scholarly journals Initial Experience of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Real-World Clinical Practice

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2786
Author(s):  
Hideki Iwamoto ◽  
Shigeo Shimose ◽  
Yu Noda ◽  
Tomotake Shirono ◽  
Takashi Niizeki ◽  
...  

Background: Atezolizumab plus bevacizumab was approved for patients with hepatocellular carcinoma (HCC). Although clinical trials have revealed its efficacy, the outcomes in the real-world clinical practice are unclear. We retrospectively evaluated the efficacy and safety of atezolizumab plus bevacizumab for HCC. Materials and Methods: This is a multicenter study conducted between November 2020 and March 2021. Among the 61 patients, 51 were assessed for progression-free survival (PFS), therapeutic response, and adverse events (AEs). Results: The median PFS was 5.4 months. The objective response rate (ORR) was 35.3%. The disease control rate (DCR) was 86.3%. The incidence rates of AEs at any grade and grade >3 were 98.0% and 29.4%, respectively. The most frequent AE at any grade and grade >3 was hepatic disorder. In patients with a previous history of molecular targeted agent (MTA) or the degree of albumin-bilirubin (ALBI) grade, there were no significant differences in the PFS, ORR, DCR, and incidence rates of AEs. Conclusion: The study demonstrated that atezolizumab plus bevacizumab was effective and safe for patients with HCC even in the real-world setting including patients with a previous MTA history or other than ALBI grade 1.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 275-275
Author(s):  
Carla Pires Amaro ◽  
Michael J Allen ◽  
Jennifer J. Knox ◽  
Erica S Tsang ◽  
Howard John Lim ◽  
...  

275 Background: The REFLECT trial establishedlenvatinib (LEN) as a first-line treatment option for hepatocellular carcinoma (HCC). Compared to sorafenib (S), LEN has a higher objective response rate (ORR) and progression-free survival (PFS) with a slightly different toxicity profile. The aim of this study was to gather data regarding the efficacy and safety of LEN when used in the real-world treatment of HCC. To our knowledge, this is the first study to examine LEN use in HCC patients treated outside of Asia. Methods: HCC patients treated with LEN from 10 cancer centers in the Canadian provinces of British Columbia, Alberta, Ontario and Nova Scotia between July 2018 to July 2020 were included. Overall survival (OS), PFS, disease control rate (DCR) and ORR were retrospectively analyzed and compared across first- and second-to-fourth line use of LEN. ORR was determined radiographically according to the treating physician´s opinion in clinical notes and not RECIST 1.1 or mRECIST. Toxicities were also examined. Results: A total of 220 patients were included in this analysis. Median age was 67 years, 80% were men and 25.5% East Asian. The most frequent causes of liver disease were hepatitis C (37%) and B (26%). 62% of patients received any localized treatment before LEN, of those 26% had TACE, 15% TARE and 7.7% had liver transplant. Before starting LEN 29% of patients were ECOG 0 and 59% were ECOG 1. Most patients were Child-Pugh A (81%) and BCLC stage C (75.5%). Main portal vein invasion was present in 14% of the patients. Median follow-up was 4.5 months. A total of 173 patients (79%) received LEN as first line therapy and 47 patients (21%) were treated in second-to-fourth line. Of patients receiving LEN in first line, 22 (13%) started treatment with S, but switched to LEN before progression due to poor tolerance of S. ORR, DCR, PFS and OS are shown in the table. Toxicities occurred in 86% of patients and led to dose reductions in 76 (35%) patients and drug discontinuation in 53 (24%) patients. The most common side effects were fatigue (59%), hypertension (41%), decreased appetite (25%) and diarrhea (22%). Conclusions: Outcomes of HCC patients treated in Canada with LEN in the first line are comparable to those demonstrated in the REFLECT trial, despite the inclusion of Child-Pugh B and ECOG >1 patients. LEN use in second or later lines also showed similar outcomes, although more conclusions are difficult to draw due to the small numbers. LEN appears to be effective and safe in real world practice outside of Asia in first- and second-to-fourth line treatment of HCC. [Table: see text]


Liver Cancer ◽  
2021 ◽  
pp. 1-11
Author(s):  
Myung Ji Goh ◽  
Joo Hyun Oh ◽  
Yewan Park ◽  
Jihye Kim ◽  
Wonseok Kang ◽  
...  

<b><i>Background:</i></b> Lenvatinib has been recently approved as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Korea. We aimed to study the efficacy and safety of lenvatinib therapy in a real-world practice and to find prognostic factors related to survival and disease progression. <b><i>Methods:</i></b> A hospital-based retrospective study was conducted on 111 consecutive patients who had unresectable HCC and were treated with lenvatinib at Samsung Medical Center from October 2018 to March 2020. Efficacy was determined using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria in 111 patients who completed 1st tumor assessment. Safety was evaluated in 116 HCC patients including 5 patients who discontinued lenvatinib due to adverse events (AEs) before 1st tumor assessment using Common Terminology Criteria for AEs version 5.0. <b><i>Results:</i></b> A total of 111 patients with a median age of 59 years were analyzed during a median follow-up duration of 6.2 (4.4–9.0) months. The Kaplan-Meier estimate of overall survival was 10.5 months, and the median progression-free survival was 6.2 months. Based on mRECIST criteria, the objective response rate was 18.9% and disease control rate was 75.7%. AEs developed in 86/116 (74.1%) patients, and grade ≥3 AEs developed in 16/116 (13.8%) patients. Diarrhea, hand-foot skin rash, abdominal pain, hypertension, and anorexia were identified as the AEs with the highest frequencies of any grade. REFLECT eligibility criteria including tumor extent ≥50% liver occupation or inadequate bone marrow function and occurrence of anorexia were prognostic factors for survival, and occurrence of diarrhea was a favorable factor for disease progression. <b><i>Conclusion:</i></b> Lenvatinib therapy showed a favorable efficacy and safety in a real-world practice. The REFLECT eligibility criteria and specific AEs could be one of the prognostic markers.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16138-e16138
Author(s):  
I-Cheng Lee ◽  
Chi-Jung Wu ◽  
San-Chi Chen ◽  
Yee Chao ◽  
Yi-Hsiang Huang

e16138 Background: The combination of lenvatinib (LEN) and pembrolizumab (PEMBRO) showed promising response rates and survival in a phase 1b trial for patients with unresectable hepatocellular carcinoma (HCC). Whether LEN plus PEMBRO provides better outcomes than LEN monotherapy remains unclear. The aim of this study was to compare the outcomes of LEN plus PEMBRO versus lenvatinib monotherapy in patients with unresectable HCC in the real world setting. Methods: A total of 123 patients with unresectable HCC were retrospectively enrolled, including 61 patients with LEN monotherapy and 62 patients with LEN plus PEMBRO. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) by RECIST 1.1 and modified RECIST (mRECIST) criteria. Results: One hundred and one (82.1%) patients were in BCLC stage C and 81 (65.9%) patients received LEN or LEN plus PEMBRO as first line setting. During a median follow-up period of 8.0 months, 71 (57.7%) and 31 (25.2%) of patients had disease progression and death, respectively. The median PFS was 8.4 and 4.9 months in the LEN plus PEMBRO and LEN monotherapy groups, respectively (p = 0.033). The median OS was not reached in the LEN-PEM group and was 17.2 months in the LEN monotherapy group (p = 0.064). Patients with LEN plus PEMBRO had higher objective response rate (ORR: 34.4% vs 23.7% by RECIST 1.1, p = 0.277; 57.4% vs 32.2% by mRECIST, p = 0.010) and higher disease control rate (83.6% vs 62.7% by RECIST 1.1, p = 0.017; 85.2% vs 62.7% by mRECIST, p = 0.009). In subgroup patients with BCLC stage C, LEN plus PEMBRO provided significantly longer PFS (9.1 vs 4.8 months, p = 0.008), higher ORR (60% vs 33.3%, p = 0.015) and higher DCR (88% vs 60.4%, p = 0.004) by mRECIST criteria. Conclusions: LEN plus PEMBRO provides significantly better ORR, DCR and PFS then LEN monotherapy for patients with unresectable HCC.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16192-e16192
Author(s):  
Qicong Mai ◽  
Song Chen ◽  
Feng Shi ◽  
Zhiqiang Mo ◽  
Jian He ◽  
...  

e16192 Background: Lenvatinib has been approved as a first-line systemic for advanced hepatocellular carcinoma (HCC) after the randomized phase III REFLECT trial. The aim of this study was to assess the lenvatinib-base treatment patterns and safety in real-world clinical settings in China. Methods: In this multicenter retrospective study, A total of 278 patients with unresectable HCC were treated with lenvatinib-base treatment between October 2018 and November 2020 were analyzed. Therapeutic effect was determined using the RECIST 1.1 and mRECIST criteria. Progression free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAE) were also evaluated. Results: Of 278 unresectable HCC patients (median age: 56.1±11.9 years), 220 (79.1%) had cirrhosis caused by HBV infection. 215 (77.3%) and 63 (22.7%) patients were classified as Child-pugh A and B class, respectively. 233 (83.8%) and 45 (16.2%) patients received lenvatinib in first-line and second-line systemic therapies, respectively. 223 (80.2%) patients were treated with lenvatinib plus arterially directed therapy (TACE or HAIC of FOLFOX) and 55 (19.8%) were treated with lenvatinib alone. The objective response rate were 34.9% (RECIST) and 47.5% (mRECIST), while the disease control rate were 75.5%. With a median follow-up period of 12.8 months, the median PFS and OS were 7.8 months (95% CI 7.1–8.4) and 17.2 months (95% CI 14.9–19.6), respectively. Results from the multivariate analysis showed that the significant independent favorable prognosis factors were tumor burden< 50% (P=0.033), Child–Pugh A class (P<0.01), AFP level <200ng/mL (P=0.045), the combination with lenvatinib and arterially directed therapy (P<0.01). TRAE occurred in 219 of 278 patients (78.8%), most common TRAE were hypertension (n=118; 42.4%) and hand-foot skin reaction (n=91; 32.7%). The most common grade 3–4 TARE were hypertension (n=23; 8.3%), decreased appetite (n=18; 6.5%), AST elevation (n=14; 5%), and diarrhea (n=14; 5%) across all study patients. Conclusions: In this multicenter real-world study, lenvatinib-base treatment could be accomplished with well tolerated and response for unresectable HCC patients. Combination with arterially directed therapy could likely improve the overall survival.


2021 ◽  
Vol 11 ◽  
Author(s):  
Catherine S. Y. Lecat ◽  
Jessica B. Taube ◽  
William Wilson ◽  
Jonathan Carmichael ◽  
Christopher Parrish ◽  
...  

BackgroundThe treatment paradigm for multiple myeloma (MM) continues to evolve with the development of novel therapies and the earlier adoption of continuous treatments into the treatment pathway. Lenalidomide-refractory patients now represent a challenge with inferior progression free survival (PFS) reported to subsequent treatments. We therefore sought to describe the natural history of MM patients following lenalidomide in the real world.MethodsThis was a retrospective cohort review of patients with relapsed MM who received lenalidomide-based treatments in the U.K. Data were collected for demographics, subsequent therapies, treatment responses, survival outcomes and clinical trial enrollment.Results198 patients received lenalidomide-based treatments at a median of 2 prior lines of therapy at a median of 41 months (range 0.5-210) from diagnosis. 114 patients (72% of 158 evaluable) became refractory to lenalidomide. The overall survival (OS) after lenalidomide failure was 14.7 months having received between 0-6 subsequent lines of therapy. Few deep responses were observed with subsequent treatments and the PFS to each further line was &lt; 7 months. There was a steep reduction in numbers of patients able to receive further treatment, with an associated increase in number of deaths. The OS of patients progressing on lenalidomide who did not enter a clinical trial incorporating novel agents was very poor (8.8 months versus 30 months, p 0.0002), although the trials group were a biologically fitter group.ConclusionThese data demonstrate the poor outcomes of patients failing lenalidomide-based treatments in the real world, the highlight need for more effective treatments.


Author(s):  
Stephen Verderber

The interdisciplinary field of person-environment relations has, from its origins, addressed the transactional relationship between human behavior and the built environment. This body of knowledge has been based upon qualitative and quantitative assessment of phenomena in the “real world.” This knowledge base has been instrumental in advancing the quality of real, physical environments globally at various scales of inquiry and with myriad user/client constituencies. By contrast, scant attention has been devoted to using simulation as a means to examine and represent person-environment transactions and how what is learned can be applied. The present discussion posits that press-competency theory, with related aspects drawn from functionalist-evolutionary theory, can together function to help us learn of how the medium of film can yield further insights to person-environment (P-E) transactions in the real world. Sampling, combined with extemporary behavior setting analysis, provide the basis for this analysis of healthcare settings as expressed throughout the history of cinema. This method can be of significant aid in examining P-E transactions across diverse historical periods, building types and places, healthcare and otherwise, otherwise logistically, geographically, or temporally unattainable in real time and space.


2021 ◽  
Vol 13 ◽  
pp. 175883592110196
Author(s):  
Oliver Illini ◽  
Maximilian Johannes Hochmair ◽  
Hannah Fabikan ◽  
Christoph Weinlinger ◽  
Amanda Tufman ◽  
...  

Introduction: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. Methods: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. Results: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38–89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1–8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53–81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8–22.4) after a median follow-up of 9 months. In patients with measurable brain metastases ( n = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade ⩾ 3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death. Conclusions: In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.


2017 ◽  
Vol 35 (6) ◽  
pp. 611-617 ◽  
Author(s):  
Kazuomi Ueshima ◽  
Naoshi Nishida ◽  
Masatoshi Kudo

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.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P McEwan ◽  
L Hoskin ◽  
K Badora ◽  
D Sugrue ◽  
G James ◽  
...  

Abstract Background Patients with chronic kidney disease (CKD), heart failure (HF), resistant hypertension (RHTN) and diabetes are at an increased risk of hyperkalaemia (HK) which can be potentially life-threatening, as a result of cardiac arrhythmias, cardiac arrest leading to sudden death. In these patients, renin-angiotensin-aldosterone system inhibitors (RAASi), are used to manage several cardiovascular and renal conditions, and are associated with an increased risk of HK. Assessing the burden of HK in real-world clinical practice may concentrate relevant care on those patients most in need, potentially improving patient outcomes and efficiency of the healthcare system. Purpose To assess the burden of HK in a real-world population of UK patients with at least one of: RHTN, Type I or II diabetes, CKD stage 3+, dialysis, HF, or in receipt of a prescription for RAASi. Methods Primary and secondary care data for this retrospective study were obtained from the UK Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES). Eligible patients were identified using READ codes defining the relevant diagnosis, receipt of indication-specific medication, or, in the case of CKD, an estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73m2 within the study period (01 January 2008 to 30 June 2018) or in the five-year lookback period (2003–2007). The index date was defined as 01 January 2008 or first diagnosis of an eligible condition or RAASi prescription, whichever occurred latest. HK was defined as K+ ≥5.0 mmol/L; thresholds of ≥5.5 mmol/L and ≥6.0 mmol/L were explored as sensitivity analyses. Incidence rates of HK were calculated with 95% confidence intervals (CI). Results The total eligible population across all cohorts was 931,460 patients. RHTN was the most prevalent comorbidity (n=317,135; 34.0%) and dialysis the least prevalent (n=4,415; 0.5%). The majority of the eligible population were prescribed RAASi during follow-up (n=754,523; 81.0%). At a K+ threshold of ≥5.0 mmol/L, the dialysis cohort had the highest rate of HK (501.0 events per 1,000 patient-years), followed by HF (490.9), CKD (410.9), diabetes (355.0), RHTN (261.4) and the RAASi cohort (211.2) (Figure 1). This pattern was still observed at alternative threshold definitions of HK. Conclusion This large real-world study of UK patients demonstrates the burden of hyperkalaemia in high-risk patient populations from the UK. There is a need for effective prevention and treatment of HK, particularly in patients with CKD, dialysis or HF where increased incidence rates are observed which in turn will improve patient outcomes and healthcare resource usage. Figure 1. Rates of HK by condition Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 287-287
Author(s):  
Thierry De Baere ◽  
Filipe Veloso Gomes ◽  
Gontran Verset ◽  
Gerardo Tovar-Felice ◽  
Katerina Malagari ◽  
...  

287 Background: Transarterial chemoembolization either with Lipiodol (cTACE) or with drug eluting microspheres (DEM-TACE) is indicated for the treatment of hepatocellular carcinoma (HCC) not amenable to curative treatments in patients with preserved liver function. Safety of TACE is becoming more important with its increased use as a bridge to transplant or downstaging to resection, but also for preservation of liver function in case of subsequent immuno-combination therapies. LifePearl microspheres is a novel DEM comprised of polyethylene-glycol with reported good safety profile and efficacy in smaller series. Our purpose was to assess safety and efficacy of TACE using anthracycline loaded LifePearl for the treatment of patients with unresectable HCC in a pooled analysis of studies with available more than 500 patient’s level data. Methods: We pooled patient level data from 5 single arm studies. Safety was assessed by close monitoring of adverse events according to CTCAE (v4.03). Tumor response was assessed, according to mRECIST and RECIST1.1 and analyzed as best overall response to account for differences in time of imaging follow-up between studies. The Kaplan-Meier method was used to estimate event rates for time to event outcomes: progression free survival (PFS), time to unTACEable progression (TTUP) and overall survival (OS) censoring patients at time of surgery or transplantation. Results: Out of 586 patients, 85.5%, 13.5% and 1.0% were Child Pugh A, B and C, respectively. BCLC stages 0, A, B and C were 13.6%, 43.4%, 41.1% and 1.9% respectively. The mean number of HCC lesions was 2.1±1.5 and mean sum of tumor diameters was 49.3±32.9mm. In 19% of patients alpha-feto protein level was > 200ng/ml. A mean of 1.9±1.3 DEM-TACEs were performed per patient. A total of 197 events were reported including 2.6 % grade 4 and 1.5% grade 5, mostly related to post-embolization syndrome. Complete response, partial response and stable disease were 60.2%, 27.1% and 7.4% respectively providing an objective response and disease control rates of 87,3% and 94,7% respectively. 10% of patients were transplanted or resected. Median OS, PFS and TTUP is indicated in the table below. OS was 89.2%, 80.2% and 69.7% at 12, 18 and 24 months respectively. Conclusions: The treatment of patients with unresectable HCC with anthracycline loaded LifePearl showed good tolerance with acceptable toxicity and high tumor response rate that translated into promising PFS, TTUP and OS. [Table: see text]


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