Target therapies plus somatostatin analogues in NETs: a network meta-analysis

2021 ◽  
Author(s):  
Sara Pusceddu ◽  
Antonio Facciorusso ◽  
Luca Giacomelli ◽  
Natalie Prinzi ◽  
Francesca Corti ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Combination Therapy ◽  
Meta Analysis ◽  
Treatment Options ◽  
Combined Treatment ◽  
Secondary Analysis ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Somatostatin Analogues

Although combination therapy is not recommended in patients with gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs), this strategy is widely used in clinical practice. This network meta-analysis of randomized trials evaluates targeted therapies and somatostatin analogues in GEP advanced NETs, either alone or in combination, comparing the efficacy of different single or combined treatment strategies in terms of progression-free survival (PFS). Interventions were grouped as analogues, everolimus, everolimus plus SSAs, sunitinib and placebo. In a secondary analysis, we also assessed the efficacy of individual specific pharmacological treatments versus placebo or each other. From 83 studies identified, 8 randomized controlled trials were selected, with a total of 1849 patients with either functioning or non-functioning NETs. The analysis confirmed the superiority of all treatments over placebo (HR ranging from 0.34, 95% CI: 0.24–0.37 with the combination of everolimus plus SSAs to 0.42, 0.31–0.57 with the analogues; moderate quality of evidence). On ranking analysis, the combination of everolimus plus SSA (P score=0.86) and then everolimus alone (P score=0.65) ranked highest in increasing PFS. On comparative evaluation of different interventions, pasireotide (P score=0.96) and everolimus+octreotide (P score=0.82) ranked as the best pharmacological treatment options. Our findings support the use of combination therapy in the treatment of functioning and non-functioning GEP NETs. The role of pasireotide should be explored in selected subgroups of patients. Last, the combination of everolimus and octreotide appears promising and should be more widely considered in clinical practice.

scholarly journals Identification and overcoming of resistance to somatostatin analogues in real clinical practice

2017 ◽  
Vol 63 (5) ◽  
pp. 338-345
Author(s):  
Irena A. Ilovayskaya
Keyword(s):  
Clinical Practice ◽  
First Generation ◽  
Tumor Response ◽  
Treatment Options ◽  
Combined Treatment ◽  
Somatostatin Analogues ◽  
Response To Treatment ◽  
Ki 67 ◽  
Genetic Predictors ◽  
Personalized Approach

Resistance to somatostatin analogues (SSAs) is defined as the lack of biochemical and tumor response to the treatment for 12 months. An adequate biochemical response means achieving the target criteria of acromegaly treatment or at least a decrease in the GH and/or IGF-1 levels by >50%. A decrease in the somatotropinoma size by ≥ 20% (when using SSAs as the first line treatment) is considered as the tumor response to treatment. On the basis of treatment efficacy, patients may be classified as non-resistant (biochemical control of acromegaly and tumor response), partially resistant (some degree of biochemical and/or tumor response), and fully resistant (neither biochemical nor tumor response) to SSA therapy. Most patients (up to 60—70%) are partially resistant to the first generation of SSAs. Clinical and biochemical predictors for resistance to SSAs include young age, male gender, high GH/IGF-1 levels, and large invasive sparsely granulated somatotropinoma with high Ki-67 and a hyperintense T2-weighted MRI signal. In recent years, various molecular and genetic predictors for resistance to SSAs have been found; they should be introduced in clinical practice to enable the personalized approach to drug therapy. Treatment options for patients resistant to first-generation SSAs include dose escalation, combined treatment with SSAs and cabergoline, and switching to pasireotide or pegvisomant (not available in Russia); non-drug options include tumor debulking followed by SSA therapy and radiosurgery/radiotherapy.

scholarly journals Systematic Review and network meta-analysis of the efficacy of existing treatments for patients with recurrent glioblastoma (rGBM)

2021 ◽  
Author(s):  
Anna Schritz ◽  
Nassera Aouali ◽  
Aurélie Fischer ◽  
Coralie Dessenne ◽  
Roisin Adams ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Recurrent Glioblastoma ◽  
Comprehensive Overview ◽  
Free Survival ◽  
Treatment Regimens ◽  
Poor Outcomes

Abstract Background Despite advances in the treatment of cancers over the last years, treatment options for patients with recurrent glioblastoma (rGBM) remain limited with poor outcomes. Many regimens have been investigated in clinical trials; however, there is a lack of knowledge on comparative effectiveness. The aim of this systematic review is to provide an overview of existing treatment strategies and to estimate the relative efficacy of these regimens in terms of progression free survival (PFS) and overall survival (OS). Methods We conducted a systematic review to identify randomized controlled trials (RCTs) investigating any treatment regimen in adult patients suffering from rGBM. Connected studies reporting at least one of our primary outcomes were included in a Bayesian network meta-analysis (NMA) estimating relative treatment effects. Results Forty RCTs fulfilled our inclusion criteria evaluating the efficacy of thirty-eight drugs as mono- or combination therapy. Median OS ranged from 2.9 to 18.3 months; median PFS ranged from 0.7 to 6 months. We performed an NMA including 24 treatments that were connected within a large evidence network. Our NMA indicated improvement in PFS with most bevacizumab (BV) based regimens compared to other regimens. We did not find any differences in OS between treatments. Conclusion This systematic review provides a comprehensive overview of existing treatment options for rGBM. The NMA provides relative effects for many of these treatment regimens, which have not been directly compared in RCTs. Overall, outcomes for patients with rGBM remain poor across all treatment options, highlighting the need for innovative treatment options.

scholarly journals Efficacy and Safety of Camrelizumab Monotherapy and Combination Therapy for Cancers: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiting Wang ◽  
Song Su ◽  
Jun Li ◽  
Yaling Li
Keyword(s):  
Combination Therapy ◽  
Meta Analysis ◽  
Combined Treatment ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Endpoints ◽  
Combined Use ◽  
Single Use ◽  
Effectiveness Index ◽  
Better Than

ObjectiveThis meta-analysis compared the safety and efficacy of camrelizumab monotherapy and combination therapy, aiming to provide a reference for the clinical combined use of camrelizumab in the treatment of cancers and also provide a reference for the development of subsequent indications of camrelizumab.MethodsMeta-analysis was used to analyze the four eligible literatures. Primary endpoints of effectiveness index were objective response rate (ORR), progression-free survival (PFS), control rate (CR). Primary endpoint of safety index was rating of severity of adverse drug reactions (grades 1–5).ResultsThe ORR, PFS, and CR values of combined treatment with camrelizumab was better than alone treatment, camrelizumab alone was better than chemotherapy (RR = 0.45; 95% CI, 0.30–0.67; P < 0.001; RR = 1.63; 95% CI, 1.25–2.13; P < 0.001; RR = 0.73; 95% CI, 0.52–1.02; P<0.001). When grade > 2, the incidence rate of combined treatment and chemotherapy are higher than monotherapy (RR = 0.66; 95% CI, 0.51–0.86; P<0.001). In any grade, the safety of camrelizumab combination therapy was better than that of monotherapy, the safety of chemotherapy was better than camrelizumab plus chemotherapy.ConclusionIn terms of effectiveness, the combination of camrelizumab is better than monotherapy, and monotherapy is better than chemotherapy. In terms of safety, when the grade > 2, single use is better than combination therapy and chemotherapy. In any grade of adverse event, the safety of combined use of camrelizumab is better than that of single use, and the safety of chemotherapy is better than the combined use of camrelizumab plus chemotherapy.

scholarly journals B Cells and Antibodies as Targets of Therapeutic Intervention in Neuromyelitis Optica Spectrum Disorders

2021 ◽  
Vol 14 (1) ◽  
pp. 37
Author(s):  
Jan Traub ◽  
Leila Husseini ◽  
Martin S. Weber
Keyword(s):  
B Cells ◽  
Neuromyelitis Optica ◽  
Plasma Cells ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Complement Factor ◽  
Major Subset ◽  
Spectrum Disorders

The first description of neuromyelitis optica by Eugène Devic and Fernand Gault dates back to the 19th century, but only the discovery of aquaporin-4 autoantibodies in a major subset of affected patients in 2004 led to a fundamentally revised disease concept: Neuromyelits optica spectrum disorders (NMOSD) are now considered autoantibody-mediated autoimmune diseases, bringing the pivotal pathogenetic role of B cells and plasma cells into focus. Not long ago, there was no approved medication for this deleterious disease and off-label therapies were the only treatment options for affected patients. Within the last years, there has been a tremendous development of novel therapies with diverse treatment strategies: immunosuppression, B cell depletion, complement factor antagonism and interleukin-6 receptor blockage were shown to be effective and promising therapeutic interventions. This has led to the long-expected official approval of eculizumab in 2019 and inebilizumab in 2020. In this article, we review current pathogenetic concepts in NMOSD with a focus on the role of B cells and autoantibodies as major contributors to the propagation of these diseases. Lastly, by highlighting promising experimental and future treatment options, we aim to round up the current state of knowledge on the therapeutic arsenal in NMOSD.

scholarly journals Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 304
Author(s):  
Marta Araujo-Castro ◽  
Eider Pascual-Corrales ◽  
Javier Molina-Cerrillo ◽  
Teresa Alonso-Gordoa
Keyword(s):  
Adrenocortical Carcinoma ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Mechanisms Of Resistance ◽  
Response Efficacy ◽  
Predictors Of Response ◽  
Primary Endpoints ◽  
Tumor Mutational Burden

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options in the advanced stages. Immunotherapy offers hope for altering the orthodox management of cancer, and its role in advanced ACC has been investigated in different studies. With the aim clarifying the role of immunotherapy in ACC we performed a comprehensive review about this topic focusing on the predictors of response, efficacy, safety, and the mechanisms of resistance. Five clinical trials with four immune checkpoint inhibitors (pembrolizumab, avelumab, nivolumab, and ipilimumab) have investigated the role of immunotherapy in advanced ACC. Despite, the different primary endpoints used in these studies, the reported rates of overall response rate and progression free survival were generally poor. Three main potential markers of response to immunotherapy in ACC have been described: Expression of PD-1 and PD-L1, microsatellite instability and tumor mutational burden. However, none of them has been validated in prospective studies. Several mechanisms of ACC immunoevasion may be responsible of immunotherapy failure, and a greater knowledge of these mechanisms might lead to the development of new strategies to overcome the immunotherapy resistance. In conclusion, although currently the role of immunotherapy is limited, the identification of immunological markers of response and the implementation of strategies to avoid immunotherapy resistance could improve the efficacy of this therapy.

scholarly journals Tumor Microenvironment: Key Players in Triple Negative Breast Cancer Immunomodulation

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3357
Author(s):  
Hongmei Zheng ◽  
Sumit Siddharth ◽  
Sheetal Parida ◽  
Xinhong Wu ◽  
Dipali Sharma
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Treatment Options ◽  
Combined Treatment ◽  
High Mobility ◽  
Sphingosine 1 Phosphate ◽  
Molecular Patterns

Triple negative breast cancer (TNBC) is a heterogeneous disease and is highly related to immunomodulation. As we know, the most effective approach to treat TNBC so far is still chemotherapy. Chemotherapy can induce immunogenic cell death, release of damage-associated molecular patterns (DAMPs), and tumor microenvironment (TME) remodeling; therefore, it will be interesting to investigate the relationship between chemotherapy-induced TME changes and TNBC immunomodulation. In this review, we focus on the immunosuppressive and immunoreactive role of TME in TNBC immunomodulation and the contribution of TME constituents to TNBC subtype classification. Further, we also discuss the role of chemotherapy-induced TME remodeling in modulating TNBC immune response and tumor progression with emphasis on DAMPs-associated molecules including high mobility group box1 (HMGB1), exosomes, and sphingosine-1-phosphate receptor 1 (S1PR1), which may provide us with new clues to explore effective combined treatment options for TNBC.

scholarly journals Effectiveness comparisons of various therapies for FIGO stage IB2/IIA2 cervical cancer: a Bayesian network meta-analysis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Cheng ◽  
Beibei Liu ◽  
Biao Wang ◽  
Xicui Long ◽  
Zhihong Li ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Bayesian Network ◽  
Cancer Patients ◽  
Radical Surgery ◽  
Meta Analysis ◽  
Treatment Options ◽  
Female Genital Tract ◽  
Treatment Strategies ◽  
Final Analysis ◽  
Phase Iii

Abstract Background Cervical cancer is a common malignancy of the female genital tract. Treatment options for cervical cancer patients diagnosed at FIGO (2009) stage IB2 and IIA2 remains controversial. Methods We perform a Bayesian network meta-analysis to directly or indirectly compare various interventions for FIGO (2009) IB2 and IIA2 disease, in order to improve our understand of the optimal treatment strategy for these women. Three databases were searched for articles published between 1971 and 2020. Data on included study characteristics, outcomes, and risk of bias were abstracted by two reviewers. Results Seven thousand four hundred eighty-six articles were identified. Thirteen randomized controlled trials of FIGO (2009) IB2 and IIA2 cervical cancer patients were included in the final analysis. These trials used six different interventions: concomitant chemoradiotherapy (CCRT), radical surgery (RS), radical surgery following chemoradiotherapy (CCRT+RS), neoadjuvant chemotherapy followed by radical surgery (NACT+RS), adjuvant radiotherapy followed by Radical surgery (RT + RS), radiotherapy alone (RT).SUCRA ranking of OS and Relapse identified CCRT+RS and CCRT as the best interventions, respectively. Systematic clustering analysis identified the CCRT group as a unique cluster. Conclusion These data suggest that CCRT may be the best approach for improving the clinical outcome of cervical cancer patients diagnosed at FIGO (2009) stage IB2/IIA2. Phase III randomized trials should be performed in order to robustly assess the relative efficacy of available treatment strategies in this disease context.

Combining Cognitive-Behavioral Therapy and Pharmacotherapy for the Treatment of Panic Disorder

2006 ◽  
Vol 20 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Jasper A. J. Smits ◽  
Conall M. O’Cleirigh ◽  
Michael W. Otto
Keyword(s):  
Panic Disorder ◽  
Combination Treatment ◽  
Behavioral Therapy ◽  
Combined Treatment ◽  
Treatment Strategies ◽  
Cognitive Behavior ◽  
Short Term ◽  
Medication Treatment ◽  
Novel Approaches

This article focuses on the role of combination treatment strategies in the management of panic disorder (PD). Despite short-term benefits, there is not consistent evidence for a longer-term advantage of combined treatment over cognitive-behavior therapy alone. In discussing this result, we place emphasis on ways in which medication treatment may interfere with the learning of safety in relation to feared cues in PD. These considerations are placed in the context of animal and human studies of factors that interfere with the extinction of fears. Strategies to overcome this interference are also discussed as are novel approaches to combination treatment.

scholarly journals Prognostic Role of High Stathmin 1 Expression in Patients with Solid Tumors: Evidence from a Meta-Analysis

2018 ◽  
Vol 50 (1) ◽  
pp. 66-78 ◽  
Author(s):  
Qingyan Mao ◽  
Zhen Chen ◽  
Kun Wang ◽  
Renfang Xu ◽  
Hao Lu ◽  
...  
Keyword(s):  
English Literature ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Online Databases ◽  
Stathmin 1 ◽  
Tumor Types ◽  
Disease Free

Background/Aims: Several recent studies have demonstrated that Stathmin 1expression may be closely associated with prognosis in patients with various types of cancers. In the present study, we conducted a meta-analysis of all available studies in the English literature to assess the prognostic value of Stathmin 1expression in patients with solid cancers. Methods: The online databases PubMed, Embase, and Web of Science were searched for literature regarding Stathmin 1 and its association with patient outcomes associated with solid cancers. Results: A total of 23 articles including 26 studies that contained 5 335 patients were retrieved and analyzed. Our results indicated that high Stathmin 1 expression yielded a worse overall survival (OS) (hazard ratio [HR] = 2.17, 95% confidence interval [CI]: 1.81–2.60), disease-free survival (DFS) (HR = 2.46, 95% CI: 2.00–3.02), disease-specific survival (DSS) (HR = 1.98, 95% CI: 1.58– 2.47) and progression-free survival (PFS)/recurrence-free survival (RFS) (HR = 2.09, 95% CI: 1.51–2.89). Furthermore, the association of high Stathmin 1 expression with poor survival was significant even for sub-group analyses of different tumor types, ethnicities, methods used to calculate HRs, detected methods, and analysis types. Conclusion: In summary, this meta-analysis determined that high Stathmin 1 expression is associated with poor prognosis in patients with solid cancers and expression of this protein could be a clinically useful prognostic biomarker.

[177Lu]Lu-DOTA-TATE Versus Standard of Care in Adult Patients With Gastro-Enteropancreatic Neuroendocrine Tumours (GEP-NETS): A Cost-Consequence Analysis From an Italian Hospital Perspective

2021 ◽  
Author(s):  
Francesca Spada ◽  
Davide Campana ◽  
Giuseppe Lamberti ◽  
Riccardo Laudicella ◽  
Renato Dellamano ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Neuroendocrine Tumours ◽  
Treatment Options ◽  
Treatment Decision ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Somatostatin Analogues ◽  
Adult Patients ◽  
Hospital Perspective ◽  
Cost Consequence

Abstract Purpose To assess and compare clinical outcomes and costs, to the Italian healthcare system, of three therapeutic options approved in the management of adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs). Methods We compared the efficacy, safety and costs of [177Lu]Lu-DOTA-TATE, everolimus (both originator and generic products) and sunitinib in patients with advanced GEP-NETs (NET G1 and G2) that had progressed following treatment with somatostatin analogues (SSAs). A cost-consequence model was developed and validated by a panel of clinical experts from three NET reference centres in Italy. The clinical outcomes included in the model were median progression-free survival and the incidence of grade 3 or 4 adverse events (AEs), as reported in pivotal clinical trials. The costs for acquisition and administration of each treatment, and of managing AEs, were calculated from the perspective of the Italian national health service. Treatment costs per progression-free month were calculated separately for patients with NETs of pancreatic (PanNETs; all three treatments) and gastrointestinal (GI-NETs; [177Lu]Lu-DOTA-TATE and everolimus only) origin. Results In patients with PanNETs, total costs per progression-free month were €2989 for [177Lu]Lu-DOTA-TATE, €4975 for originator everolimus, €3472 for generic everolimus, and €5337 for sunitinib. In patients with GI-NETs, total costs per progression-free month were €3189 for [177Lu]Lu-DOTA-TATE, €4990 for originator everolimus, and €3483 for generic everolimus. Conclusions [177Lu]Lu-DOTA-TATE was associated with lower costs per progression-free month versus relevant treatment options in patients with GI-NETs or PanNETs (NET G1–G2; progressed following SSA treatment), although acquisition and administration costs are higher. These findings provide further economic arguments in the overall context of treatment decision making.

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