Stevens-Johnson syndrome/toxic epidermal necrolysis in patients treated with immune checkpoint inhibitors: A safety analysis of clinical trials and FDA pharmacovigilance database

Background:The introduction of Immune Checkpoint Inhibitors in the recent years has resulted in high response rates and extended survival in patients with metastatic/advanced malignancies. Their mechanism of action is the indirect activation of cytotoxic T-cells through the blockade of inhibitory receptors of immunomodulatory pathways, such as cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Despite their impressive therapeutic results, they can also induce immune-related toxicity, affecting various organs, including the skin.Objective:To provide an updated summarized overview of the most common immune-mediated cutaneous side effects and their management.Method:English articles derived from the databases PubMed and SCOPUS and published between 2009 and 2018, were analyzed for this narrative review.Results:The most common adverse cutaneous reactions include maculopapular rash, lichenoid reactions, vitiligo and pruritus, with severity Grade 1 or 2. Less frequent but eventually life-threatening skin side effects, including Stevens-Johnson syndrome, Drug Reaction with Eosinophilia and Systemic Symptoms and Toxic Epidermal necrolysis, have also been reported.Conclusion:Basic knowledge of the Immune-Checkpoint-Inhibitors-induced skin toxicity is necessary in order to recognize these treatment-related complications. The most frequent skin side effects, such as maculopapular rash, vitiligo and pruritus, tend to subside under symptomatic treatment so that permanent discontinuation of therapy is not commonly necessary. In the case of life-threatening side effects, apart from the necessary symptomatic treatment, the immunotherapy should be permanently stopped. Information concerning the management of ICIs-mediated skin toxicity can be obtained from the literature as well as from the Summary of Product Characteristics of each agent.

Download Full-text

Immune checkpoint inhibitors for patients with lung cancer and IPF: Specific clinical trials needed

European Journal of Cancer ◽

10.1016/j.ejca.2021.04.001 ◽

2021 ◽

Author(s):

Boris Duchemann ◽

Johan Pluvy ◽

Bruno Crestani ◽

Gérard Zalcman ◽

Hilario Nunes

Keyword(s):

Lung Cancer ◽

Clinical Trials ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors

Download Full-text

Cardiotoxicity of immune checkpoint inhibitors: A systematic review and meta-analysis of randomised clinical trials

European Journal of Cancer ◽

10.1016/j.ejca.2021.01.043 ◽

2021 ◽

Vol 148 ◽

pp. 76-91

Author(s):

Elisa Agostinetto ◽

Daniel Eiger ◽

Matteo Lambertini ◽

Marcello Ceppi ◽

Marco Bruzzone ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Randomised Clinical Trials

Download Full-text

New drug developments in metastatic gastric cancer

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284818808072 ◽

2018 ◽

Vol 11 ◽

pp. 175628481880807 ◽

Cited By ~ 6

Author(s):

Aaron C. Tan ◽

David L. Chan ◽

Wasek Faisal ◽

Nick Pavlakis

Keyword(s):

Gastric Cancer ◽

Clinical Trials ◽

Targeted Therapies ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Treatment Options ◽

Predictive Biomarkers ◽

Metastatic Gastric Cancer ◽

New Era

Metastatic gastric cancer is associated with a poor prognosis and novel treatment options are desperately needed. The development of targeted therapies heralded a new era for the management of metastatic gastric cancer, however results from clinical trials of numerous targeted agents have been mixed. The advent of immune checkpoint inhibitors has yielded similar promise and results from early trials are encouraging. This review provides an overview of the systemic treatment options evaluated in metastatic gastric cancer, with a focus on recent evidence from clinical trials for targeted therapies and immune checkpoint inhibitors. The failure to identify appropriate predictive biomarkers has hampered the success of many targeted therapies in gastric cancer, and a deeper understanding of specific molecular subtypes and genomic alterations may allow for more precision in the application of novel therapies. Identifying appropriate biomarkers for patient selection is essential for future clinical trials, for the most effective use of novel agents and in combination approaches to account for growing complexity of treatment options.

Download Full-text

Combinatorial benefit without synergy in recent clinical trials of immune checkpoint inhibitors

10.1101/2020.01.31.20019604 ◽

2020 ◽

Cited By ~ 1

Author(s):

Adam C. Palmer ◽

Benjamin Izar ◽

Peter K. Sorger

Keyword(s):

Clinical Trials ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Single Agent ◽

Combination Therapies ◽

Anti Tumor Activity

ABSTRACTHundreds of clinical trials are testing whether combination therapies can increase the anti-tumor activity of Immune Checkpoint Inhibitors (ICIs). We find that the benefits of recently reported and approved combinations involving ICIs are fully accounted for by increasing the chance of a single-agent response (drug independence), with no requirement for additive or synergistic efficacy. Thus, the degree of success of combinations involving ICIs with other therapies is largely predictable.

Download Full-text

Speed of Adoption of Immune Checkpoint Inhibitors of Programmed Cell Death 1 Protein and Comparison of Patient Ages in Clinical Practice vs Pivotal Clinical Trials

JAMA Oncology ◽

10.1001/jamaoncol.2018.0798 ◽

2018 ◽

Vol 4 (8) ◽

pp. e180798 ◽

Cited By ~ 34

Author(s):

Jeremy M. O’Connor ◽

Kristen L. Fessele ◽

Jean Steiner ◽

Kathi Seidl-Rathkopf ◽

Kenneth R. Carson ◽

...

Keyword(s):

Clinical Trials ◽

Cell Death ◽

Clinical Practice ◽

Programmed Cell Death ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Programmed Cell Death 1

Download Full-text

Immune Checkpoint Inhibitors as Monotherapy or Within a Combinatorial Strategy in Advanced Hepatocellular Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms21176302 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6302

Author(s):

Michela Guardascione ◽

Giuseppe Toffoli

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trials ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Kinase Inhibitors ◽

Checkpoint Inhibitors ◽

Target Therapy ◽

Antiangiogenic Agents ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Hcc

In advanced-stage hepatocellular carcinoma (HCC), systemic treatment represents the standard therapy. Target therapy has marked a new era based on a greater knowledge of molecular disease signaling. Nonetheless, survival outcomes and long-term response remain unsatisfactory, mostly because of the onset of primary or acquired resistance. More recently, results from clinical trials with immune targeting agents, such as the immune checkpoint inhibitors (ICIs), have shown a promising role for these drugs in the treatment of advanced HCC. In the context of an intrinsic tolerogenic liver environment, since HCC-induced immune tolerance, it is supported by multiple immunosuppressive mechanisms and several clinical trials are now underway to evaluate ICI-based combinations, including their associations with antiangiogenic agents or multikinase kinase inhibitors and multiple ICIs combinations. In this review, we will first discuss the basic principles of hepatic immunogenic tolerance and the evasive mechanism of antitumor immunity in HCC; furthermore we will elucidate the consistent biological rationale for immunotherapy in HCC even in the presence of an intrinsic tolerogenic environment. Subsequently, we will critically report and discuss current literature on ICIs in the treatment of advanced HCC, including a focus on the currently explored combinatorial strategies and their rationales. Finally, we will consider both challenges and future directions in this field.

Download Full-text