scholarly journals Complete Response Associated With Combination Treatment Regorafenib and Sintilimab in a Sorafenib-refractory Hepatocellular Carcinoma Patient

2020 ◽  
Author(s):  
Erlei Zhang ◽  
Zunyi Zhang ◽  
Lei Zhang ◽  
Shuai Xiang ◽  
Xiaoping Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Resection ◽  
Combination Therapy ◽  
Disease Progression ◽  
Combination Treatment ◽  
Lung Metastases ◽  
Complete Response ◽  
Advanced Hcc ◽  
Liver Recurrence ◽  
Short Period

Abstract Background Most of patients diagnosed with Hepatocellular carcinoma (HCC) have advanced diseases and many are not eligible for curative therapies. There is a growing evidence suggesting that combination treatment of PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors (TKIs) becomes a prospective trend for advanced HCC. For those HCC patients with sorafenib resistance, the efficacy of regorafenib combined with PD-1/PD-L1 inhibitors remains unclear. Case presentation: Herein, we represent a case of HCC with lung metastasis in the setting of HBV-induced liver cirrhosis responding dramatically to the combination treatment of sorafenib-regorafenib sequential and PD-1 inhibitor after initial liver resection. A 56-year-old man diagnosed with AFP-negative HCC underwent liver resection in September 2015, and was found to have solitary liver recurrence and lung metastases in March 2017. He received microwave coagulation therapy and trans-arterial chemoembolization (TACE) for liver tumor and treatment was started with sorafenib 400 mg twice daily for controlling lung metastases. In December 2018, abdominal computerized tomography (CT) scan showed two new lesions in liver. In March 2019, disease progression of lung metastases was measured and he received 160 mg regorafenib once daily. After a short period of partial response, he started treatment with regorafenib 160 mg in combination with sintilimab (200 mg, 3 weeks as a cycle) in December 2019 due to disease progression. Surprisingly, after 5 cycles of sintilimab injection, it showed complete response in target lesions. There is no clinical evidence of disease progression and the side effects were mild and well tolerated. The current overall survival is 57 months. Conclusion Data from this clinical case report suggests that combination therapy of regorafenib and PD-1 inhibitor is a promising therapeutic option for the treatment of advanced HCC. This is the first article reporting the complete response to regorafenib combination therapy with PD-1inhibitor for sorafenib-regractory HCC.

Triple combination therapy comprising angiogenesis inhibitors, anti-PD-1 antibodies, and hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16124-e16124
Author(s):  
Ti Zhang ◽  
Jinliang Zhang ◽  
Xihao Zhang ◽  
Han Mu ◽  
Ge Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Hepatic Arterial Infusion ◽  
Angiogenesis Inhibitors ◽  
Triple Combination ◽  
Arterial Infusion ◽  
Triple Combination Therapy ◽  
Arterial Infusion Chemotherapy ◽  
Advanced Hcc ◽  
Infusion Chemotherapy

e16124 Background: The effects of single-drug therapy for the systemic treatment of advanced unresectable hepatocellular carcinoma (HCC) remain unsatisfactory, promoting the emergence of multi-drug and combination therapies. Here we assess the safety and efficacy of a triple combination therapy for treating advanced HCC. Methods: This single-center retrospective study included patients with unresectable HCC treated with triple combination therapy comprising angiogenesis inhibitors (oral apatinib 250 mg/day, lenvatinib 8 mg/day, or sorafenib 400 mg BID), anti-programmed cell death 1 antibodies (iv camrelizumab or sintilimab, 200 mg every 3 weeks), and hepatic arterial infusion chemotherapy (FOLFOX every 4–8 weeks). Eligible patients had completed at least one cycle of therapy and had an imaging assessment. Treatment-related adverse events (TRAEs) were assessed according to the Common Terminology Criteria for Adverse Events. Efficacy data were summarized according to modified RECIST (mRECIST) and RECIST v1.1. Results: Of 34 patients who received triple combination therapy, 25 (19 men and 6 women; median age: 59 years [range: 49–78]) had an imaging assessment. TRAEs were manageable; 28.0% of patients experienced grade 3–4 TRAEs. Efficacy outcomes are summarized in the Table. The objective response rate was 96.0% (mRECIST), the median time to response was 50.5 days (95% CI: 31.02–64.00) and the surgical conversion rate was 56%, indicating a robust therapeutic effect. Overall, 12 patients (48.0%) achieved a complete response (CR), 12 (48.0%) achieved a partial response, and one (4.0%) had stable disease (mRECIST). Fourteen patients (56.0%) underwent surgical resection, after which seven (28.0%) achieved a pathologic CR. After a median follow-up of 9.67 months, no cases of post-operative recurrence or metastasis emerged. Conclusions: Triple combination therapy had a robust therapeutic effect with a high surgical conversion rate in patients with advanced HCC. TRAEs were acceptable, and long-term efficacy is reasonably expected. Summary of efficacy outcomes (n = 25).[Table: see text]

scholarly journals Hypothyroidism Is a Predictive Factor for Better Clinical Outcomes in Patients with Advanced Hepatocellular Carcinoma Undergoing Lenvatinib Therapy

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3078
Author(s):  
Masako Shomura ◽  
Haruka Okabe ◽  
Emi Sato ◽  
Kota Fukai ◽  
Koichi Shiraishi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Duration ◽  
Hormone Replacement ◽  
Evaluation Criteria ◽  
Complete Response ◽  
Good Prognosis ◽  
Advanced Hepatocellular Carcinoma ◽  
Thyroid Hormone Replacement ◽  
Advanced Hcc ◽  
Therapy Initiation

Patients with advanced hepatocellular carcinoma (HCC) undergoing molecular targeted therapy often experience non-negligible adverse events (AEs). Paradoxically, certain AEs are reportedly associated with a good prognosis. We aimed to identify factors predictive of treatment duration and overall survival (OS) in patients with HCC undergoing lenvatinib therapy. Forty-six consecutive patients with advanced HCC who received lenvatinib therapy from April 2018 to November 2019 were prospectively followed until November 2019. Treatment efficacy was assessed according to the modified Response Evaluation Criteria in Solid Tumors for 2–3 months after therapy initiation. The disease control rate (DCR) was defined as the percentage of patients with a complete response, partial response, or stable disease. The DCR was 65.2%, with a median survival of 10.2 months. Grade 2/3 hypoalbuminemia resulted in shorter treatment duration. Factors predictive of longer OS were a Child-Pugh score of 5 at baseline and the occurrence of Grade 2/3 hypothyroidism. Conversely, Grade 2/3 hypoalbuminemia was associated with a poorer prognosis. An AE of Grade 2/3 hypothyroidism was associated with a better prognosis in patients receiving lenvatinib treatment for advanced HCC. Continuing anticancer therapy with appropriate thyroid hormone replacement may contribute to longer OS.

Complete Response of Advanced Hepatocellular Carcinoma with Multiple Lung Metastases Treated with Sorafenib: A Case Report

Oncology ◽  
2011 ◽  
Vol 81 (s1) ◽  
pp. 152-157 ◽  
Author(s):  
Tadashi Inuzuka ◽  
Hiroki Nishikawa ◽  
Akira Sekikawa ◽  
Haruhiko Takeda ◽  
Shinichiro Henmi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Case Report ◽  
Lung Metastases ◽  
Complete Response ◽  
Advanced Hepatocellular Carcinoma

scholarly journals Tumor Lysis Syndrome after Combination Therapy of Nivolumab and Sorafenib in a Woman with Advanced Hepatocellular Carcinoma

2020 ◽  
Vol 14 (2) ◽  
pp. 367-372 ◽  
Author(s):  
Tsai-Hung Yen ◽  
Chung-Hsin Chang ◽  
Sz-Iuan  Shiu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Tumor Lysis Syndrome ◽  
Tumor Burden ◽  
Therapeutic Interventions ◽  
Advanced Hepatocellular Carcinoma ◽  
Large Tumor ◽  
Tumor Lysis ◽  
Advanced Hcc ◽  
First Case

Tumor lysis syndrome (TLS) is a life-threatening emergency that usually develops in rapidly proliferating hematologic malignancies or advanced solid tumor following cytotoxic chemotherapy or therapeutic interventions. TLS is especially rare in patients with hepatocellular carcinoma (HCC). Therefore, we present a case of a female patient with newly diagnosed advanced HCC who developed TLS and hepatic failure after receiving combination therapy of nivolumab and sorafenib. To our knowledge, this is the first case of TLS in a patient with advanced HCC owing to combination therapy of nivolumab and sorafenib. We also reviewed the literature and summarized the characteristics of TLS in patients with advanced HCC receiving various therapeutic interventions. The overall mortality rate was 63% and regarding the management, transarterial chemoembolization (TACE) was the most common etiology. TACE-related TLS developed more rapidly than sorafenib-related TLS. Furthermore, the efficacy and safety of combination therapy of nivolumab and sorafenib should be further evaluated, and TLS should still be a concern, especially in patients with large tumor burden.

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

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4087-4087 ◽  
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.

Phase Ib/II study of sorafenib (SOR) and pembrolizumab (PEM) in advanced hepatocellular cancer (HCC).

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS596-TPS596 ◽  
Author(s):  
Rohit Gosain ◽  
Sarbajit Mukherjee ◽  
Sunyoung S. Lee ◽  
Austin Miller ◽  
Hans Minderman ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Combination Treatment ◽  
Hepatocellular Cancer ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Fixed Dose ◽  
Serum Total Bilirubin ◽  
Advanced Hcc ◽  
Pre Treatment ◽  
Ecog Ps

TPS596 Background: SOR has been the backbone of advanced HCC therapy with poor outcome. Anti-PD-1 therapy is approved as a second-line treatment option in HCC due to its promising efficacy and safety. Our preclinical work showed that SOR is immunomodulatory and may be synergistic when combined with anti-PD-1 therapy. Guided by this data, we initiated this multicenter study of SOR and PEM in advanced HCC patients (pts). Methods: Pts who have Child-Pugh Class A, ECOG PS of 0/1, biopsy-proven measurable HCC that is unresectable or metastatic, are included. Pts must not receive either SOR or anti-PD-1 therapy before. A total of 27 pts will be enrolled from 2 sites. Pts must have the following lab values: ANC ≥ 1,500/ mc; Hgb ≥ 8.5 g/dL; Plts ≥75,000/ mcL; serum total bilirubin ≤ 2.0 mg/dL; AST/ALT ≤ 5 X ULN; serum creatinine ≤ 1.5 X ULN. Pts with active hep B must be on antiviral therapy. Pts would be on a 4-week run-in of SOR alone at 400mg BID to ensure tolerability and stable dose (minimum 200 BID) before beginning PEM 200mg IV q3 weeks. Both drugs would be administered until progression or unacceptable toxicity with response assessment q6 weeks by RECIST 1.1 criteria. Primary endpoint: response rate. Secondary endpoints: safety, overall survival, and progression-free survival. Correlative Endpoints: Pre-treatment levels of immunosuppressive cells and the functional activity of effector T cells would be compared to post-treatment blood and tumor samples. The first 6 pts who completed 4 weeks of SOR-only treatment and began the combination therapy (addition of PEM at a fixed dose of 200 mg Q3W) would comprise the safety lead-in. Pts who withdrew before initiation of combination therapy (for reasons other than DLT) would be replaced. Dose-Limiting toxicity was defined as any ≥ grade 3 clinically significant toxicity, which is deemed possibly treatment-related and occurs within the first cycle of combination therapy. Toxicity would be assessed by NCI CTCAEV4.0. Status: First patient enrollment on 12/19/2017. On 11/28/2018, our 6th patient completed the SOR lead-in phase and began combination treatment with SOR and PEM. As of Sept 12, 2019, thirteen pts have enrolled, and 9 pts have received combination treatment. Support: Merck. Clinical trial information: NCT03211416.

scholarly journals Combination of Sorafenib, Camrelizumab, Transcatheter Arterial Chemoembolization, and Stereotactic Body Radiation Therapy as a Novel Downstaging Strategy in Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombus: A Case Series Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Yun Huang ◽  
Zeyu Zhang ◽  
Weijun Liao ◽  
Kuan Hu ◽  
Zhiming Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Adverse Events ◽  
Tumor Thrombus ◽  
Stereotactic Body Radiation Therapy ◽  
Transcatheter Arterial Chemoembolization ◽  
Case Series ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Arterial Chemoembolization

Background and AimAlthough the treatment effect and availability of therapeutic options for advanced hepatocellular carcinoma (HCC) are limited, the downstaging strategy may improve patient prognosis. This study aimed to investigate the potential of combination therapy as a downstaging strategy for treating advanced HCC with portal vein tumor thrombus (PVTT).MethodsThis retrospective case series included patients having advanced HCC with PVTT, who received the combination therapy of sorafenib, camrelizumab, transcatheter arterial chemoembolization (TACE), and stereotactic body radiation therapy (SBRT) from January 2019 to December 2019 in Xiangya Hospital, Central South University. The downstaging rate, treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated.ResultsOf the 13 patients, HCC downstaging was achieved in 4 (33.3%) patients who later received hepatectomy. The overall response rate was 41.7%, and the disease control rate was 50.0%. The median PFS time was 15.7 months, with a 1-year PFS rate of 58.3%, whereas the median OS was not reached after 1 year (1-year OS, 83.3%). No severe adverse events or grade 3–4 adverse effect was observed in 12 of the 13 enrolled patients; therapy had to be discontinued in only one patient due to adverse events, who was excluded from the study. The most common adverse effect was fever (n = 4, 33.3%), followed by skin reaction (n = 3, 25%).ConclusionA combination therapy comprising sorafenib, camrelizumab, TACE, and SBRT is an effective downstaging strategy for advanced HCC with PVTT and is associated with few adverse events.

scholarly journals Phase I studies of peptide vaccine cocktails derived from GPC3, WDRPUH and NEIL3 for advanced hepatocellular carcinoma

Immunotherapy ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 371-385
Author(s):  
Masafumi Ikeda ◽  
Takuji Okusaka ◽  
Izumi Ohno ◽  
Shuichi Mitsunaga ◽  
Shunsuke Kondo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase I ◽  
Peptide Vaccine ◽  
Complete Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Two Phase ◽  
Good Tolerability ◽  
Clinical Trial Registration ◽  
Phase I Studies ◽  
Advanced Hcc

Aim: Two peptide cocktail vaccines using glypican-3, WD-repeat-containing protein up-regulated in hepatocellular carcinoma (HCC) and nei endonuclease VIII-like three epitopes were evaluated in advanced HCC in two Phase I studies. Patients & methods: Study 1 evaluated dose-limiting toxicities (DLTs) of peptides 1–3 (HLA-A24-restricted) and study 2 evaluated DLTs of peptides 1–6 (HLA-A24 or A02-restricted). Results: Overall, 18 and 14 patients were enrolled in studies 1 and 2, respectively. No DLTs were observed up to 7.1 mg of the vaccine cocktail. No complete response/partial response was observed. Stable disease was reported in nine and five patients with a disease control rate of 52.9% and 35.7% in studies 1 and 2, respectively. Conclusion: Both vaccines showed good tolerability and potential usefulness against HCC. Clinical trial registration: JapicCTI-121933 ; JapicCTI-142477

Complete response of early stage hepatocellular carcinoma in a patient treated with combination therapy of camrelizumab (SHR-1210) and apatinib

2019 ◽  
Vol 51 (10) ◽  
pp. 1488-1490 ◽  
Author(s):  
Zeyu Zhang ◽  
Yufan Zhou ◽  
Kuan Hu ◽  
Zhecheng Li ◽  
Zhiming Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Early Stage ◽  
Complete Response

Response of advanced HCC to pembrolizumab and lenvatinib combination therapy despite monotherapy failure

2020 ◽  
Vol 58 (08) ◽  
pp. 773-777 ◽  
Author(s):  
Nadine Schulte ◽  
Moying Li ◽  
Tianzuo Zhan ◽  
Lena Dreikhausen ◽  
Janina Sollors ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Combination Therapy ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
The World ◽  
Vegf Inhibition ◽  
Tki Treatment

AbstractIn recent years, immune checkpoint inhibitors (ICIs) were successfully introduced to cancer therapy, and these drugs have already become essential for the treatment of various noncurable tumors. However, monotherapy in advanced hepatocellular carcinoma (aHCC) failed to show statistically significant improvement.Recently, the combination of atezolizumab and bevacizumab demonstrated efficacy of combining ICI and VEGF inhibition, further substantiating previous data on synergistic mechanisms among respective substance classes.As TKI treatment is currently standard of care for aHCC, and ICIs are approved by the FDA and available in many areas of the world, numerous patients may have been treated with monotherapy of those drugs. However, it remains unclear if failure to monotherapy has an impact on combination therapy. We therefore report a patient well responding to combination therapy despite previous failures to TKI and ICI monotherapy.

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