carcinoma (HCC), a leading cause of cancer death, is increasing with the increasing incidence of chronic liver disease. Sorafenib, the only approved systemic therapy for advanced HCC, provides modest improvement in overall survival. Preclinical studies suggest c-Met is a valid target in HCC, but non-selective TKIs with c-Met inhibitory activity have not shown efficacy in trials, possibly due to lack of c-Met inhibition. Tepotinib (MSC2156119J) is a highly selective c-Met inhibitor that has favorable safety and promising activity, particularly against c-Met+ solid tumors. We report the final results of a phase Ib trial of tepotinib in patients (pts) with advanced HCC. Methods: Pts were Asian adults with confirmed HCC of BCLC Stage C, Child-Pugh Class A liver function without encephalopathy, and ECOG PS 0–2. Pts received tepotinib 300, 500 (the RP2D) or 1,000 mg/day on a 21-day cycle. c-Met expression status was retrospectively determined by IHC. Results: 27 pts were enrolled (median age 57 [38-69]; male 23; ECOG PS 0/1 11/16); 7 received tepotinib 300 mg/day, 14 500 mg/day, and 6 1,000 mg/day (3 with dose reduction). No DLTs were observed. 22 pts experienced treatment-related treatment-emergent adverse events (TRTEAEs), most commonly diarrhea (n = 10), nausea (8), elevated AST (7), and elevated ALT (6). 9 pts had grade ≥3 TRTEAEs, including elevated AST (3) and elevated ALT (3). Best overall response (BOR) was partial response (PR) in 2 pts, one of whom received tepotinib 500 mg (response duration 16.1 months) and one 1,000 mg (4.4 months); both had c-Met+ tumors. A further 8 pts had a BOR of stable disease (SD), 1 pt non-complete response (CR)/non-progressive disease (PD), and 14 pts had PD (2 pts not evaluable). Five pts had progression free survival > 8 months. PK were as expected from previous studies. Conclusions: Tepotinib at doses of up to 1,000 mg/day was well tolerated by Asian pts with advanced HCC and a maximum tolerated dose was not reached. Antitumor activity was observed, particularly in pts with c-Met+ tumors. The ongoing phase II part of this study is comparing the efficacy and safety of first-line tepotinib and sorafenib in pts with c-Met+ HCC. Clinical trial information: NCT01988493.

Download Full-text

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

Journal of Clinical Oncology ◽

10.1200/jco.2008.20.9908 ◽

2009 ◽

Vol 27 (18) ◽

pp. 3027-3035 ◽

Cited By ~ 327

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.

Download Full-text

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

Digestive Diseases ◽

10.1159/000480257 ◽

2017 ◽

Vol 35 (6) ◽

pp. 611-617 ◽

Cited By ~ 9

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.

Download Full-text

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

Oncology ◽

10.1159/000515280 ◽

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

Introduction: This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. Methods: 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. Results: 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. Conclusion: 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.

Download Full-text

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma by placing a temporary catheter via the subclavian route

Acta Radiologica ◽

10.1080/02841850701408210 ◽

2007 ◽

Vol 48 (7) ◽

pp. 734-740 ◽

Cited By ~ 5

Author(s):

Huei-Lung Liang ◽

Jer-Shyung Huang ◽

Yi-Huei Lin ◽

Kwok-Hung Lai ◽

Chien-Fang Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Response Rate ◽

Hepatic Arterial Infusion ◽

Catheter Placement ◽

Hepatic Arterial Infusion Chemotherapy ◽

Advanced Hepatocellular Carcinoma ◽

Arterial Infusion ◽

Arterial Infusion Chemotherapy ◽

Advanced Hcc ◽

Infusion Chemotherapy

Background: A permanent reservoir implantation is considered mandatory for hepatic arterial infusion chemotherapy (HAIC) of hepatocellular carcinoma (HCC). Since treatment sessions of HAIC may be limited for these end-staged patients, a simple alternative technique for this treatment is desirable. Purpose: To evaluate the feasibility of placing a temporary catheter for HAIC in advanced HCC patients. Material and Methods: 25 advanced HCC patients underwent HAIC with drugs delivered from a temporary catheter which was placed percutaneously by puncturing the left subclavian artery under ultrasound guidance. A course of chemotherapy consisted of five consecutive daily infusions of 5-fluorouracil, cisplatin, mitomycin C, and leucovorin. The catheter was removed on the 6th day. Therapy was repeated every 4–6 weeks with maximal number of courses of up to six. The total courses of HAIC in each patient, the catheter-placed-related complications, tumor response rate, and median survival of the patients were registered. Results: A total of 77 courses of HAIC were performed with 100% technical success of catheter placement (1–6 courses in each patient, average 3.1 courses). The overall response rate was 20%, with complete response in two patients and partial response in three patients. Eleven (55%) of the 20 non-responders died within 5 months (mean HAIC, two courses). None of the patients experienced complications such as catheter occlusion, hepatic arterial thrombosis, cerebral infarction, or local infection. Conclusion: With fewer catheter-related complications, HAIC by temporary catheter placement via subclavian puncture could be a treatment option.

Download Full-text

Hepatic Arterial Infusion Chemotherapy Combined With PD-1 Inhibitors Plus Lenvatinib Versus PD-1 Inhibitors Plus Lenvatinib for Advanced Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2021.618206 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jie Mei ◽

Yu-Hao Tang ◽

Wei Wei ◽

Ming Shi ◽

Lie Zheng ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatic Arterial Infusion ◽

Progression Free Survival ◽

Good Survival ◽

Hepatic Artery Infusion ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Hcc ◽

Infusion Chemotherapy ◽

Hepatic Artery Infusion Chemotherapy ◽

Cell Death Protein

BackgroundLenvatinib combined with programmed cell death protein-1 (PD-1) inhibitors has resulted in good survival outcomes in the treatment of unresectable hepatocellular carcinoma (HCC). Hepatic artery infusion chemotherapy (HAIC) has also attracted attention due to its high response rates and favorable survival for advanced HCC patients. The present study aimed to compare the efficacy of HAIC combined with PD-1 inhibitors plus lenvatinib (HPL) and PD-1 inhibitors plus lenvatinib (PL) in patients with advanced HCC.MethodsBetween July 2018 and December 2019, patients diagnosed with advanced HCC who initially received HPL or PL treatment were reviewed for eligibility. Efficacy was evaluated according to tumor response and survival.ResultsIn total, 70 patients met the criteria and were included in the present study, and they were divided into the HPL group (n = 45) and PL group (n = 25). The overall response rate (40.0 vs. 16.0%, respectively; p = 0.038) and disease control rate (77.6 vs. 44.0%, respectively; p < 0.001) were higher in the HPL group than in the PL group. The median overall survival was 15.9 months in the HPL group and 8.6 months in the PL group (p = 0.0015; HR = 0.6; 95% CI 0.43–0.83). The median progression-free survival was 8.8 months in the HPL group and 5.4 months in the PL group (p = 0.0320; HR = 0.74; 95% CI 0.55–0.98).ConclusionCompared to PL, HPL was associated with a significantly better treatment response and survival benefits for patients with advanced HCC.

Download Full-text

Phase II study of intrabuccally-administered amplitude-modulated electromagnetic fields in patients with advanced hepatocellular carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15573 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15573-e15573

Author(s):

F. P. Costa ◽

A. C. de Oliveira ◽

R. Meirelles ◽

M. M. Machado ◽

R. Surjan ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Electromagnetic Fields ◽

Phase Ii ◽

Phase Ii Study ◽

Progression Free Survival ◽

Hepatic Function ◽

Advanced Hepatocellular Carcinoma ◽

Free Survival ◽

Advanced Hcc ◽

Independent Review

e15573 Background: Over the past few years we have identified tumor-specific frequencies for several common forms of cancer. The goal of this study was to assess the tolerability and effectiveness of electromagnetic fields amplitude-modulated at tumor-specific frequencies and administered by means of an intrabuccal spoon-shaped probe in patients with advanced hepatocellular carcinoma (HCC). Methods: From October 2005 to July 2007, patients with advanced HCC and Child-Pugh A or B were recruited in a phase II study. Three daily 60 min outpatient treatments were administered until disease progression or death. Imaging studies were performed every eight weeks. The primary efficacy end point was progression-free survival ≥ 6 months. Secondary efficacy end points were progression-free survival and overall survival. Results: A total of 41 patients were enrolled, 17 had Child-Pugh A, 20 Child-Pugh B disease. The median age was 64.0 years. Seventeen patients (34.1%) were progression-free for more than 6 months. Median progression-free and overall survivals were 4.8 months (95% CI 2.3–6.0) and 6.9 months (95 CI 4.8–11.1). As of December 2008, four patients are alive and two patients, who are still undergoing therapy, remain progression-free for 30.4 and 30.7 months, respectively. Four patients had partial response (9.8%) and sixteen had stable disease for at least 12 weeks (39.0%) according to the RECIST criteria resulting in 48.8% disease control. All responses were confirmed by independent review. There were no NCI grade 2, 3 or 4 toxicities. One patient developed grade 1 mucositis and one patient grade 1 fatigue. Conclusions: In patients with advanced HCC and impaired hepatic function, treatment with amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of anti-tumor effects, which are long-lasting in some patients. No significant financial relationships to disclose.

Download Full-text

Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict efficacy of axitinib for treatment of advanced hepatocellular carcinoma (HCC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e15656 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e15656-e15656 ◽

Cited By ~ 1

Author(s):

Po-Hsiang Huang ◽

Bang-Bin Chen ◽

Zhong-Zhe Lin ◽

Ying-Chun Shen ◽

Yee Chao ◽

...

Keyword(s):

Liver Tumors ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

University Hospital ◽

Advanced Hepatocellular Carcinoma ◽

Quantitative Parameter ◽

Sorafenib Treatment ◽

Dce Mri ◽

Advanced Hcc ◽

Disease Stabilization

e15656 Background: Axitinib, a potent inhibitor of vascular endothelial growth factor receptor, has moderate antitumor efficacy for advanced HCC. Vascular response (VR) measured by DCE-MRI has been demonstrated to correlate with efficacy of systemic therapy for advanced HCC. Methods: Patients enrolled into a phase 2 trial of axitinib as second-line therapy for advanced HCC (NCT01273662) with liver tumors evaluable by DCE-MRI were included. Patients must have documented progression on or intolerance to sorafenib and Child-Pugh class A liver function. The primary endpoint was disease stabilization, defined as complete or partial response per RECIST1.1 or stable disease lasting for 8 weeks without progression of tumor-related symptoms. The quantitative parameter Ktrans and semi-quantitative parameter peak, measured by DCE-MRI at baseline and after 2 weeks of axitinib treatment, were used to evaluate VR, defined by a greater than 40% decrease of Ktrans or peak. Results: From April 2011 to March 2016, 40 patients were enrolled at National Taiwan University Hospital and 5 at Taipei Veterans General Hospital, all had documented progression after sorafenib treatment. Disease stabilization rate was 62.2% (95% CI 48.0-76.4). Median progression-free survival (PFS) and overall survival (OS) were 2.2 months (95% CI 0.3-4.1) and 10.1 months (95% CI 3.6-16.5) respectively. 33 patients were evaluable for VR. VR evaluated by peak was significantly associated with better PFS (5.5 vs. 1.8 months, HR 0.41, 95% CI 0.16-1.02, p = 0.04) and OS (13.0 vs. 5.8 months, HR 0.28, 95% CI 0.09-0.85, p = 0.02). Treatment-related adverse events were compatible with previous reports of axitinib. Conclusions: VR measured by DCE-MRI may help identify HCC patients most likely to benefit from axitinib treatment. Clinical trial information: NCT01273662. [Table: see text]

Download Full-text