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 Regorafenib Combined With Sintilimab Versus Regorafenib as Second-line Treatment for Advanced Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Jingjun Huang ◽  
Yongjian Guo ◽  
Wensou Huang ◽  
Zining Xu ◽  
Liteng Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Objective Response ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
Second Line ◽  
Free Survival ◽  
Advanced Hcc ◽  
Grade 3

Abstract Purpose: To evaluate the safety and efficacy of regorafenib combined with immune checkpoint inhibitor sintilimab (rego-sintilimab) as second-line treatment for advanced hepatocellular carcinoma (HCC) patients who failed prior sorafenib or lenvatinib.Methods: This retrospective study evaluated consecutive patients with advanced HCC who received rego-sintilimab (rego-sintilimab group) or regorafenib alone (regorafenib group) as second-line treatment from January 2019 to December 2020. Adverse events, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Results: Eighty-three patients were included: 48 received rego-sintilimab and 35 received regorafenib. Rego-sintilimab group had higher ORR (33.3% vs 14.3%, P =.049), longer PFS (median, 5.1 vs 3.0 months; P =.001), and better OS (median, 13.3 vs 9.1 months; P =.001) than regorafenib group. Regorafenib alone, Child-Pugh B, and neutrophil-to-lymphocyte ratio (NLR) >3.5 were independent prognostic factors for poor OS in uni- and multi-variable analyses. Subgroup analyses showed that, in patients with Child-Pugh A (16.4 vs 11.5 months; P =.005), Child-Pugh B (8.8 vs 6.4 months; P =.032), or NLR ≤3.5 (16.3 vs 11.5 months; P =.012), rego-sintilimab group had significantly better median OS than regorafenib group, whereas median OS was not significantly different between the two groups in patients with NLR >3.5 (8.4 vs 7.0 months; P =.288). The incidences of grade 3/4 adverse events were similar between the two groups (39.4% vs 34.1%; P =.445).Conclusion: Rego-sintilimab was tolerable and led to better OS than regorafenib as second-line treatment for advanced HCC patients, especially in those with NLR ≤3.5.

Sorafenib versus cytotoxic chemotherapy for patients with advanced hepatocellular carcinoma: A retrospective, single-institution study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 339-339
Author(s):  
S. Lee ◽  
S. Yoon ◽  
S. Shin ◽  
H. Choi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Cytotoxic Chemotherapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Chemotherapy Group ◽  
Sorafenib Group ◽  
The Difference ◽  
Grade 3 ◽  
Novel Target

339 Background: Prior to the sorafenib era, most of the advanced hepatocellular carcinoma (HCC) patients had to rely only on conventional cytotoxic chemotherapy. But the introduction of sorafenib in 2008 had given HCC patients additional option for their treatment. However, given that sorafenib has been a nonreimbursable drug under the Korea public health system, most of treatment strategy has largely been determined by patients' affordability of the drug rather than by difference in efficacy and toxicity of the two treatments. Therefore, we compared the efficacy and toxicity of the two treatments by observing HCC patients. Methods: From January 2002 to December 2009, 173 patients with unresectable HCC had been retrospectively analyzed. Among them, 44 (25.4%) had been treated with sorafenib and the remaining had received cytotoxic chemotherapy. We evaluated objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results: The median OS of sorafenib group was 23.0 weeks (95% CI, 8.1-37.9) vs. 43.6 weeks (95% CI, 34.0-37.9) for cytotoxic chemotherapy group. The median PFS for sorafenib group was 11.1 weeks (95% CI, 6.5-15.8) versus 12.4 weeks (95% CI, 8.1-16.7) for cytotoxic chemotherapy group. However, the difference in both findings had not been statistically significant (p=0.105 and p=0.496, respectively). ORR and DCR for sorafenib group were 2.3% and 52.3% versus 6.2% and 43.4% for cytotoxic chemotherapy group, respectively. Patients treated with chemotherapy had shown higher frequencies of grade 3 or 4 neutropenia, 19.7%, (vs. 0% for sorafenib). However, the group with sorafenib had reported a higher rate of all grade dermatologic toxicities such as hand-foot skin reaction, rash and pruritus. Conclusions: Our analysis indicates that efficacy of conventional chemotherapy is not inferior to that of sorafenib. Further research including novel target agent and cytotoxic chemotherapy is needed to improve clinical outcomes for advanced HCC. No significant financial relationships to disclose.

Evaluation of patupilone as monotherapy in patients with advanced hepatocellular carcinoma (HCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15055-15055 ◽  
Author(s):  
A. P. Venook ◽  
R. Poon ◽  
Y. K. Kang ◽  
T. S. Mok ◽  
Y. Chao ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Objective Response ◽  
Study Drug ◽  
Progression Free Survival ◽  
Hepatic Function ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Vein Thrombosis ◽  
Grade 3 ◽  
Stage 1

15055 Background: Currently, there is no strong evidence that systemic therapies provide a survival benefit for patients (pts) with hCC. However, preclinical data have shown that the novel epothilone patupilone has potent anti-proliferative activity against 8 HCC cell lines with intrinsic multidrug resistance. This exploratory study tested whether patupilone monotherapy has antitumor activity in HCC patients with intact liver function. Methods: This open-label, single-arm, multicenter, 2-stage phase II study was to enroll 24 pts in the first stage and 41 pts in the second stage, if = 3 complete or partial responses were observed in the first stage. Patients with unresectable and/or metastatic HCC (histologically confirmed) with = 1 measurable lesion were eligible if they had well-preserved hepatic function (Child-Pugh Class A) and life expectancy = 3 months. Patupilone was administered as a single IV infusion at 10 mg/m2 over 20 minutes every 3 weeks. Primary endpoint was objective response. Results: Twenty-five patients were enrolled, 24 were evaluable, and 1 violated protocol. The most common adverse events (AEs) suspected to be study-drug related were NCI CTC grade 1/2 diarrhea, fatigue, and vomiting. Grade 4 serious AEs included hyponatremia (2 pts [8%]), cardiac arrest (1 pt [4%]), diarrhea (1 pt [4%]), and gastrointestinal hemorrhage (1 pt [4%]). Grade 3 serious AEs included diarrhea (3 pts [12%]), hyponatremia (2 pts [8%]), deep vein thrombosis (1 pt [4%]), abdominal pain (1 pt [4%]), and hyperkalemia (1 pt [4%]). Most pts had dose adjustments or delays; 3 discontinued treatment. During the first stage, 1 pt had a confirmed partial response through 4 cycles, and 11 pts (44%) had stable disease for = 2 cycles with a median of 4 cycles (range, 2 to 8 cycles). Median progression-free survival was 3 months (range, 1 to 6 months), and 10 pts (40%) progressed within the first 2 cycles. The study did not progress to stage 2. Conclusions: Patupilone demonstrated an acceptable safety profile. Serious AEs were observed in a minority of patients, and most did not require treatment discontinuation. Patupilone demonstrated only modest antitumor activity in pts with HCC in this study. No significant financial relationships to disclose.

Real-Life Clinical Practice with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Center Experience Second Analysis

2015 ◽  
Vol 33 (6) ◽  
pp. 728-734 ◽  
Author(s):  
Tadaaki Arizumi ◽  
Kazuomi Ueshima ◽  
Mina Iwanishi ◽  
Hirokazu Chishina ◽  
Masashi Kono ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Response ◽  
Objective Response ◽  
Real Life ◽  
Progression Free Survival ◽  
University Hospital ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Single Center ◽  
Grade 3

Objectives: Sorafenib has become a standard therapy for advanced hepatocellular carcinoma following the demonstration of significant increase in progression-free survival as well as overall survival (OS) in the 2-phase III trials. We examined efficacy and adverse events (AEs) in patients treated with sorafenib over a 6-year period since approval in Japan. Methods: Two hundred and forty-one patients treated with sorafenib at the Kinki University Hospital were retrospectively analyzed clinically for the factors related to survival periods, tumor response evaluated by the Response Evaluation Criteria In Cancer of the Liver (RECICL) and AEs. Results: OS was 14.3 months. According to the RECICL, the objective response and disease control rates were 18.6% (43 of 241) and 61.1% (137 of 241), respectively. AEs were seen in 77.3% (187 of 241), with Grade 3 or higher in 23.6% (57 of 241). The most frequent AE was hand-foot skin reaction in 109 patients (45.0%), and 28 patients (11.8%) showed Grade 3 or higher. Significant factors contributing to the OS were treatment duration (p = 0.0204), up-to-7 criteria (p = 0.0400), increase of Child-Pugh score (p = 0.0008) and tumor response determined by the RECICL (p = 0.0007). Conclusion: Based on the analysis, using many cases at a single center, we concluded that continuation of treatment with sorafenib for ≥90 days without decrease of liver function was critical if tumor response was determined as stable disease or higher.

Phase II Study of Gemcitabine and Oxaliplatin in Combination With Bevacizumab in Patients With Advanced Hepatocellular Carcinoma

2006 ◽  
Vol 24 (12) ◽  
pp. 1898-1903 ◽  
Author(s):  
Andrew X. Zhu ◽  
Lawrence S. Blaszkowsky ◽  
David P. Ryan ◽  
Jeffrey W. Clark ◽  
Alona Muzikansky ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Vascular Tumor ◽  
Advanced Hepatocellular Carcinoma ◽  
Close Monitoring ◽  
Grade 3 ◽  
Transient Elevation

Purpose Hepatocellular carcinoma (HCC) is a vascular tumor with poor prognosis. Given the reported activity of gemcitabine and oxaliplatin (GEMOX) in HCC and the potential benefits of targeting the vascular endothelial growth factor pathway with bevacizumab (B), a phase II study of GEMOX-B was undertaken to define efficacy and toxicity profiles in HCC patients. Patients and Methods Eligible patients had pathologically proven measurable unresectable or metastatic HCC. For cycle 1 (14 days), bevacizumab 10 mg/kg was administered alone intravenously on day 1. For cycle 2 and beyond (28 days/cycle), bevacizumab 10 mg/kg was administered on days 1 and 15, gemcitabine 1,000 mg/m2 was administered as a dose rate infusion at 10 mg/m2/min followed by oxaliplatin at 85 mg/m2 on days 2 and 16. Results Thirty-three patients were enrolled and 30 patients were assessable for efficacy. The objective response rate was 20%, and 27% of patients had stable disease. Median overall survival was 9.6 months (95% CI, 8.0 months to not available) and median progression-free survival (PFS) was 5.3 months (95% CI, 3.7 to 8.7 months); the PFS rate at 3 and 6 months was 70% (95% CI, 54% to 85%) and 48% (95% CI, 31% to 65%), respectively. The most common treatment-related grade 3 to 4 toxicities included leukopenia/neutropenia, transient elevation of aminotransferases, hypertension, and fatigue. Conclusion GEMOX-B could be safely administered with close monitoring and had moderate antitumor activity for patients with advanced HCC. The high 6-month PFS rate is encouraging, and this regimen is worthy of further investigation.

scholarly journals Pembrolizumab as Second-Line Therapy for Advanced Hepatocellular Carcinoma: A Subgroup Analysis of Asian Patients in the Phase 3 KEYNOTE-240 Trial

Liver Cancer ◽  
2021 ◽  
pp. 1-10
Author(s):  
Masatoshi Kudo ◽  
Ho Yeong Lim ◽  
Ann-Lii Cheng ◽  
Yee Chao ◽  
Thomas Yau ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
The Philippines ◽  
Advanced Hepatocellular Carcinoma ◽  
Asian Patients ◽  
Primary Endpoints ◽  
Duration Of Response ◽  
Grade 3

<b><i>Introduction:</i></b> KEYNOTE-240 investigated the efficacy and safety of pembrolizumab plus best supportive care (BSC) in sorafenib-treated patients with advanced hepatocellular carcinoma (HCC). Results for the subgroup of patients from Asia are described. <b><i>Methods:</i></b> Adults with advanced HCC previously treated with sorafenib were randomized 2:1 to pembrolizumab or placebo plus BSC. Here, the Asian subgroup comprised patients enrolled in Hong Kong, Japan, Korea, the Philippines, Taiwan, and Thailand. Primary endpoints were progression-free survival (PFS) per blinded central imaging review and overall survival (OS). Secondary endpoints included objective response rate (ORR) per blinded central imaging review, duration of response (DOR), and safety. <b><i>Results:</i></b> The Asian subgroup included 157 patients. As of January 2, 2019, the median follow-up in this subgroup was 13.8 months for pembrolizumab and 8.3 months for placebo. The median PFS was 2.8 months for pembrolizumab (95% confidence interval [CI] 2.6–4.1) versus 1.4 months (95% CI 1.4–2.4) for placebo (hazard ratio [HR] 0.48; 95% CI 0.32–0.70). The median OS was 13.8 months (95% CI 10.1–16.9) for pembrolizumab versus 8.3 months (95% CI 6.3–11.8) for placebo (HR 0.55; 95% CI 0.37–0.80). ORR was 20.6% (95% CI 13.4–29.5) for pembrolizumab versus 2.0% (95% CI 0.1–10.6) for placebo (difference: 18.5%; 95% CI 8.3–27.6). The median DOR was 8.6 and 2.8 months for pembrolizumab and placebo, respectively. Any grade treatment-related adverse events (TRAEs) occurred in 63 patients (58.9%) receiving pembrolizumab and 24 patients (48.0%) receiving placebo; 14 (13.1%) and 2 (4.0%) patients experienced grade 3–5 TRAEs, respectively. No treatment-related deaths occurred. <b><i>Conclusion:</i></b> Pembrolizumab demonstrated antitumor activity and was well tolerated in the Asian subgroup of KEYNOTE-240. A trend toward greater benefit with pembrolizumab in the Asian subgroup was observed compared with the overall cohort, supporting further evaluation of pembrolizumab treatment in this population.

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

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.

scholarly journals Lenvatinib Plus Immune Checkpoint Inhibitors Improve Survival in Advanced Hepatocellular Carcinoma: A Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaozhun Huang ◽  
Lin Xu ◽  
Teng Ma ◽  
Xin Yin ◽  
Zhangkan Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
New Strategy

BackgroundNivolumab and pembrolizumab disrupt the programmed cell death-1 immune checkpoint and display promising efficacy and safety results in advanced hepatocellular carcinoma (HCC). However, the benefits remain limited. The preliminary results of lenvatinib (LEN) combined with immune checkpoint inhibitors (ICIs) reveal that the combinations were well-tolerated and encouraging. This study aimed to analyze the safety and efficacy of LEN plus ICIs in a real-world cohort of patients with advanced HCC.MethodBetween June 4, 2017, and June 30, 2019, 16 patients received LEN plus nivolumab, and 13 patients were treated with LEN plus pembrolizumab, with the confirmed advanced HCC retrospectively analyzed. The clinical parameters, as well as the outcomes, were assessed.ResultsAll the patients had Barcelona Clinical Liver Cancer Stage C. LEN with ICIs was used as systemic second-, third-, and fourth-line treatments in seven (24.1%), 14 (48.3%), and eight (27.6%) patients, respectively. At the time of data cutoff, six patients (37.5%) were still receiving LEN with nivolumab, while another six patients (46.2%) were still receiving LEN with pembrolizumab. An objective response was recorded in seven patients (25.9%), while the best overall responses were from one complete response and six partial responses. The 6- and 12-month over survival (OS) rates were 62.6% and 53.7%, respectively. Furthermore, the 6- and 12-month progression-free survival (PFS) rates were 43.5% and 31.8%, respectively. In the subgroup analyses, the 6- and 12-month OS and PFS rates for patients treated with LEN plus nivolumab were 62.5% and 52.1%, respectively, and 43.8% and 30.0%, respectively. The 6- and 12-month OS and PFS rates for patients treated with LEN plus pembrolizumab were 51.3% and 51.3%, respectively, and 49.2% and 49.2%, respectively. A total of 11 (31%) deaths were reported in this study, four of which were attributed to grade 5 adverse events presented as fatal treatment-related hepatitis.ConclusionThe combination of LEN and ICIs is a promising new strategy for the treatment of HCC patients. However, high-grade hepatic toxicity was observed and further evaluation of this combination is still required.

scholarly journals Safety of PD-1/PD-L1 Inhibitors Combined With Palliative Radiotherapy and Anti-Angiogenic Therapy in Advanced Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Liting Zhong ◽  
Dehua Wu ◽  
Weiwei Peng ◽  
Hailong Sheng ◽  
Yazhi Xiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Palliative Radiotherapy ◽  
Progression Free Survival ◽  
Treatment Interruption ◽  
Advanced Hepatocellular Carcinoma ◽  
Patient Death ◽  
Angiogenic Therapy ◽  
Grade 3

BackgroundPrevious studies have explored cancer immunotherapy with radiotherapy or anti-angiogenic therapy, but no trials have reported a triple therapy approach. This study aimed to investigate safety and clinical outcome of PD-1/PD-L1 inhibitors combined with palliative radiotherapy and targeted angiogenesis therapy in hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage C.MethodsConsecutive patients (n=16) treated with PD-1/PD-L1 inhibitors combined with radiotherapy and anti-angiogenic therapy in a bi-institutional cohort between July 2017 and December 2020 were retrospectively included. Radiotherapy was conducted within 14 days of the first administration of immunotherapy. The primary endpoint was treatment-related adverse event (TRAE).ResultsThe median follow-up was 383 days. Fifteen patients (93.8%) experienced at least 1 TRAE. The most common TRAEs of any grade were rash (25%), diarrhea (25%), aspartate aminotransferase increase (18.8%), alanine transaminase increase (18.8%), decreased appetite (18.8%), and fatigue (18.8%). Grade 3/4 TRAEs occurred in 4 patients (25%) and finally led to treatment interruption. No patient death was attributed to treatment. No specific events were responsible for the addition of radiotherapy. Six patients showed partial response, 7 showed stable disease, and 2 showed progressive disease. The objective response rate and disease control rate were 40.0% (95% CI 16.3%–67.7%) and 86.7% (95% CI 59.5%–98.3%), respectively. Moreover, the median progression-free survival was 140 days. Patients had a median overall survival of 637 days, and the estimated rates of survival at 6 and 12 months were 92.3% and 75.5%, respectively.ConclusionPD-1/PD-L1 inhibitors combined with palliative radiotherapy and anti-angiogenic therapy appear to be safe, with no unexpected adverse events. Additional studies exploring the clinical benefit are warranted.

Activity of cabozantinib (XL184) in hepatocellular carcinoma: Results from a phase II randomized discontinuation trial (RDT).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4007-4007 ◽  
Author(s):  
Chris Verslype ◽  
Allen Lee Cohn ◽  
Robin Katie Kelley ◽  
Tsai-Shen Yang ◽  
Wu-Chou Su ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Primary Endpoint ◽  
Tumor Regression ◽  
Progression Free Survival ◽  
Median Number ◽  
Advanced Hepatocellular Carcinoma ◽  
Open Label ◽  
Sorafenib Treatment ◽  
Systemic Treatments ◽  
Hep B

4007 Background: Cabozantinib (cabo) is an oral, potent inhibitor of MET and VEGFR2. MET over-expression has been observed in advanced hepatocellular carcinoma (HCC). Anti-VEGF pathway agents have shown clinical benefit in pts w/ HCC. Simultaneous targeting of the MET and VEGF signaling pathways with cabo may therefore be a promising treatment strategy. Methods: Eligible HCC patients (pts) were required to have measurable disease per RECIST, ≤ 1 prior systemic regimen and Child-Pugh score of A. Pts received cabo at 100 mg qd over a 12 wk Lead-in stage. Tumor response (mRECIST) was assessed q6 wks. Treatment ≥ wk 12 was based on response: pts with PR continued open-label cabo, pts with SD were randomized to cabo vs placebo, and pts with PD discontinued. Primary endpoint in the randomized phase was progression free survival (PFS). The primary endpoint was overall response rate (RR) per mRECIST in the Lead-in stage. Results: Enrollment has been completed (n = 41); all pts are unblinded. Median age: 61 years (33 to 83). Males: 76%; Asian: 37%. HCC etiology: Hep B 24%; Hep C 22%; alcohol abuse 20%; other 38%. Extra-hepatic spread observed in 70%. Median number of prior systemic treatments was 1; prior sorafenib was 51%. Median baseline AFP was 368 ng/mL (3 – 259,298); 86% had elevated AFP at baseline. Median follow-up was 5.5 mos (0.8 -18.5). 29 pts (71%) completed the Lead-in stage. Median PFS from Study Day 1 was 4.2 mos. 2/36 pts evaluable for tumor assessment at 12 weeks achieved a confirmed PR (cPR) by original RECIST (RR 5%). One more pt randomized at Week 12 achieved a cPR at 18 weeks. 28/36 pts (78%) with ≥1 post-baseline scan had tumor regression (with no apparent relationship to prior sorafenib therapy). The overall disease control rate (DCR = PR+SD) at Week 12: was 68% (Asian subgroup: 73%). AFP responses (defined as reduction from baseline of >50% in pts with elevated AFP at baseline) in 26 pts with ≥1 post-baseline result: 10/26 (38%). Most common Gr 3/4 AEs: diarrhea (17%), palmar-plantar erythrodyesthesia (15%), and thrombocytopenia (10%). Conclusions: Cabo treatment exhibits activity in HCC pts regardless of prior sorafenib treatment. The safety profile was comparable to that of other VEGFR TKIs.

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