Abstract 944: Analysis of efficacy of receptor tyrosine kinase and immune checkpoint inhibitors and insights to potential combinatorial treatment strategies in cholangiocarcinomas

2021 ◽  
Author(s):  
Jun Liu ◽  
Junning Cao ◽  
Guan Wang ◽  
Bingyang Hu ◽  
Chun Dai ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Combinatorial Treatment

Efficacy of cabozantinib in advanced MiT family translocation renal cell carcinomas (TRCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 274-274
Author(s):  
Jonathan Thouvenin ◽  
Omar Alhalabi ◽  
Laure Hirsch ◽  
Elshad Hasanov ◽  
Philippe Barthelemy ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Receptor Tyrosine Kinase ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitor ◽  
Checkpoint Inhibitors ◽  
Vegf Receptor ◽  
Renal Cell Carcinomas

274 Background: MiT family translocation renal cell carcinomas (TRCC) represent a rare and aggressive subgroup of RCC harboring high expression of c-MET. While response rates of VEGF receptor-tyrosine kinase inhibitor and immune checkpoint inhibitors are limited, efficacy of cabozantinib (a TKI that inhibits VEGFR, MET, and AXL) in this subgroup is unclear. Methods: We performed a multicentre, retrospective, international cohort study of patients with TRCC treated with cabozantinib regardless the line of treatment at 7 centers (3 in France and 4 in the US). The main objectives were to estimate response rate according to RECIST criteria, and to analyze progression-free survival (PFS) and overall survival (OS). Results: Among 31 metastatic patients treated in the participating centers, 24 were evaluable for response and were included in this study (21 with TFE3 and 3 with TFEB translocations). Median age at diagnosis was 43.5 years (range, 22–70). Most frequent metastatic sites at diagnosis were lungs (62.5%), retroperitoneal lymph nodes (45.8%) and bone (37.5%). Patient’s IMDC risk group at diagnosis was favourable (20,8%), intermediate (62,5%) and poor (16,7%). Seven (29%) patients received cabozantinib at first line, 9 (37.5%) at second line and 8 (33%) at third line and beyond. The proportion of patients who achieved an objective response was 16.6%, including 1 complete response and 3 partial responses. For 11 (45.8%) patients, stable disease was the best response. With a median follow-up of 14 months (IQR 5-23), median PFS was 8.4 months (range, 1-34+) and median OS was 17 months (range, 2-43). No PFS difference was detected overall or in any subgroup except in patients with bone metastasis which harbored a median PFS of 3.6 months as compared to 9.1 months for those without (p=0.03). Conclusions: This real-world study provides evidence supporting activity of cabozantinib in TRCC, with more durable responses to therapy than those observed with of VEGF receptor-tyrosine kinase inhibitor and immune checkpoint inhibitors. International collaborations and prospective studies are necessary to identifies efficacious therapies for this rare disease that lacks evidence-based treatment options.

scholarly journals Thrombotic Complications Associated with Immune Checkpoint Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4606
Author(s):  
Tzu-Fei Wang ◽  
Alok A. Khorana ◽  
Marc Carrier
Keyword(s):  
Immune Checkpoint ◽  
Arterial Thrombosis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Relevant Information ◽  
Anticancer Treatment ◽  
Thrombotic Complications ◽  
Associated Risk Factors ◽  
Cancer Associated Thrombosis

Thromboembolism is a common complication in patients with cancer and is associated with significant morbidity and mortality. Anticancer treatment is a known risk factor of cancer-associated thrombosis. Immune checkpoint inhibitors have become a mainstay of treatment in various cancers. Both venous and arterial thrombosis have been increasingly reported as adverse events associated with immune checkpoint inhibitors in recent studies, with a cumulative incidence of venous thrombosis to be 5–8% at 6 months and over 10% at 12 months. Additionally, rates of approximately 1–5% for arterial thrombosis were reported at 12 months. Data also showed an association of thromboembolism with adverse survival. Many pertinent clinical questions in this population deserve further investigation, including the risks of thrombosis associated with immune checkpoint inhibitors as compared to those with traditional systemic therapy, associated risk factors, and the optimal prevention and treatment strategies. In this review, we synthesize data from available literature, provide relevant information for clinicians and potential future directions for research.

Cancer Immunotherapy-Immune Checkpoint Inhibitors in Hepatocellular Carcinoma

2021 ◽  
Vol 16 ◽  
Author(s):  
Jing Bai ◽  
Ping Liang ◽  
Qian Li ◽  
Rui Feng ◽  
Jiang Liu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Locoregional Therapy ◽  
Incidence And Mortality

: Hepatocellular Carcinoma (HCC) is one of the most common malignancies, the incidence and mortality of which are increasing worldwide. Cancer immunotherapy has revolutionized cancer treatment in recent years. In particular, Immune Checkpoint Inhibitors (ICIs) as new therapeutic tools have demonstrated encouraging antitumor activity and manageable tolerability in HCC. Immunologic checkpoint blockade with antibodies targeting Programmed cell Death-1 (PD-1), Programmed cell Death Ligand-1 (PD-L1), and Cytotoxic T Lymphocyte-Associated protein-4 (CTLA-4) strengthens tumor immunity by restoring exhausted T cells. Although the efficacy of combination treatment strategies using ICIs combined with other ICIs, molecular targeted agents, systemic therapy, or locoregional therapy has been well documented in numerous preclinical and clinical studies on several types of cancers, most HCC patients do not benefit from ICI treatment. This review highlights recent developments and potential opportunities related to ICIs and their combination in the management of HCC. The present article also includes recent patent review coverage on this topic.

scholarly journals Transarterial Chemoembolization Improves Survival in Advanced Hepatocellular Carcinoma Patients Treated with Tyrosine Kinase Inhibitors Plus Immune Checkpoint Inhibitors

2021 ◽  
Author(s):  
Yue Hu ◽  
Tao Pan ◽  
Xi Cai ◽  
Quansheng He ◽  
Yubao Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tyrosine Kinase ◽  
Immune Checkpoint ◽  
Transarterial Chemoembolization ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Tace Group

Abstract BackgroundThe survival benefit and safety of transarterial chemoembolization (TACE) for advanced Hepatocellular Carcinoma (HCC) patients treated with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) is unclear. We aimed to investigate the efficacy and safety of TACE combined with TKIs and ICIs the treatment of advanced HCC. MethodsIn this study, the conditions of 147 patients with advanced HCC who underwent TKIs plus ICIs treatment between July 2017 and April 2020 were evaluated. We divided these patients into the TACE group and non-TACE group based on whether they were treated with TACE during TKIs plus ICIs treatment, and compared their survival outcomes, especially overall survival (OS), and whether they were exposed to unexpected toxicities. ResultsIn this study, a total of 98 patients who underwent TACE during TKIs plus ICIs treatment were included in the TACE group, while the other 49 patients were included in the non-TACE group. According to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST), the objective response rate (ORR) of the TACE group was higher than that of the non-TACE group (ORR 74.5% vs. 40.8%, p ＜0.001). The OS of the TACE group was significantly longer than the non-TACE group (OS 19.3 months vs. 10.8 months, p = 0.010). The incidence of grade 3-4 toxicities in the TACE group was similar to that in the non-TACE group (33.7% vs. 28.6%, p = 0.532). ConclusionsThe TACE treatment combined with TKIs plus ICIs resulted in longer OS compared to the treatment of systemic TKIs plus ICIs without TACE during the process of advanced HCC.

Targeted therapies and checkpoint inhibitors in sarcoma

QJM ◽  
2021 ◽  
Author(s):  
M Vasella ◽  
E Gousopoulos ◽  
M Guidi ◽  
G Storti ◽  
S Y Song ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Suppressor Gene ◽  
Treatment Practice ◽  
Therapeutic Concepts

Abstract Sarcomas are defined as a group of mesenchymal malignancies with over 100 heterogeneous subtypes. As a rare and difficult to diagnose entity, micrometastasis is already present at the time of diagnosis in many cases. Current treatment practice of sarcomas consists mainly of surgery, (neo)adjuvant chemo- and/or radiotherapy. Although the past decade has shown that particular genetic abnormalities can promote the development of sarcomas, such as translocations, gain-of-function mutations, amplifications or tumor suppressor gene losses, these insights have not led to established alternative treatment strategies so far. Novel therapeutic concepts with immunotherapy at its forefront have experienced some remarkable success in different solid tumors while their impact in sarcoma remains limited. In this review, the most common immunotherapy strategies in sarcomas, such as immune checkpoint inhibitors, targeted therapy and cytokine therapy are concisely discussed. The programmed cell death (PD)-1/PD-1L axis and apoptosis-inducing cytokines, such as TNF-related apoptosis-inducing ligand (TRAIL), have not yielded the same success like in other solid tumors. However, in certain sarcoma subtypes, e.g. liposarcoma or undifferentiated pleomorphic sarcoma, encouraging results in some cases when employing immune checkpoint inhibitors in combination with other treatment options were found. Moreover, newer strategies such as the targeted therapy against the ancient cytokine macrophage migration inhibitory factor (MIF) may represent an interesting approach worth investigation in the future.

scholarly journals Emerging Novel Therapeutic Approaches for Treatment of Advanced Cutaneous Melanoma

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 271
Author(s):  
Francesca Comito ◽  
Rachele Pagani ◽  
Giada Grilli ◽  
Francesca Sperandi ◽  
Andrea Ardizzoni ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Cutaneous Melanoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Biological Effects ◽  
Adoptive Cell Therapy ◽  
Acquired Resistance ◽  
Treatment Strategies ◽  
Predictive Biomarkers ◽  
Area Of Interest

The prognosis of patients with advanced cutaneous melanoma has radically changed in the past decade. Nevertheless, primary or acquired resistance to systemic treatment occurs in many cases, highlighting the need for novel treatment strategies. This review has the purpose of summarizing the current area of interest for the treatment of metastatic or unresectable advanced cutaneous melanoma, including data from recently completed or ongoing clinical trials. The main fields of investigation include the identification of new immune checkpoint inhibitors (anti-LAG3, GITR agonist and anti-TIGIT), adoptive cell therapy, vaccines, engineered TCR therapy, IL-2 agonists, novel targets for targeted therapy (new MEK or RAF inhibitors, HDAC, IDO, ERK, Axl, ATR and PARP inhibitors), or combination strategies (antiangiogenetic agents plus immune checkpoint inhibitors, intra-tumoral immunotherapy in combination with systemic therapy). In many cases, only preliminary efficacy data from early phase trials are available, which require confirmation in larger patient cohorts. A more in-depth knowledge of the biological effects of the molecules and identifying predictive biomarkers remain crucial for selecting patient populations most likely to benefit from novel emerging treatment strategies.

scholarly journals Safety and Efficacy of Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Hepatocellular Carcinoma

2022 ◽  
Vol 11 ◽  
Author(s):  
Fei Yang ◽  
Jun Yang ◽  
Wei Xiang ◽  
Bin-Yan Zhong ◽  
Wan-Ci Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Immune Checkpoint ◽  
Transarterial Chemoembolization ◽  
Immune Checkpoint Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Safety And Efficacy

PurposeTo explore the safety and efficacy of transarterial chemoembolization (TACE) in combination with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of unresectable hepatocellular carcinoma (uHCC).Materials and MethodsFrom August 2019 to July 2020, patients who received TACE combined with ICIs and TKIs were retrospectively analyzed. Treatment-related adverse events (AEs) were recorded. The Kaplan–Meier method was used to estimate time to progression (TTP) and progression-free survival (PFS).ResultsIn total, 31 patients with uHCC were included. Eleven patients were classified as BCLC-C. Nineteen patients had multiple lesions, and the cumulative targeted lesions were 69 mm (range, 21-170 mm) according to mRECIST. Twenty-nine (93%) patients experienced at least one AE during the treatment. Four (12.9%) patients developed AEs of higher grade (grade≥3). The objective response rate (ORR) and disease control rate (DCR) were 64.5% and 77.4%, respectively. The median time to response was 7 weeks (range, 4-30 w), and the duration of response was 17.5 weeks (range, 2-46 w). From the first ICIs, TTP and PFS were 6.5 months (95% CI, 3.5-11) and 8.5 months (95% CI, 3.5-NE), respectively.ConclusionsTACE combined with ICIs and TKIs shows an acceptable safety profile and considerable efficacy in patients with HCC.

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