scholarly journals What if Bevacizumab was discontinued! Can IMpower130 be exchanged for IMpower150 for advanced non-squamous NSCLC patients with PD-L1 <50% and without genomic mutations?

2021 ◽  
Vol 11 (2) ◽  
pp. 291-297
Author(s):  
Khaled Elmahdi Omran
Keyword(s):  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Chemotherapeutic Agents ◽  
Significant Difference ◽  
Nsclc Patients ◽  
The Impact

There was a radical change in the first-line management of advanced NSCLC with negative genetic oncological drive in the last 5 years. Immune checkpoint inhibition is currently recommended for such a group of patients by major international guidelines devoted to lung cancer, as long as there is no contraindication. The recommendations came as a single agent of immune checkpoint inhibitor, combination of an immune checkpoint inhibitor with chemotherapy with an optional anti-angiogenic agent, or combination between two different immune checkpoint inhibitors; based on the level of expression of programmed death-ligand 1 in the tumour microenvironment and the type of immune checkpoint inhibitor is intended to be used. IMpower150 was a clinical trial that illustrated the effectiveness of the addition of Atezolizumab (immune checkpoint inhibitor) to chemotherapy and Bevacizumab (anti-angiogenic agent) in treatment naïve advanced non-squamous NSCLC patients with no genetic aberrations. In the same trial, there was no significant difference between chemotherapy plus either Atezolizumab or Bevacizumab. Moreover, Atezolizumab experienced other disappointing results in different clinical trials in NSCLC and other malignancies such as triple-negative breast cancer when combined with chemotherapeutic agents that require corticosteroids as pre-medications during therapy. This review evaluates the synergistic anti-neoplastic effect of immune checkpoint inhibitor and anti-angiogenic agent in NSCLC which presented in IMpower150 by Atezolizumab and Bevacizumab, especially this combination is the preferred option for other malignancies such as hepatocellular carcinoma and renal cell carcinoma. Additionally, the review overlooks the impact of corticosteroids on Atezolizumab in different clinical trials, particularly in NSCLC.

scholarly journals 466 Use of a 27-gene immuno-oncology (IO) assay to associate response to single-agent immune checkpoint inhibitor (ICI) therapy in advanced-stage NSCLC patients from a large Canadian cohort

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A495-A495
Author(s):  
David Saltman ◽  
Nicole Croteau ◽  
Heather Lockyer ◽  
Rob Seitz ◽  
Frank McMahon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Retrospective Study ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Single Agent ◽  
Research Project ◽  
Vice Chair ◽  
Nsclc Patients

BackgroundLung cancer is the leading cause of cancer-related deaths worldwide. The advent of ICIs specifically targeting programmed cell death protein-1 (PD-1), or its ligand (PD-L1) represents a major therapeutic advance that is now included in standard of care regimens for non-small-cell-lung cancer (NSCLC). PD-L1 expression measured by immunohistochemistry (IHC) staining is the current gold standard predictive biomarker for immune checkpoint inhibitor (ICI) therapy in NSCLC, however many factors beyond PD-L1 expression alone affect the outcome of ICI therapy. Evaluation of other factors to better inform clinical practice will reduce both the potential for adverse immune-related toxicities and expenditure on ineffective costly therapies while potentially identifying patients otherwise missed by PD-L1 staining. The 27-gene IO assay is a RT-qPCR based gene expression panel1 that was developed to classify the tumor immune microenvironment (TIME). It has been shown to be associated with response to ICI therapy in multiple tumor types including triple negative breast cancer, metastatic urothelial carcinoma, and NSCLC where the association was independent of PD-L1 status in patients treated either with monotherapy or combination therapy.2 Currently, BC Cancer measures PD-L1 status by IHC using the PD-L1 22C3 PharmDx assay and reports the tumor proportional score (TPS) to inform clinical decision. Patients with a TPS ≥ 50% may be eligible for first-line treatment with ICI monotherapy and those with < 50% TPS are eligible for second line or later ICI monotherapy. We established this retrospective study of ICI monotherapy treated NSCLC patients to assess the 27-gene IO assay as an informative biomarker for NSCLC ICI treatment decisions.MethodsThis retrospective study is utilizing the BC Cancer Study Database to select approximately 150 patients with stage IIIB or IV NSCLC treated with single-agent ICI therapy across four BC Cancer centers from 2017 forward (figure 1). Patients are selected based on availability of adequate biopsy specimens (FFPE with at least 20% tumor content), availability of PD-L1 IHC results or sufficient tissue to conduct staining, and for whom outcome data is available via chart review. RNA from patient samples is isolated from FFPE biopsies (either primary or metastatic sites) and those that yield ≥50ng RNA will be analyzed by the 27-gene IO assay 1 to derive IO scores (IO positive or IO negative) based on previously defined thresholds.3 The association between patient outcomes on ICI monotherapy and IO scores and PD-L1 IHC will be reported and compared.Abstract 466 Figure 1Schematic representation of patient workflow forReferencesSaltman, A, et al. Prostate cancer biomarkers and multiparametric MRI: is there a role for both in prostate cancer management? Ther Adv Urol 2021;13: 1756287221997186.Ranganath HJA, Smith JR, et al. One-year progression-free survival in lung cancer patients treated with immune checkpoint inhibitors is significantly associated with a novel immunomodulatory signature but not PD-L1 staining. in SITC. Journal Immunotherapy Cancer. 2019.Nielsen, TJ, et al. A novel immuno-oncology algorithm measuring tumor microenvironment to predict response to immunotherapies. Heliyon 2021;7(3):e06438.Ethics ApprovalThe University of British Columba BC Cancer Research Ethics Board Chair, Vice-Chair or second Vice-Chair, has reviewed the above described research project, including associated documentation, and finds the research project acceptable on ethical grounds for research involving human subjects. All participants have provided informed consent before taking part in the study. REB Number H20-02635.

Venous thromboembolism events in patients with advanced cancer on immune checkpoint inhibitors

Immunotherapy ◽  
2021 ◽  
Author(s):  
Adi Kartolo ◽  
Cynthia Yeung ◽  
Gordon T Moffat ◽  
Lilian Hanna ◽  
Wilma Hopman ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Advanced Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Cancer Management ◽  
Thromboembolism Events

Aim: To evaluate the correlation between venous thromboembolism events (VTEs) and immune checkpoint inhibitor (ICI)-based regimens. Methods: This is a retrospective study of 403 patients with advanced cancer on ICI-based regimens. Results: We report 8% VTE incidence post-ICI initiation over a median of 11.1 months of follow-up. Compared with single-agent ICI, dual-ICI was significantly correlated with higher incidence of VTE (odds ratio [OR]: 4.196, 95% CI: 1.527–11.529, p = 0.005), but chemotherapy–immuno-oncology combination was not (OR: 1.374, 95% CI: 0.285–6.632, p = 0.693). Subsequent systemic therapy post-ICI was also independently associated with higher VTE incidence (OR: 2.599, 95% CI: 1.169–5.777, p = 0.019). Conclusion: Our findings suggest potential underreporting of VTE incidence in ICI clinical trials. As dual-ICI is becoming more prevalent in cancer management, clinicians should maintain vigilance regarding VTE in patients with advanced cancer on ICI-based regimens.

scholarly journals Immune checkpoint inhibitor use, multimorbidity and healthcare expenditures among older adults with late-stage melanoma

Immunotherapy ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 103-112
Author(s):  
Pragya Rai ◽  
Chan Shen ◽  
Joanna Kolodney ◽  
Kimberly M Kelly ◽  
Virginia G Scott ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Late Stage ◽  
Mixed Models ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Excess Cost ◽  
Healthcare Expenditures ◽  
Adjusted Model ◽  
The Impact

Background: The objective of this study is to assess the impact of immune checkpoint inhibitors (ICIs) and multimorbidity on healthcare expenditures among older patients with late-stage melanoma. Materials & methods: A retrospective longitudinal cohort study using Surveillance, Epidemiology and End Results linked with Medicare claims was conducted. Generalized linear mixed models were used to analyze adjusted relationships of ICI, multimorbidity and ICI–multimorbidity interaction on average healthcare expenditures. Results: Patients who received ICI and those who had multimorbidity had significantly higher average total healthcare expenditures compared with ICI nonusers and no multimorbidity. In the fully adjusted model using ICI–multimorbidity interaction, no excess cost was added by multimorbidity. Conclusion: Use of ICIs, regardless of multimorbidity, is associated with increased healthcare expenditures.

Impact of pharmacist-managed immune checkpoint inhibitor toxicities

2020 ◽  
pp. 107815522092840
Author(s):  
Sonny Le ◽  
Brandon Chang ◽  
Anthony Pham ◽  
Andrea Chan
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Hormone Replacement ◽  
Retrospective Chart Review ◽  
Physician Satisfaction ◽  
Pharmacist Interventions ◽  
Oral Corticosteroids ◽  
The Impact

Background Immune checkpoint inhibitors are associated with unique autoimmune side effects that differ from traditional cytotoxic chemotherapy. Pharmacists may play an important role in providing key supportive care measures necessary to aid patients and oncologists through immune-related adverse events (irAEs). This study aims to evaluate the impact of a pharmacist-managed irAE protocol in an oncology clinic. Methods This study is a retrospective chart review of the implementation of a pilot irAE pharmacy protocol. Patients treated with an immune checkpoint inhibitor and subsequently identified to have dermatologic, gastrointestinal, hepatic, or thyroid toxicities and managed under the pilot irAE pharmacy protocol from 1 October 2018 to 28 February 2019 were enrolled. Study endpoints included number of pharmacist interventions and physician satisfaction. Additional endpoints included pharmacotherapy initiated, dose adjustments, and patient follow-ups. Results From 1 October 2018, to 28 February 2019, 17 patients were referred and approved by their primary oncologists for pharmacy management under the pilot irAE protocol. During the pilot period, pharmacists initiated 21 new medications for the treatment of irAEs, including thyroid hormone replacement in 7 patients (41%) and oral corticosteroids in 6 patients (35%) with a total of 28 dose adjustments. In addition, the pilot protocol included an assessment of physician satisfaction, which showed a reduced number of physician hours per month managing irAEs, increased physician confidence in irAE management, and a desire for continued pharmacist-management of irAEs. Conclusions Oncology pharmacists had an impact on management of toxicities in our oncology clinic as indicated by the pharmacist interventions and physician satisfaction.

scholarly journals Efficacy and safety of immune checkpoint inhibitors in colorectal cancer: a systematic review and meta-analysis

2021 ◽  
Author(s):  
Tianni Zeng ◽  
Xiaojie Fang ◽  
Jinhua Lu ◽  
Yazhen Zhong ◽  
Xianlei Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Therapy Group ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Significant Difference ◽  
Colorectal Cancer Patients

Abstract Background and objective Immune checkpoint inhibitor (ICI) therapies have shown promising prospects in colorectal cancer (CRC) immunotherapy; many clinical trials have been carried out. In this study, we sought to evaluate the efficacy and safety of ICI therapies in CRC by presenting a meta-analysis of relevant studies. Methods Databases including PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for studies concerning the efficacy and safety of ICI in colorectal cancer. The reported odds ratio (OR) or weighted mean difference (WMD) with 95% confidence intervals (CIs) of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), treatment-related adverse events (TRAEs), and TRAEs ≥ 3 in the included studies were analyzed by fixed effects/random effects models. Results Three studies involving 667 patients with colorectal cancer were included in our meta-analysis. No significant difference between the immune checkpoint inhibitor therapies and conventional therapies in OS (WMD = 0.73, 95% CI − 3.09, 4.54; p = 0.71), in ORR (OR = 1.54, 95% CI 0.98, 2.40; p = 0.06), and in DCR (OR = 0.97, 95% CI 0.36, 2.61; p = 0.95). The median PFS of the ICI therapy group was shorter than that of the conventional therapy group (WMD =  − 0.10, 95% CI − 0.18, − 0.02; p = 0.02). At the same time, we also could not find a significant difference between the immune checkpoint inhibitor therapies and conventional therapies in TRAEs (OR = 1.56, 95% CI 0.11, 22.09; p = 0.74) and in TRAEs ≥ 3 (OR = 0.94, 95% CI 0.16, 5.65; p = 0.95). Conclusion Immune checkpoint inhibitor therapies could not improve all survival endpoints to advanced or metastatic colorectal cancer patients. Whether immune checkpoint inhibitors should be the first choice of therapies for colorectal cancer patients with undetermined microsatellite status or not able to determine microsatellite status needs more related studies to prove.

scholarly journals Immunotherapy for Advanced Non–Small Cell Lung Cancer: A Decade of Progress

2021 ◽  
pp. 1-23
Author(s):  
Misty Dawn Shields ◽  
Julian A. Marin-Acevedo ◽  
Bruna Pellini
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Single Agent ◽  
Chemotherapeutic Agents ◽  
Small Cell ◽  
Small Cell Lung

The treatment paradigm for patients with advanced non–small cell lung cancer has substantially changed with the discovery of immunotherapy. The incorporation of immunotherapy into treatment algorithms has resulted in better outcomes for patients, with fewer side effects compared with classic chemotherapeutic agents. Multiple treatment options are now available for patients with advanced non–small cell lung cancer, ranging from single-agent immunotherapy to quadruple therapy, which involves dual immune checkpoint inhibitor plus chemotherapy or immune checkpoint inhibitor plus chemotherapy plus anti–vascular endothelial growth factor drugs. This article will review landmark studies that have led to U.S. Food and Drug Administration approval of immunotherapy agents alone or in combination with chemotherapy or other immunotherapy drugs to treat advanced non–small cell lung cancer.

scholarly journals Impact of age on the toxicity of immune checkpoint inhibition

2020 ◽  
Vol 8 (2) ◽  
pp. e000871
Author(s):  
Amit Samani ◽  
Shuai Zhang ◽  
Laura Spiers ◽  
Ali Abdulnabi Mohamed ◽  
Sophie Merrick ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Inhibitor Therapy ◽  
Age Cohorts ◽  
Appreciable Increase ◽  
Treatment Type ◽  
Significant Difference ◽  
Checkpoint Inhibitor Therapy

Indications for immune checkpoint inhibitor therapy are increasing. As the population ages, many patients receiving such drugs will be older adults. Such patients are under-represented in clinical trials, and therefore the safety of immune checkpoint inhibitors in this population has not been adequately assessed. A retrospective multicenter analysis of toxicities was performed in patients with advanced or metastatic solid cancers receiving anti-programmed cell death protein 1 (anti-PD-1) and/or anti-CTLA4 antibodies across three age cohorts (<65 years, 65–74 years and ≥75 years) using univariable and multivariable analyzes. Eligible patients (n=448) were divided into age cohorts: <65 years (n=185), 65–74 years (n=154) and ≥75 years (n=109). Fewer patients in the oldest cohort (7.3%) received an anti-CTLA4 antibody containing regimen compared with the younger cohorts (21.1% and 17.5%). There was no significant difference overall in all grade or ≥G3 toxicities between age cohorts. Significantly fewer patients in the older (65–74 years and ≥75 years) age cohorts discontinued treatment because of toxicity (10.1% and 7.4%) compared with in the <65 years cohort (20.5%; p=0.006). Using logistic regression, only treatment type (ipilimumab containing) was significantly associated with all grade toxicity. However, there was a significantly lower incidence of all-grade endocrine toxicity in the oldest cohort (11.0%) compared with the youngest cohort (22.7%, p=0.02; OR 0.43, 95% CI 0.21 to 0.87), while all-grade dermatological toxicity showed the reverse trend (28.4% vs 18.9%; OR 1.85, 95% CI 1.04 to 3.30). Results were corroborated in the sensitivity analysis using only data from patients who received PD-1 inhibitor monotherapy. This multicenter, real-world cohort demonstrates that immune checkpoint inhibitor therapy is safe and well tolerated regardless of age, with no appreciable increase in adverse events in older adult patients.

scholarly journals Cytokine-Coding Oncolytic Adenovirus TILT-123 Is Safe, Selective, and Effective as a Single Agent and in Combination with Immune Checkpoint Inhibitor Anti-PD-1

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 246
Author(s):  
Riikka Havunen ◽  
Riikka Kalliokoski ◽  
Mikko Siurala ◽  
Suvi Sorsa ◽  
João M. Santos ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Immune Cell ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Interleukin 2 ◽  
Oncolytic Adenovirus ◽  
Oncolytic Viruses

Oncolytic viruses provide a biologically multi-faceted treatment option for patients who cannot be cured with currently available treatment options. We constructed an oncolytic adenovirus, TILT-123, to support T-cell therapies and immune checkpoint inhibitors in solid tumors. Adenoviruses are immunogenic by nature, are easy to produce in large quantities, and can carry relatively large transgenes. They are the most commonly used gene therapy vectors and are well tolerated in patients. TILT-123 expresses two potent cytokines, tumor necrosis factor alpha and interleukin-2, to stimulate especially the T-cell compartment in the tumor microenvironment. Before entering clinical studies, the safety and biodistribution of TILT-123 was studied in Syrian hamsters and in mice. The results show that TILT-123 is safe in animals as monotherapy and in combination with an immune checkpoint inhibitor anti-PD-1. The virus treatment induces acute changes in circulating immune cell compartments, but the levels return to normal by the middle of the treatment period. The virus is rapidly cleared from healthy tissues, and it does not cause damage to vital organs. The results support the initiation of a phase 1 dose-escalation trial, where melanoma patients receiving a tumor-infiltrating lymphocyte therapy are treated with TILT-123 (NCT04217473).

Characteristics of hospitalizations among patients receiving immune checkpoint inhibitors at a community teaching hospital

2019 ◽  
Vol 26 (1) ◽  
pp. 60-66
Author(s):  
Brendan Rasor ◽  
Rachel Henderson ◽  
Kin Chan
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Cancer Type ◽  
Preventable Admissions ◽  
The Impact ◽  
Reason For Admission

Purpose As immune checkpoint inhibitors continue to acquire new indications, it is important to understand the impact their use has on patients. This study adds to current literature by presenting an analysis of hospitalizations in this population. The primary objective was to assess the reasons for an emergency department visit or hospital admission in patients who receive immune checkpoint inhibitors. Secondary objectives included identifying the frequency of suspected or confirmed immune related adverse events, types of immune related adverse events, number of preventable admissions, duration of immunotherapy, and length of stay. Methods This study was a retrospective, multi-center, chart review of patients hospitalized after receiving an immune checkpoint inhibitor. The population included patients aged 18 and above who received at least one dose of an immune checkpoint inhibitor at a network facility and had a documented admission within one year following the initiation of immunotherapy. Descriptive statistics were performed along with inferential comparisons and a Poisson regression to determine if the immune checkpoint blocker or cancer type predicted admission or reason for admission. Results The 99 patients who met inclusion criteria had a total of 202 admissions. Of these patients, 56 (56.6%) had multiple admissions within the year following initiation of immunotherapy. The most common diagnoses on initial admissions were shortness of breath, pain, and pneumonia. A total of 104 admissions (51.5%) were considered potentially preventable. Suspected or confirmed immune related adverse events were identified in 15.6% of all admissions. There were no significant predictors of admissions or reason for admission. Conclusion Reasons for admission in the study population were comparable to those identified in the general cancer population, with immune related adverse events being associated with a minority of both total and potentially preventable admissions.

scholarly journals Neoadjuvant Immunotherapy for Muscle-Invasive Bladder Cancer

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 769
Author(s):  
Arthur Peyrottes ◽  
Idir Ouzaid ◽  
Gianluigi Califano ◽  
Jean-Francois Hermieu ◽  
Evanguelos Xylinas
Keyword(s):  
Bladder Cancer ◽  
Clinical Trials ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Response Rate ◽  
Checkpoint Inhibitor ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Neoadjuvant Immunotherapy ◽  
Muscle Invasive

Background and Objectives: Facing neoadjuvant chemotherapy followed by surgery, neoadjuvant immunotherapy is an innovative concept in localized muscle-invasive bladder cancer. Herein, we performed a review of the available and ongoing evidence supporting immune checkpoint inhibitor (ICI) administration in the early stages of bladder cancer treatment. Materials and Methods: A literature search was performed on Medline and clinical trials databases, using the terms: “bladder cancer” OR “urothelial carcinoma”, AND “neoadjuvant immunotherapy” OR “preoperative immunotherapy”. We restricted our investigations to prospective clinical trials evaluating anti-PD-(L)1 and anti-CTLA-4 monoclonal antibodies. Data on efficacy, toxicity and potential biomarkers of response were retrieved. Results: The search identified 6 ICIs that were tested in the neoadjuvant setting for localized bladder cancer—4 anti-PD-(L)1 inhibitors (Pembrolizumab, Atezolizumab, Nivolumab and Durvalumab) and 2 anti-CTLA-4 inhibitors (Ipilimumab and Tremelimumab). Most of the existing literature was based on single-arm phase 2 clinical trials that included from 23 to 143 patients. The pathological complete response rate (pCR) and pathological response rate (pRR) ranged from 31% to 46% and from 55.9% to 66%, respectively. Survival data were immature at this time. The safety profile was acceptable, with severe treatment-related adverse events ranging from 6% to 41%. Conclusions: The results of early phase trials are encouraging, and more investigations are needed to strengthen the rationale for immune checkpoint inhibitor administration in localized muscle-invasive bladder cancer.

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