Real-world treatment characteristics for first-line therapy (1L) of advanced hepatocellular carcinoma (HCC) in Canada and Europe.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 353-353
Author(s):  
Sharlene Gill ◽  
Dena H Jaffe ◽  
Marc DeCongelio ◽  
Arnold N. DuBell ◽  
Jing Shi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Function ◽  
Portal Vein ◽  
Real World ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Unmet Need ◽  
Advanced Hepatocellular Carcinoma ◽  
Portal Vein Invasion

353 Background: Sorafenib is indicated for the treatment of HCC. This study captures and describes real-world use of 1L therapy for advanced unresectable or metastatic HCC across Canada and Europe. Methods: A retrospective, non-interventional survey of 278 physicians in Canada (7.5%) and Europe (92.5%) (France, Germany, Italy, Spain and UK) was conducted between Feb-Mar 2018. Clinical and treatment data were collected from medical charts for patients aged ≥18y, who initiated and completed systemic 1L treatment for HCC within 2 years of data collection, and a Child-Pugh [CP] A/B at 1L initiation. Descriptive statistics compared 1L systemic therapy, sorafenib vs. other. Results: 706 patients were included (n = 504 sorafenib; n = 202 other [83% chemotherapy; 10% targeted therapy; 7% checkpoint inhibitors]) with a mean age at 1L of 62.7±9.3y and 79% males. Comorbidities did not differ by sorafenib vs. other for alcoholism (33%), Hepatitis C (14%), and nonalcoholic steatohepatitis and/or nonalcoholic fatty liver disease (9%) but did for Hepatitis B (12% vs. 6%) and cirrhosis (31% vs. 18%) (both p < 0.05). At diagnosis, more patients treated with sorafenib vs. other had portal vein invasion (56% vs. 35%, p < 0.001). At 1L initiation, sorafenib patients had better performance status (PS) (ECOG 0-1: 80% vs. 67%, p < 0.05) and preserved liver function (CP A: 58% vs. 47%, p < 0.05). The results indicated that sorafenib was used less compared to other systemic therapies among those with poor performance (ECOG 2-4) and poor liver function (CP B) (71% vs. 83%, p = 0.068). Median treatment duration was shorter for sorafenib (2 vs. 4 months, p < 0.001). The most common grade 3 adverse events were fatigue (9%), diarrhea (5%), and hand/foot skin reaction (4%). Conclusions: In this real-world chart survey of Canadian and European physicians, sorafenib remains the most commonly used 1L systemic therapy for advanced HCC. Patients treated with sorafenib were more likely to have cirrhotic liver disease, portal vein invasion, better PS and preserved liver function, but sorafenib use was not limited to CP A. Understanding determinants of 1L therapy is important as the treatment landscape of HCC is evolving to address unmet need.

Use of sorafenib in recurrent hepatocellular carcinoma (HCC) after liver transplantation.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 440-440
Author(s):  
Joanne Wing-Yan Chiu ◽  
Thomas Cheung Yau ◽  
Tan To Cheung ◽  
Albert Chan ◽  
Siu-Ho Chok ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Function ◽  
Median Time ◽  
Systemic Therapy ◽  
Graft Rejection ◽  
Standard Dose ◽  
Performance Status ◽  
Unmet Need ◽  
Duration Of Treatment ◽  
Ecog Performance Status

440 Background: Sorafenib (Sor) is the only approved systemic therapy for advanced HCC yet the safety and efficacy for its use in patients (pts) who developed recurrence after liver transplantation (LT) has not been established. There is an unmet need for treatment option in this group of pts. Methods: This is a retrospective analysis of pts treated with Sor for recurrent HCC post-LT in Queen Mary Hospital, Hong Kong. Results: During year Jan 2008 to Feb 2014, 25 post-LT pts with HCC recurrence were treated with Sor. Tacrolimus and sirolimus were the immunosuppressant of choice during the same treatment period in 76% (19/25) and 40% (10/25) pts respectively. All pts had Child-Pugh A liver function and ECOG performance status 0-1. Majority of pts were chronic hepatitis B carriers (88%) and male (88%). Median time to recurrence was 13.2 months (range 3.4-71.1). Intrahepatic recurrence and extrahepatic recurrence were found in 52% and 80% of pts respectively. Up to 68% of pts received the standard dose of 800 mg/day. The most common adverse events (AEs) were hand-foot syndrome (44%) and diarrhea (28%). G3 transaminase elevation was found in 4 pts (16%), in which 2 had histological evidence of acute graft rejection. Both cases were associated with tailing down of tacrolimus upon tumor progression, and the liver function recovered after adjustment of immunosuppressant. Nine pts (36%) required dose adjustment. The median maintenance dose was 400 mg/day. The median duration of treatment was 4.44 months (95% CI 2.53-6.44). Median time to progression was 6.21 months (95% CI 2.83-9.63). Median overall survival was 13.6 months (95% CI 7.69-19.61). Ten (40%) pts also received other subsequent systemic therapy. Conclusions: Sor given in combination with tacrolimus and sirolimus did not lead to unexpected graft rejection. The drug is in general tolerated in this population and toxicities appeared to be similar to non-transplant pts. Further study is required to evaluate for drug interaction and efficacy.

scholarly journals Controlling Major Portal Vein Invasion Progression during Lenvatinib Treatment by Carbon-Ion Radiotherapy in Patients with Advanced Hepatocellular Carcinoma

2021 ◽  
pp. 1103-1110
Author(s):  
Ryoi Yoshida ◽  
Keisuke Koroki ◽  
Hirokazu Makishima ◽  
Sadahisa Ogasawara ◽  
Takamasa Ishino ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Portal Vein ◽  
Systemic Therapy ◽  
Standard Treatment ◽  
Carbon Ion Radiotherapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Portal Vein Invasion ◽  
Main Trunk ◽  
Advanced Hcc ◽  
Carbon Ion

Macrovascular invasion (MVI), including portal vein tumor thrombosis (PVTT), is strongly associated with poor prognosis in patients with hepatocellular carcinoma (HCC). While recommended standard treatment for patients with advanced HCC is systemic therapy, various treatment approaches, including resection, transarterial chemoembolization, and radiation, have been empirically suggested to improve prognosis by eliminating or controlling MVI. Herein, we report our experience of a case with advanced HCC where MVI was controlled by carbon-ion radiotherapy (CIRT) while on systemic therapy, resulting in a prolonged survival. A female patient with HCC in her early 60s had multiple intrahepatic lesions (maximum 60 mm in diameter) with PVTT. The PVTT of this patient had reached the main trunk of the portal vein despite the use of lenvatinib. The other intrahepatic lesions of the patient, except PVTT, had been controlled by lenvatinib. Therefore, hoping to control PVTT, we attempted CIRT. The patient resumed lenvatinib therapy after the irradiation. During lenvatinib re-treatment, no evident progression of PVTT was observed in the patient.

scholarly journals Effectiveness and Safety of Immune Checkpoint Inhibitors for Patients with Advanced Non Small-Cell Lung Cancer in Real-World: Review and Meta-Analysis

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1388
Author(s):  
Manlio Mencoboni ◽  
Marcello Ceppi ◽  
Marco Bruzzone ◽  
Paola Taveggia ◽  
Alessia Cavo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Group Performance ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Small Cell ◽  
Small Cell Lung ◽  
Eligibility Criteria

Immunotherapy based on anti PD-1/PD-L1 inhibitors is the new standard of advanced non-small cell lung cancers. Pembrolizumab, nivolumab and atezolizumab are used in clinical practice. The strict eligibility criteria of clinical trials do not allow researchers to fully represent treatment effects in the patients that will ultimately use these drugs. We performed a systematic review and a meta-analysis to evaluate the effectiveness and safety of these drugs, and more generally of ICIs, as second-line therapy in NSCLC patients in real world practice. MEDLINE, PubMed, Scopus and Web of Science were searched to include original studies published between January 2015 and April 2020. A total of 32 studies was included in the meta-analysis. The overall radiological response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and overall survival (OS) were 21%, 52%, 3.35 months and 9.98 months, respectively. The results did not change when analysis was adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS) and age. A unitary increase in the percent of patients with liver and CNS metastases reduced the occurrence of DCR by 7% (p < 0.001) and the median PFS by 2% (p = 0.010), respectively. The meta-analysis showed that the efficacy and safety of immunotherapy in everyday practice is comparable to that in clinical trials.

Unresectable hepatocellular carcinoma: prospects for drug therapy with lenvatinib

2022 ◽  
Vol 11 (3) ◽  
pp. 45-52
Author(s):  
V.  V. Breder ◽  
D.  T. Abdurakhmanov ◽  
V.  V. Petkau ◽  
P.  V. Balakhnin ◽  
M.  V. Volkonsky ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Therapy ◽  
Liver Function ◽  
Real World ◽  
Systemic Therapy ◽  
Efficacy And Safety ◽  
Study Results ◽  
Class B ◽  
Pugh Class ◽  
Positive Results

There is a number of unresolved issues regarding the systemic therapy administration for hepatocellular carcinoma (HCC). Their solution is facilitated by accumulating real‑world study results. Lenvatinib therapy is a recognized drug with a good efficacy and safety profile for the treatment of HCC. Subanalyses of the REFLECT study showed that the absence of stratification by baseline AFP and baseline liver function, as well as the lack of options for subsequent drug therapy after lenvatinib, also affects the outcomes. Once these factors are taken into account, the hypothesis of superiority of lenvatinib to sorafenib and other drugs can be tested. Real‑world clinical studies have demonstrated positive results of lenvatinib therapy in patients with Child‑Pugh class B liver function, provided recommendations on the sequence of systemic therapy after lenvatinib and on the use of lenvatinib in patients with BCLC stage B, along with considering the possibility of lenvatinib monotherapy and the prospects for its use in patients with nHCC. Further real‑world studies of lenvatinib for HCC in the Russian population are required.

Treatment patterns among patients with advanced urothelial carcinoma following discontinuation of PD1/L1 inhibitor therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 414-414
Author(s):  
Alicia K. Morgans ◽  
Simrun Kaur Grewal ◽  
Zsolt Hepp ◽  
Rupali Fuldeore ◽  
Shardul Odak ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Real World ◽  
Chart Review ◽  
Group Performance ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group ◽  
Unmet Need ◽  
Case Series ◽  
Treatment Patterns

414 Background: There are a lack of published real-world data on treatment patterns for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) previously treated with programmed death 1/ligand 1 inhibitor (PD-1/L1i) therapy. The objective of this study was to characterize the clinical characteristics and treatments among patients with la/mUC following discontinuation of first-line (1L) or second-line (2L) PD-1/L1i therapy. Methods: We performed a retrospective chart review at 26 geographically diverse clinical sites in the US. Patients aged ≥18 years with histologically or cytologically confirmed urothelial carcinoma and radiographic evidence of metastatic or locally advanced disease were identified. Included patients had initiated and subsequently discontinued PD-1/L1i therapy in the 1L or 2L setting for la/mUC between May 15, 2016-July 31, 2018. All patients had follow-up through October 31, 2019. Data were summarized using descriptive statistics. Results: Among the 300 patients included in the chart review, 198 (66%) received PD-1/L1i therapy as 1L and 102 (34%) as 2L therapy. Mean (SD) age at la/mUC diagnosis was 69.4 (8.7) years, and a majority of patients were male (66.0%) and White (74.7%). Consistent with age, most patients (82.7%) had comorbidities at la/mUC diagnosis; 39.7% hypertension, 23.7% coronary artery disease, 17.7% pulmonary disease, and 9.3% renal disease. At initiation of therapy, a higher proportion of patients who received 1L PD-1/L1i therapy had an Eastern Cooperative Oncology Group performance status of 2 or more than patients who received 2L PD-1/L1i therapy (36.8% vs 22.5%, respectively). Following discontinuation of PD-1/L1i therapy, 34% (n = 68) received subsequent therapy in 2L and 29% (n = 30) in third-line (3L). The most common subsequent therapies in 2L were gemcitabine monotherapy (24%), gemcitabine plus cisplatin or carboplatin (22%), PD-1/L1i therapy (22%), and taxane monotherapy (19%). The most common subsequent therapies received in 3L were taxane monotherapy (50%), pemetrexed (17%), and PD-1/L1i therapy (16%). Overall, switching from one PD-1/L1i therapy to another distinct PD-1/L1i therapy occurred in approximately 20% of patients, with “better efficacy/survival” noted by treatment teams as the most common reason for switching therapy among this subgroup. Conclusions: In this real-world case series, only a minority of patients with la/mUC who discontinued PD-1/L1i therapy received subsequent therapy. Among those that did, no clear standard of care was observed and approximately one-fifth of patients were treated with a second PD-1/L1i therapy after the first failed to control disease. Collectively, the data highlight significant unmet need for patients with la/mUC who discontinue PD-1/L1i therapy.

Radioembolization in Advanced Hepatocellular Carcinoma

2018 ◽  
Vol 36 (19) ◽  
pp. 1898-1901 ◽  
Author(s):  
Ahsun Riaz ◽  
Robert Lewandowski ◽  
Riad Salem
Keyword(s):  
Hepatocellular Carcinoma ◽  
Portal Vein ◽  
Group Performance ◽  
Performance Status ◽  
Relevant Literature ◽  
Eastern Cooperative Oncology Group ◽  
Distant Metastases ◽  
Advanced Hepatocellular Carcinoma ◽  
Vein Thrombosis ◽  
Management Approaches

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 68-year-old man with a remote history of alcohol abuse presented with vague abdominal pain. A review of systems suggested the patient had an Eastern Cooperative Oncology Group performance status 1 (restriction of strenuous physical activity). There were no physical examination findings of note. Laboratory studies disclosed Child-Pugh A liver status (no ascites; no encephalopathy; total bilirubin, 1 mg/dL; albumin, 3.5 g/dL; and international normalized rato, 1.2). The alpha-fetoprotein was mildly elevated (19.5 ng/mL). Magnetic resonance imaging with contrast disclosed an infiltrative mass with extensive malignant right and left portal vein thrombosis ( Fig 1A ) with cavernous transformation of the portal vein. The infiltrative mass ( Fig 2A ) was biopsied, revealing hepatocellular carcinoma. No distant metastases were found on a bone scintigraphy or computerized tomography scan. Given these features, this patient was classified as Barcelona Clinic for Liver Cancer stage C. The patient was referred for management of advanced hepatocellular carcinoma.

scholarly journals Real-World Efficacy and Safety of Lenvatinib in Korean Patients with Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis

Liver Cancer ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 613-624 ◽  
Author(s):  
Jaekyung Cheon ◽  
Hong Jae Chon ◽  
Yeonghak Bang ◽  
Neung Hwa Park ◽  
Jung Woo Shin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Analysis ◽  
Real World ◽  
Checkpoint Inhibitors ◽  
Clinical Trial Data ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
First Line

Introduction/Objective: Lenvatinib demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the randomized phase III REFLECT trial. Considering the discrepancies in patients between clinical trial data and daily practice, an account of practical experience is needed. Methods: We conducted a multicenter retrospective analysis in which 3 tertiary referral centers participated. A total of 92 patients with advanced HCC treated with lenvatinib between September 2018 and January 2020 were analyzed. Results: Lenvatinib was used as the first-line therapy for 67 (72.8%) patients, and for 25 (27.2%) patients previously treated with other systemic therapy including immune checkpoint inhibitors. At the time of initiation of lenvatinib, 74 (80.4%) and 18 (19.6%) patients were classified as Child-Pugh A and B, respectively. Thirty-five patients (38.0%) had extensive disease that would have excluded them from the REFLECT trial. In the Child-Pugh A group, the response rate graded according to the Response Evaluation Criteria in Solid Tumors v1.1 was 21.1%, median progression-free survival (PFS) was 4.6 (95% confidence interval [CI] 3.1–6.1) months, and overall survival (OS) was 10.7 (95% CI 4.8–16.5) months for patients treated with first-line lenvatinib (n = 57). With second- or later-line lenvatinib (n = 17), median PFS and OS were 4.1 (95% CI 3.1–5.1) and 6.4 (95% CI 5.1–7.7) months, respectively. In the Child-Pugh B group (n = 18), median PFS and OS were 2.6 (95% CI 0.6–4.6) and 5.3 (95% CI 2.0–8.5) months, respectively. The most common grade 3–4 toxicities were hyperbilirubinemia (n = 8; 8.7%), AST elevation (n = 6; 6.5%), and diarrhea (n = 5; 5.4%) across all study patients. Conclusions: In this real-world study, lenvatinib was found to be well tolerated and effective in more heterogeneous HCC patient populations.

scholarly journals CMET-23. IMPACT OF SYSTEMIC THERAPY IN MELANOMA BRAIN METASTASIS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi56-vi56
Author(s):  
Soumya Sagar ◽  
Adam Lauko ◽  
Addison Barnett ◽  
Wei (Auston) Wei ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Checkpoint Inhibitors ◽  
Care Center ◽  
Performance Status ◽  
Tertiary Care ◽  
P Value ◽  
Surgical Removal

Abstract BACKGROUND Melanoma is the third most common malignancy that results in brain metastasis and is associated with a median overall survival (OS) of approximately 9 months. In recent years, management of melanoma brain metastases (MBM) by surgery and radiation [stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT)] has been bolstered by targeted therapy and immune checkpoint inhibitors (ICI). METHODS 351 patients, treated for MBM at our tertiary care center from 2000–2018, were grouped into: received chemotherapy, ICI, or targeted therapy. 34% of patients treated with ICI had received other systemic therapies as well as part of their management. OS was calculated from the date of diagnosis of the brain metastases. The Kaplan Meier analysis was utilized to determine median OS and difference in OS was determined by utilizing the Cox proportional hazard model. RESULTS The median survival after the diagnosis of brain metastasis was 10.4, 11.96, and 7.06 months in patients who received ICI, chemotherapy and targeted therapy respectively. A multivariate model was developed including the type of systemic therapy, presence of extracranial metastases, age, KPS and number of intracranial lesions. 114 patients underwent SRS alone, 56 underwent SRS and WBRT, 43 underwent SRS and surgical removal, 28 had surgical removal, SRS and WBRT, and 78 had no intracranial therapy. Compared to patients who received chemotherapy, patients who received immunotherapy had a hazard ratio, HR = 0.628 (confidence interval = 0.396 – 0.994, p-value = 0.047). Presence of EC metastases (HR= 1.25, p-value < .001), lower KPS (HR = .97, p-value < .0001) and multiple brain lesions (HR = 1.117, p-value < .0001) were associated with significantly worse OS. CONCLUSIONS Addition of ICI significantly improves the OS in MBM compared to chemotherapy. Lower performance status, multiple brain metastases, and EC metastases are associated with poor OS.

Assessment of radioembolization among patients who met the inclusion criteria for Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14654-e14654 ◽  
Author(s):  
Bruno Sangro ◽  
Livio Carpanese ◽  
Roberto Cianni ◽  
Daniele Gasparini ◽  
Rita Golfieri ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Function ◽  
Median Overall Survival ◽  
Performance Status ◽  
Advanced Hepatocellular Carcinoma ◽  
Inclusion Criteria ◽  
Ecog Performance Status ◽  
Advanced Hcc ◽  
Good Liver Function

e14654 Background: SHARP was pivotal in determining the safety and efficacy of sorafenib in advanced hepatocellular carcinoma (HCC) in patients with predominately good liver function. In practice, many patients with advanced HCC receive radioembolization (RE). Investigators from the European Network on RE with yttrium-90 resin microspheres (ENRY) group conducted an analysis of safety and survival among consecutive patients who met the SHARP inclusion criteria. Methods: 58% of patients (189 of 325) who had received RE between 09/2003 and 12/2009 were considered SHARP-equivalents. Of these, 11.6% received sorafenib 4.7 months (median) after RE for a median duration of 2.8 months. Safety and tolerability analyses were conducted up to day 90 post RE; changes from baseline were recorded and transitions in CTCAE grades >3 tested. Statistical analyses used SAS (SAS, Cary NC) version 9.2 XP Pro. Results: Like the SHARP sorafenib cohort, most patients had advanced HCC (BCLC stage C: 72.5%), good liver function (Child–Pugh class A: 100%) and ECOG performance status (0–1: 90.5%). Macroscopic vascular invasion (MVI), extrahepatic spread (EHD) or both was present in 33.9%. 20.1% had received prior surgical procedures, 8.5% prior ablative procedures and 33.3% prior vascular [chemo]embolization. RE was predominantly a single whole-liver procedure (median activity 1.7 GBq). Median overall survival was 10.8 months (95% CI: 8.8–12.8) in the SHARP-equivalent cohort, 10.2 months (8.3–11.8) in patients with MVI/EHD, 9.7 months (7.6–10.9) in advanced HCC (BCLC stage C) and 16.6 months (11.2–22.8) in intermediate HCC (BCLC stage B). Treatment-related adverse events (all grades; grade >3) were: fatigue (50.3%; 2.1%), abdominal pain (25.9%; 2.1%), nausea/vomiting (31.2%; 0.5%) and GI ulcer (3.2%; 1.0%). At baseline, raised bilirubin (all grades) was present in 20.3%, increasing to 49.4% of patients evaluated up to day 90. Bilirubin grade was unchanged in 58.1% and increased in 37.8%; 4.0% had ≥grade 3 events. Conclusions: In patients matching the inclusion criteria for SHARP, RE was well tolerated with a median overall survival which compares favorably with sorafenib.

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